Prevalence and Outcomes of Orthostatic Hypotension in Hemorrhagic Stroke Patients During Hospitalization
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis is an interesting and original study into the prevalence of orthostatic hypotension in hemorrhagic stroke patients during hospitalization. While the study aligns well with the scope of Neurology International, I have identified areas where clarification and improvement could enhance the manuscript's overall quality.
1. Title: Consider removing the word “outcome” from the title, as it may imply an emphasis on elements not fully addressed in this study.
2. Abstract: Clearly articulate the study's objectives in the "Background/Objectives" section, as it currently focuses solely on background. Specify the timeframe of the retrospective analysis. Minimize abbreviations to improve readability. For example, avoid abbreviating mRS since it appears only twice in the text.
3. Introduction: The introduction is well-written and provides an appropriate context. However, I recommend updating some references to include recent studies to ensure relevance and timeliness.
4. Methods: Provide detailed inclusion and exclusion criteria. Specify the variables analyzed and clarify why certain variables were excluded. Explain how informed consent was addressed, as it is a requirement even in retrospective studies. Clarify whether OH was assessed upon admission or during hospitalization. Provide more details about the two groups (with and without OH) and the variables analyzed for each. Justify the focus on hemorrhagic stroke rather than ischemic stroke. Explain why a retrospective design was chosen over a prospective approach.
5. Results: The statement regarding the inability to retrieve medication lists for 12 patients should be revisited. Should these patients be excluded from the analysis? Correct the numbering under “3.2. Figures, Tables, and Schemes.”
6. Discussion: The discussion is comprehensive, and I commend the authors for their work. Discuss in greater detail the limitations associated with conducting a retrospective analysis. Address variables that showed no significant differences between groups and provide potential explanations.
7. Conclusion: Appropriate.
8. Informed Consent Statement: Verify whether the Institutional Review Board supports the statement: “Patient consent was waived by the IRB due to the minimal risk of collecting non-sensitive data.” Emphasize that consent waivers are more about safeguarding personal information than minimizing risk.
9. References: Update older references with more recent ones to reflect the latest research in the field.
Author Response
1. Title: Consider removing the word “outcome” from the title, as it may imply an emphasis on elements not fully addressed in this study.
A 1. Thank you for your advice. Despite the limited data from the retrospective review, we have analyzed several variables relevant to clinical outcomes, such as the length of stay and the modified Rankin Scale at discharge. We kindly ask for the reviewer’s understanding that this study was conducted as preliminary research for a prospective longitudinal study.
2.1. Abstract: Clearly articulate the study's objectives in the "Background/Objectives" section, as it currently focuses solely on background.
A 2.1. Thank you for pointing this out. We have added the objective of the study in the abstract.
→ Page 1, Line 15-17: “This study aims to examine the prevalence of OH, its risk factors and potential impact in patients who were hospitalized due to hemorrhagic stroke.”
2.2. Specify the timeframe of the retrospective analysis.
A2.2. Thank you for your advice. We have now specified that a retrospective analysis of inpatient records between 1 January 2021 and 30 April 2023 was conducted (Page 1, Line 17-18).
2.3. Minimize abbreviations to improve readability. For example, avoid abbreviating mRS since it appears only twice in the text.
A 2.3. Thank you. We have removed the abbreviations for modified Rankin Scale (Page 1, Line 28) and blood pressure (Page 1, Line 20-21).
3. Introduction: The introduction is well-written and provides an appropriate context. However, I recommend updating some references to include recent studies to ensure relevance and timeliness.
A 3. Thank you for your advice. We have updated some of the references accordingly.
→ Page 1, Line 39-40: “It is highly prevalent in hospitalized patients occurring in as many as 75% in elderly population [2].
→ Page 2, Line 45: Stroke is one of the top causes of hospitalizations[5].
However, other references were retained due to the scarcity of recent studies specifically addressing OH in stroke.
4.1. Methods: Provide detailed inclusion and exclusion criteria.
A 4.1. Thank you for your advice. We have rewritten the paragraph to make the inclusion and exclusion criteria clearer.
