Appropriate Antithrombotic Management for Older Adults Living with Dementia

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

1) It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard orginal research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

2) It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

3) Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

4) The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

And Some minor adjustments: 

Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is slef explanatory. 

Exclusion criteria :psychiatric or neurological problems that caused cognitivechanges not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, Etoh or other substances? 

Please specify the timing of the questionnaires in the methods section. Where thay performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission? 

 

 

 

 

 

Author Response

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.

My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24 hour care at home etc)

Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

A conclusion section is completely missing.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

Author Response

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

Dear Editor and Reviewers,

 

Thank you for the very helpful review of our manuscript entitled Appropriate Anticoagulant Management for Older Adults Living with Dementia and the opportunity to revise and resubmit this for continued review.  We changed the title to use the term antithrombotic instead of anticoagulant as per the reviewer recommendation thus the new title is Appropriate Antithrombotic Management for Older Adults Living with Dementia.  Our responses to the queries are noted below. 

Reviewer 1:

Reviewer:  This is a nice work on a very important topic. I can see that a lot of effort went into collecting valuable data regarding the use of antiplatelets in elderly patients who had a recent admission. I personally found the introduction very lengthy for an original research manuscript, but for some, it might be helpful as it serves as a mini literature review. My main concern is that the manuscript struggles to find a clear objective and a clear message. Some of the thoughts that this work generated which may help reshape it are given below, with my full respect and admiration to the writers for their herculean task. 

RESPONSE:  We did not shorten the introduction as it is review particularly for those that maybe less familiar with antithrombotic treatment recommendations and issues.  We clarified that the purpose of the paper is to provide descriptive information about use of antithrombotics in a sample of older adults living with dementia who go through care transitions from hospital to 1 month post hospitalizations. 

…. To get a sense of the current use of antithrombotics among older adults living with dementia during care transitions we evaluated use of these medications from admission to acute care to one month post discharge.   Specifically, the percentage of individuals on antithrombotics, the number of antithrombotics prescribed, and evidence of associated bleeding with treatment on admission and at one month post discharge were evaluated.  The findings from this study can be used to guide approaches for determining antithrombotic treatment among older adults living with dementia.  

REVIEWER:  It is great to consider what are the risk factors associated with bleeding:  It would be great if table 1 was a table with all the comorbidities of the included patients like a standard original research study. That way the reader could appreciate if this sample had a lot of those risk factors that we should consider before freely giving multiple antiplatelets

RESPONSE:  We remade Table 1 (based also on recommendations noted below about the lack of need for the description of the CHAD₂DS₂-VASc.  The revised Table 1 provides all the comorbidities of the participants. 

REVIEWER:  It would be great to know why those patients were admitted in the first place. That could also prevent biases having to do with overestimating the prevalence of dementia if some of the symptoms could be tied to acute illness. 

RESPONSE:  The admission diagnoses are so variable it is not even appropriate to try and group them together.  We have, however, included in the text a description of some of the admission diagnoses to give a sense of the range of these.  These are described as follows:   

…. Admission diagnoses varied significantly across the sample including such things as abdominal pain, abnormal labs, a jaw fracture, a change in function, anemia, change in cognition, cystitis, diarrhea, congestive heart failure, pneumonia or other infections, renal failure, respiratory failure, fever, weakness, among others.

REVIEWER:  Another suggestion is to perform a chi-square test for comparing percentages between the groups (dementia - no dementia, Antiplatelets or no), but I understand that this is not the scope of the paper. 

REPONSE:  As noted above the focus of the paper was to describe the use of antithrombotics among older adults living with dementia and experiencing care transition between the hospital and 1 month post discharge.  All of the participants had dementia (this was one of the criteria for participation) and the Saint Louis University Mental Status exam indicated that they all had moderate to severe dementia. Consequently, it was impossible to compare those with and without dementia.  Nor was the focus to compare those who were or were not on antiplatelets.

REVIEWER:  The first point of the discussion is that antiplatelet agent use is similar to other studies and dropped to 60% after one month but still high. What is the objective of the study? Should this percentage be lower? Do we know what was the indication that the patients were taking them for ? Do we know how many cardiovascular events they were saved from due to the fact that they were on an antiplatelet ? Without analyzing the indications or the reason for admission, we cant say much regarding the decision to prescribe one. It would be significant if using the data that you collected + some additional baseline demographics, to deduce whether prescribing so many antiplatelets in this delicate population of patients should be done with a lot of caution. 

