Prevalence and Risk Factors of Neuropsychiatric Symptoms in Institutionalized Patients with Parkinson’s Disease in Taiwan: A Nationwide Observational Study

Round 1

Reviewer 1 Report

The paper is very interesting, article concerning the presence of neuro psychiatric symptoms in patients with Parkinson’s disease.

Authors focused their attention on institutionalized patients.

The topic is very interesting because the presence of psychiatric symptoms may complicate the course of the disease and require pharmacological modifications. In addition there is an increased burden on caregivers.

The authors conducted a cross-sectional study in more than twenty counties. They considered nearly 400 patients.

The authors used Mini Mental State Examination, activities of daily living, and Instrumental activities of daily living to assess the presence of cognitive impairment and physical impairment.

Hoen and Yahr's scale to assess Parkinson's disease disability.

Authors described three important neuropsychiatric symptoms: nigh time behaviour, depression, fear/anxiety.

They found that genito urinary disease and psychiatric disorders can increase the risk of neuro psychiatric disease.

I believe that some aspects could be modified before publication.

Abstract has a fair length and describes the work, however, I think it is better to rephrase line 26-27, where the presence of “two groups” is indicated, specifying which ones are.

Table 2 lack of caption; the term BPS, which is not present in the text.

In table 2 there are three lines separating the items.

Table 3 lack of caption.

In the discussion, Authors identified that neuropsychiatric disorders and urinary disorders may increase the risk of psychiatric symptoms. I think it is useful to interpretate these data and compare them with the literature.

The conclusions are too brief.

Author Response

1. Abstract has a fair length and describes the work, however, I think it is better to rephrase line 26-27, where the presence of “two groups” is indicated, specifying which ones are.

Answer: Thank you for the comment. We have rephrased the description in line 26-27 "..the two groups..." to "..those with NPS and those without NPS".

2. Table 2 lack of caption; the term BPS, which is not present in the text.

Answer: Thank you for the comment. We have added caption of Table 2 with "Prevalence and frequency of each NPS type in all PD patients" and changed the wrong description in the table "BPS" to "NPS".

3. In table 2 there are three lines separating the items.

Answer: Thank you for the comment. We have removed the three lines.

Table 3 lack of caption.

Answer: Thank you for the comment. We have added the caption of Table 3 with "Association of PD severities and MMSE, NPS, IADL, and ADL".

4. In the discussion, the Authors identified that neuropsychiatric disorders and urinary disorders may increase the risk of psychiatric symptoms. I think it is useful to interpret these data and compare them with the literature.

Answer: Thank you for the comment. We have added discussion below:

"We also found some possible risk factors for NPSs ...As expected, genitourinary disease and psychiatric problems may contribute to NPSs. The association of previous psychiatric problems with NPS was in line with previous studies. Indeed, co morbid sleep disturbances and anxiety disorder were found be associated with the risk of depression in PD [26]. Dissanayaka et al. found that self history of psychiatric disturbances may significantly increase the risk of anxiety disorders in PD [27]. Leetjens et al. reported non-specific factors in a cross-sectional study, including female gender, history of anxiety and/or depression, and worse cognitive status, may be significantly associated with depression in PD [28]. We did not further clarify the psychiatric problem to a specific domain of NPSs. Future study could be focused on finding the association between psychiatric problems and specific NPSs, in addition to depression and anxiety. Genitourinary disease were also common in PD. Previous studies concerning the impact of genitourinary disease on NPS were few. Rana et al. reported neurogenic lower urinary tract dysfunction may increase the risk of anxiety and depression in PD [29]. We did not collect the information of specific genitourinary disease in each patient, and further study may be warranted to validate our findings."

5. The conclusions are too brief.

Answer: Thank you for the comment. We have rephrased the conclusion in the manuscript with the paragraph below: 

" In conclusion, for the first time, we showed the prevalence of NPS in institutionalized Taiwanese PD patients. High rates of NPSs and physical restraints emphasized the need for recognition and treating NPSs in PD patients which can lead to the improvement of their quality of life. Our study also suggests that previous history of psychiatric, genitourinary disease may be associated with a higher risk of NPS. Factors associated with this positive association are unclear and warrant future research."

Reviewer 2 Report

This manuscript is well written.

'but reports about the prevalence in institution are little'... this description is not clear. It becomes clearer while reading the manuscript, but it's better if the authors can define it in the abstract. Also, I understand there is little report on this, but why it is important to study this?  The authors need to highlight why their study is important.

... placement in nursing homes [1,8]. Furthermore, ... '.' was missing

'Table 2. This is a table. Tables should be placed in the main text near to the first time they are cited.' Please give a proper title for table 2. Also table 3.

Table 2 frequency of BPH, why the cut off was defined to be 3?

Author Response

1.'but reports about the prevalence in institutions are little'... this description is not clear. It becomes clearer while reading the manuscript, but it's better if the authors can define it in the abstract.

Answer: Thank you for the comment. We have added a description below: "Neuropsychiatric symptoms (NPSs) are known to be frequent in Parkinson's disease (PD) with great impact on the quality of life, but reports about the prevalence in institution are little." 

2. Also, I understand there is little report on this, but why it is important to study this?  The authors need to highlight why their study is important.

Answer: Thank you for the comment.  We have added descriptions below: " A better understanding of the prevalence and essential profiles of NPSs may be helpful for patients with PD and their caregivers in order to improve the quality of life and reduce the caregiver’s burden Furthermore, the information may provide the reference to the policy of long-term care.