→ Page 2, Line 74-81: “This was a retrospective analysis of consecutive patients referred to rehabilitation medicine between 1 January 2021 and 30 April 2023 at National University Hospital, Singapore. We included all patients aged 18-99, with a diagnosis of "stroke due to intracerebral hemorrhage" (ICH) or "stroke due to subarachnoid hemorrhage" (SAH) according to the American Heart Association/American Stroke Association diagnostic criteria. Exclusion criteria included absence of postural blood pressure measurements during their hospitalization, patients with hemorrhages due to trauma, tumors, or hemorrhagic transformation of an ischemic infarct.”
4.2.1. Specify the variables analyzed.
A 4.2.1. Thank you for the advice. We specified the reason for selecting the variables in “Materials and Methods” section.
→ Page 3, Line 97-105: The use of antihypertensive medications was identified as an important risk factor for OH. We documented the administration of these medications within 48 hours before the postural blood pressure assessment by reviewing patients' prescription records. Co-morbidities known to be associated with an increased risk of OH were also recorded, including hypertension, diabetes, chronic kidney disease, ischemic heart disease, prior stroke, and Parkinsonism. Functional outcomes at hospital discharge were evaluated using the modified Rankin Scale (mRS). To assess severity, hematoma volume for ICH patients was calculated using the ABC/2 formula, while the World Federation of Neurological Surgeons (WFNS) grading scale was documented for SAH patients.
4.2.2. clarify why certain variables were excluded.
A 4.2.2. Thank you for your advice. We would have preferred to include a unified initial stroke severity measurement, such as the National Institutes of Health Stroke Scale (NIHSS). However, this was not measured consistently due to the study's retrospective nature and was therefore excluded. (Page 7, Line 251-252)
4.3. Explain how informed consent was addressed, as it is a requirement even in retrospective studies.
A 4.3. Thank you for pointing this out. We have added that
→ Page 3, Line 116-120: “A waiver of consent was obtained as the study involved only collecting non-sensitive data during routine clinical care, with minimal to no risk to patients. Measures to ensure patient confidentiality were strictly implemented.”
4.4. Clarify whether OH was assessed upon admission or during hospitalization.
A 4.4. Thank you for your advice. We have clarified that postural blood pressure measurements were conducted during hospitalization. (Page 2, Line 83)
4.5. Provide more details about the two groups (with and without OH) and the variables analyzed for each.
A 4.5. Thank you for your advice. The criteria for the two groups were added.
→ Page 2, Line 86-87: “OH was defined as a drop in systolic BP of ≥20 mmHg or diastolic BP of ≥10 mmHg when compared to the supine BP.”
And
Page 2, Line 89-91: “We analyzed and compared the groups with at least one reading meeting the OH criteria during the hospital stay to those without any documented instances of OH.”
4.6. Justify the focus on hemorrhagic stroke rather than ischemic stroke.
A 4.6. Thank you. The reasons of analyzing only hemorrhagic stroke patients we
would like to mention in the introduction section.
→Page 2, Line 56-65: “there is no fully committed study regarding OH in patients with hemorrhagic stroke to describe its clinical features, identify possible contributing factors, gauge clinical impact on the outcome. Previous studies involving both ischemic and hemorrhagic strokes found no differences in OH prevalence between the two types, and OH did not impact length of stay, functional outcomes, cardiovascular risks, or mortality. However, hemorrhagic stroke data in these studies were limited. Lowering blood pressure is recommended in acute intracerebral hemorrhage, but the impact of antihypertensive use on OH incidence remains unclear. Additionally, OH is common after major surgeries, contributing to delayed mobilization, falls, and prolonged hospital stays. Therefore, OH in hemorrhagic stroke patients should be studied separately from ischemic stroke.”
4.7. Explain why a retrospective design was chosen over a prospective approach.
A 4.7. Thank you. We have specified in the introduction instead that this retrospective analysis was conducted to generate preliminary data for a prospective study”. (Page 2, Line 70-71)
5.1. Results: The statement regarding the inability to retrieve medication lists for 12 patients should be revisited. Should these patients be excluded from the analysis?
A 5.1. Thank you for your advice. We conducted a separate analysis and found that including or excluding the 12 patients did not affect the mean, median significantly for the remaining variables. Since we are not using regression analysis for these variables, we have decided to retain the 12 subjects without a medication history in our study. However we have included this in the limitation (Page 7, line 259-260: Lastly, the missing medication data of the 12 patients might affect the interpretation of effects of antihypertensives on OH.)