RESPONSE:  The purpose of this paper was simply to describe the use of antithrombotics in this population of older hospitalized patients living with dementia. We used data from the parent study, Testing the Effectiveness of the FFC-AC-EIT intervention which was focused on increasing physical activity among hospitalized older adults.  While we obtained medications prescribed there was no rationale for why each was given by a provider.  The admission diagnoses are very varied although we have now described in them in the text and the comorbidities are all listed in Table 1.  It would be purely conjecture to assume that an antithrombotic should be described given these details. Other things need to be considered such as risk of falls and patient goals of care. Thus, our conclusion is that shared decision making should be done to make these decisions.  

REVIEWER:  Table 1. Congestive Heart Failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled),Vascular Disease, Age 65 To 74 And Sex Category (Female) (CHA2DS2-VASc) Scores.==> this is the legend for table 1 which in fact is the CHA2DS2- VASc  ==>  Maybe the authors can use table one for a better purpose. Or maybe change the legend to something more informative as the table is self explanatory. 

RESPONSE:  As noted above we changed Table 1 which now provides comorbidities.

REVIEWER:  Exclusion criteria: psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.==> How about electrolyte abnormalities, sepsis, acidosis, ETOH or other substances? 

RESPONSE:  AS per the focus of the parent study our inclusion criteria were used to identify dementia based on a rigorous process that included four measures.  We agree and appreciate that medical situations could cause some acute delirium with cognitive changes. Our measures however included informant (legally authorized representative) input and were focused on the time period prior to the acute event.  As described in the paper our eligibility requirements for cognitive status were as follows:

… Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis University Mental Status Examination 21 completed by the participant, and the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview22 based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale 23; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between de-mentia and mild cognitive impairment 24. 

 

REVIEWER:  Please specify the timing of the questionnaires in the methods section. Where they performed early on during the admission? Acute phase? Could it be that some patients had reversible causes of their symptoms due to acute illness on admission?

RESPONSE:  We clarified the timing of the assessments and as noted above our evaluation of the patient’s dementia was not just based on admission findings.  The clarification of assessment timing is now described as follows:

…. Data was collected by research evaluators based on chart review within the first 48 hours of admission to the hospital unit and via telephone follow up at one month post discharge from the patient's caregiver/legally authorized representative.  In addition, any adverse events including falls, emergency room transfers, hospital admissions and death were obtained during the telephone follow up. 

Reviewer 2:

REVIEWER:  The authors performed a very interesting study about the baseline characteristics and one-month outcome after discharge from hospital in older patients with dementia in relation to their anticoagulant use. They found that a proportion of patients suffered from complications from anticoagulation therapy and antithrombotic therapy was not reduced from admission to one-month follow up, probably due to shared decision making.  My major concern with the study is that details about the recruitment are not documented. Was the study approved by the ethics committee? (Which approval number?) Had the patients signed informed consent before inclusion? Were patients with dementia eligible to sign informed consent? How many patients screened were included in the study? How was follow up carried out? The authors write at the beginning of the results section that only “the first 404” patients “with medication data at admission” were included – how many patients with a missing medication list were excluded?

RESPONSE:  We have clarified that this study was reviewed by the University of Maryland Institutional Review Board and all participants/or legally authorized representatives consented to participated.  The process for recruitment is delineated as follows:

… This was a descriptive study using baseline data and one month follow up data from the study, Testing the Implementation of Function Focused Care in Hospitalized Older Adults Living with Dementia (R01AG065338; Clinicaltrials.gov NCT04235374). The study was reviewed and approved by the University of Maryland Institutional Review Board.   To participate, hospitals had to have a unit dedicated to medical patients. Patients were eligible to participate if they were 55 years of age or older, were admitted with a medical diagnosis,  screened positive for dementia based on a score of < 20 on the Saint Louis Universi-ty Mental Status Examination completed by the participant, and completion of the following three measures based on input from the legally authorized representative: a score of > 2 on the AD8 Dementia Screening Interview based on input from the legally authorized representative; a score of 0.5 to 2.0 on the Clinical Dementia Rating Scale; and a score of ≥ 9 on the Functional Activities Questionnaire to differentiate between dementia and mild cognitive impairment.  Patients were excluded if they were enrolled in Hospice, on the unit for more than 48 hours, had no contact noted to provide follow up information, required surgery, or had a psychiatric or neurological problems that caused cognitive changes not due to dementia such as a brain tumor.   All potentially eligible patients were approached about the study and completed an Evaluation to Sign Consent.  The Evaluation to Sign Consent includes 5 items that ask potential participants such things as what they would be expected to do if participating in the study, and what to do if they wanted to stop participating.  If the individual did not pass the Evaluation to Sign Consent, assent was obtained to contact their legally authorized representative and proceed with the consenting process. A total of 6,471 patients were screened with ineligibility being due to having COVID-19, discharged or not available to be approached, the patient was non-communicative and could not even assent, not being eligible based on criteria, or refusals by patient or legally authorized representative.  A total of 404 patients were recruited.