3. ... placement in nursing homes [1,8]. Furthermore, ... '.' was missing

Answer: Thank you for the comment.  We have added "." after [1,8].

4. 'Table 2. This is a table. Tables should be placed in the main text near to the first time they are cited.' Please give a proper title for table 2. Also table 3.

Answer: Thank you for the comment. We have added proper title to table 2 and table 3. 

5. Table 2 frequency of BPH, why the cut off was defined to be 3?

Answer: Thank you for the comment. The frequency of NPS would be recorded according to the survey. We did not set the cut-off value to 3. 

Reviewer 3 Report

In the abstract, should be "reports about the prevalence in institutions are few." Also, you mention differences "between the two groups" but it is not clear what two groups these are--those with and those without NPS? Please clarify.  When you state that "genitourinary disease....and psychiatric disorders...may increase the risk of NPSs" there are two major problems.  First, this implies cause and effect.  You have not shown that.  It is an association, and it would be best to state that these problems have a significant *association with* NPS.  Second, to state that psychiatric disorders are associated with a higher risk of neuropsychiatric symptoms is not helpful information unless you show that these are PD-specific and unrelated to the primary psychiatric disorder.  Beyond this, I am unsure why the statement in lines 75-76 about not involving patients and community in the study design is needed. Is this a regulatory issue? As far as dissemination, it is usually sufficient to say that the study adhered to patient privacy regulations.  On line 81, were neurologists and psychiatrists randomly assigned to examine and interview the patients, or were neurologists and psychiatrists assigned based on the diagnosis or symptoms? These two specialties might be expected to conduct rather different examinations.  On line 116, and Table 1, the need for physical restraints should be explained: was this for violent behavior toward staff? Risk of self harm? Or simply to prevent the patient from falls or from leaving their rooms? These all have very different implications. Several of these behaviors are noted in Table 2.  Please also note that the titles for Table 2 and Table 3 are just placeholder language, and the actual title of the Table has not been inserted. Line 175 should be "what is worthy of notice is that we observed...." and here again the reason for the restraints would be important to note.

Author Response

1.In the abstract, should be "reports about the prevalence in institutions are few.

Answer: Thank you for the comment. We have changed to sentence according to your description.

Also, you mention differences "between the two groups" but it is not clear what two groups these are--those with and those without NPS? Please clarify.  

Answer: Thank you for the comment. We have 

When you state that "genitourinary disease....and psychiatric disorders...may increase the risk of NPSs" there are two major problems.  First, this implies cause and effect.  You have not shown that.  It is an association, and it would be best to state that these problems have a significant *association with* NPS.  

Answer: Thank you for the comment. We have changed the description below: 

"multivariate logistic regression analysis showed that genitourinary disease (odds ratio (OR)=3.13; 95% confidence interval (95%CI) =1.77–5.51) and psychiatric disorders (OR=5.18; 95%CI=3.09–8.69) may be associated with increased risk of NPSs." 

3. Second, to state that psychiatric disorders are associated with a higher risk of neuropsychiatric symptoms is not helpful information unless you show that these are PD-specific and unrelated to the primary psychiatric disorder.  

Answer: Thank you for the comment. Psychiatric disorders like anxiety and depression may be cor morbid diseases to each other. However, it would be difficult to define PD-specific depression in a large national survey. We believe it would a good suggestion to do further research in the hospital-based cohort.

4. Beyond this, I am unsure why the statement in lines 75-76 about not involving patients and the community in the study design is needed. Is this a regulatory issue? As far as dissemination, it is usually sufficient to say that the study adhered to patient privacy regulations. 

Answer: Thank you for the comment. The national survey is initiated by Taiwan National Health Research Institute to do a cross-sectional, community-based, observational study in residential long-term care service institutions. We have changed the description below: "All the interviewers or specialists participated in a training course before the survey to achieve a consensus and reduce inter-individual bias in evaluation. The study adhered to patient privacy regulations. "

5 On line 81, were neurologists and psychiatrists randomly assigned to examine and interview the patients, or were neurologists and psychiatrists assigned based on the diagnosis or symptoms? These two specialties might be expected to conduct rather different examinations.  

Answer: Thank you for the comment. We recruited volunteer doctors to join the survey and we did not assign neurologists and psychiatrists to examine based on the diagnosis or symptoms. 

6. On line 116, and Table 1, the need for physical restraints should be explained: was this for violent behavior toward staff? Risk of self-harm? Or simply to prevent the patient from falls or from leaving their rooms? These all have very different implications.

Answer: Thank you for the comments. We did not record the purpose of physical restraints in our study. It would a good suggestion for us to re-design our questionnaire in future studies.

7. Several of these behaviors are noted in Table 2.  Please also note that the titles for Table 2 and Table 3 are just placeholder language, and the actual title of the Table has not been inserted.

Answer: Thank you for the comment. We have added proper titles to table 2 and table 3. 

8. Line 175 should be "what is worthy of notice is that we observed...." and here again the reason for the restraints would be important to note.

Answer: Thank you for the comment. We have changed the sentence to "what is worthy of notice is that we observed...." . We did not record the purpose of physical restraints and we list the limitations as below: " Whether these patients had REM sleep behavior disorder (RBD),... gold standard polysomnography data. Lastly, we did not define the purpose to do physical restraints in our study and our findings should be read with caution. It warrants further study to know the implications."