5.2. Correct the numbering under “3.2. Figures, Tables, and Schemes.”
A 5.2. Thank you for pointing this out. We have removed the number “3.2. Figures, Tables, and Schemes” as it is not necessary.
6.1. Discussion: The discussion is comprehensive, and I commend the authors for their work. Discuss in greater detail the limitations associated with conducting a retrospective analysis.
A 6.1. Thank you for your advice. We have added the limitation of retrospective analysis. → Page 6-7, Line 234-236: “The small sample size and the retrospective nature of our study might limit the ability to detect the interplay of risk factors”.
AND
→ Page 7, Line 255-259: “There were also significant number of subjects having no postural BP measurements. This may potentially lead to bias because patients who are having higher risks or symptomatic might be more likely having postural BP measured and thus the prevalence in our cohort might be overestimation.”
6.2. Address variables that showed no significant differences between groups and provide potential explanations.
A 6.2. Thank you for your advice. We have added a paragraph to explain this.
→ Page 6, Line 228-236: “Beta-blockers and alpha-blockers are thought to be more likely to precipitate OH than other classes of antihypertensives. However, in our analysis, none of the drugs were found to be particularly more likely to cause OH. Similarly, age and the prevalence of co-morbidities, such as diabetes and heart disease, which are known risk factors, were not significantly different in the OH group. The relatively younger population and fewer co-morbidities compared with previous studies might explain this difference. There are likely complex interactions between these risk factors and the development of OH. The small sample size and the retrospective nature of our study might limit the ability to detect the interplay of risk factors.”
7. Informed Consent Statement: Verify whether the Institutional Review Board supports the statement: “Patient consent was waived by the IRB due to the minimal risk of collecting non-sensitive data.” Emphasize that consent waivers are more about safeguarding personal information than minimizing risk.
A 7. Yes. The Institutional Review Board (IRB) endorsed the statement to minimize the risk of potential loss of confidentiality. Additionally, the IRB supported our team’s plan to safeguard personal information in accordance with the Personal Data Protection Act (PDPA) of Singapore. We have revised the statement accordingly.
→ Page 7, Line 279-281: “A waiver of consent was granted by the Institutional Review Board (National Healthcare Group Domain-Specific Review Board of Singapore, reference number 2023/00489) due to the minimal risk of collecting non-sensitive data and the measures in place to safeguard patient privacy.”
8. References: Update older references with more recent ones to reflect the latest research in the field.
A 8. Thank you for your advice. We have updated reference [2] and [5] accordingly.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe article focuses on the incidence and outcomes of orthostatic hypotension (OH) during hospitalization among patients with hemorrhagic stroke, marking the first study exclusively dedicated to this patient group. The background is clearly outlined, highlighting the prevalence and potential serious consequences of OH in hospitalized patients. Despite indicating a high incidence of OH during hospitalization for hemorrhagic stroke patients, no impact was observed on the length of hospital stay or discharge functional outcomes (measured by mRS scores). This could imply that current clinical interventions are effective; alternatively, it might be due to the limited sample size or other unidentified factors. While the paper mentions the association between OH and surgical intervention, it does not provide an in-depth explanation for why patients who have undergone surgery are more prone to developing OH, lacking a detailed exploration of the underlying mechanisms.
Author Response
While the paper mentions the association between OH and surgical intervention, it does not provide an in-depth explanation for why patients who have undergone surgery are more prone to developing OH, lacking a detailed exploration of the underlying mechanisms.
Reply: Thank you very much for your generous comment. We have explained briefly the proposed mechanism.
→ Page 7, Line 212-214: “Patients who require surgical interventions for
haemorrhage are often immobilized for longer periods, which could contribute to a
higher prevalence of OH in this group. Although we could not find any reports
specifically on the prevalence of OH in patients who required surgery for
haemorrhagic stroke, reduced heart rate variability and OH have been reported after
other types of surgeries, potentially related to opioid use and postoperative
inflammatory responses.”
However, as this is a brief report article, and the retrospective nature of the study, we highlighted the need for future studies to address the mechanism of such phenomena (Page 7, Line 269-270).
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsI commend the authors for their efforts in improving the quality of the study. All my suggestions were incorporated and thoroughly documented