REVIEWER:  The authors write that adverse events due to antithrombotic therapy were more common in patients with antithrombotic therapy. Was there no bleeding in patients without anticoagulation? Please compare “bleeding” with “bleeding” (and “stroke” with “stroke”).

RESPONSE:  The statement about antithrombotic therapy being associated with more adverse events was noted in the introduction from prior studies.  In fact, as described in our findings the majority of the adverse events we would expect from antithrombotic use were not among those on antithrombotics.  Specifically, our results showed the following:

For admission events:

… Among the 280 participants on antithrombotics there were 12 individuals (4%) that were admitted due to a complication associated with antithrombotic (evidence of bleeding based on a head trauma, evidence of blood in stool, or anemia).  Only 4 (33%) out of the 12 individuals admitted with bleeding related events were on antithrombotics.

At 1 month post discharge

…  At one month post discharge there were 5 (1%) individuals who had complications from antithrombotic therapy.    As with admission complications associated with antithrombotics, complications at 1 month were based evidence of gastrointestinal bleed and head trauma. Only 2 (40%) out of the 5 individuals were on antithrombotics.    

REVIEWER:  I think that sufficient care for patients with dementia is very important. Can the authors add data about the type of care in discharged patients? (Nursing home, 24-hour care at home etc.)

RESPONSE: We provided the discharge locations for participants for descriptive purposes.  The text now includes the following:

…   Discharge location also varied with 188 (47%) living in home settings (with a caregiver), 25(6%) living in assisted living, 181(45%) in nursing homes or subacute settings, 5 (1%) died and 3(1%) went to acute rehabilitation settings, and 2(1%) were unknown locations.

REVIEWER:  Please use the term “antithrombotic therapy” when referring to both anticoagulants and antiplatelets.

RESPONSE:  We revised the paper to use antithrombotic throughout unless referring to specific drug groups or drugs.

REVIEWER:  A conclusion section is completely missing.

RESPONSE: We added both a study strengths and limitations section and conclusion section.  These read as follows:

Study Strengths and Limitations

            A strength of this study was the large sample of older adults living with dementia from across 10 hospitals.  This was a secondary data analysis using data from the first 404 participants in the parent study thus detailed data such as the reasons providers had individuals on antithrombotics, the reasons for continuing them at discharge, or discontinuing them were not obtained.  Likewise, the one month follow up data for adverse events was based on recall of the legally authorized representatives and not hospital records and documentation of the actual cause of the readmission and if it was related to anticoagulant use. Further we do not know the number of events that may have been prevented if individuals were on antithrombotics (e.g., strokes, blood clots). 

Conclusion

The findings from this study indicate that there is still a high rate of antithrombotic use among older adults living with dementia.  We noted there are some risks for use based on causes for hospital admission and readmission during the first month post discharge. Guidance for antithrombotic use among older adults, particularly those living with dementia and those greater than 90 years of age is vague and the recommendation suggests the use of "careful consideration" when making treatment decisions.  In situations in which there are not clear data to guide practice such as what we have seen with regard to some immunizations, a shared decision making and a person-centered approach may be the most ap-propriate way to proceed. Person-centered care is focused on engaging the individual or their legally authorized representative in shared decision making around a care related topic.  Helping older adults living with dementia and their legally authorized representatives understand the benefits and risks associated with antithrombotic use and identifying their goals of care, can help these individuals establish what risk they are willing to take.  Documentation of this discussion and ongoing evaluation of the use of antithrombotics should also be done.  With increased opportunities for treatment in terms of number and types of drugs available, our understanding of the risk and benefits associated with antithrombotics will develop as new data is accrued.  For now, the person-centered shared decision-making approach may be the safest and most appropriate way to address antithrombotic use among older adults living with dementia.

Minor comments:

• Please summarize major details about Methods and Results in the first sentence of the discussion.
• Use a unit for age in the abstract (probably “years”)
• Current guidelines recommend the CHADS-VA score instead of the CHADS-VASc score. Please revise.
• The CHADS-VASc score is written wrongly in Table 1: stroke leads to two points.
• Results: Please report percentages rather than absolute numbers – same for tables (especially Tables 4, 5)

 

 

 

 

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for addressing the comments.