All reviews of published articles are made public. This includes manuscript files, peer review comments, author rebuttals and revised materials. Note: This was optional for articles submitted before 13 February 2023.
Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the article is rejected). If the article is accepted, then reviewers who provided their name will be associated with the article itself.
Thank you very much for your hard work and accepting the constructive criticism of the reviewers. You manuscript is much improved.
Thank you very much for working to move this manuscript toward publication. Please see the reviewers' remaining comments.
Thank you for the opportunity to review this revised manuscript. In terms of basic reporting, I found this to be much more readable, and believe that it clearly presents the material in professional scientific English. There are a few areas that still require copyediting, but this is quite minor. These are listed below.
1. Line 136: The phrases “in males” and “in females” should be outside the parentheses in this sentence.
2. Lines 174, 175: The word "triglyceride” in these lines should be revised to “triglyceride level.”
3. Line 230: Please remove the “is” after “findings” in this line.
4. Line 256: Consider adding a formal “limitations” subheading here.
After reviewing the revised manuscript and reviewer response, I feel that the experimental design is sufficient for the research question and have no further issues or questions.
I appreciate the time spent mitigating the strength of the conclusions to better match what a study of this nature can allow in terms of interpretation. There is, however, one area where such mitigation is still needed. Line 51 of the abstract suggests that the variables noted as significant within the study contribute to an "increased risk" of stroke. This, however, cannot be confirmed without prospective study. I would suggest revising this sentence to state that these variables have "prognostic value" with regard to stroke instead, as this is the interpretation given throughout the body of the article.
I appreciate your attention to the reviewer comments and feel that your article is nearing publishable form.
While a few minor issues exist that require further correction I do not believe that this will prove difficult and, once they are addressed, I anticipate acceptance of your work. Congratulations on a interesting study.
Please see the reviewer's suggestions and seriously consider them. In particular the comments from Reviewer 2 are very important and the submission will need to be thoroughly re-reviewed
The article seems to clearly address most areas implied by basic reporting. While some additional editing is needed for clarity in the English language, and a number of additional clarifications are needed, I think that these should be eminently addressable via revision. Please see my comments to the author below for a line-by-line analysis of the manuscript.
The experimental design appears to be adequate for the question. Certain elements require additional clarification, however, as listed below in in my line-by line commentary. Again, these should not be difficult to accommodate.
While the overall findings do seem valid, I did note a number of areas in the Results and Discussion, however, where the interpretation given to the data was confusing or questionable. As above, however, I do not believe this will be excessively difficult to address via appropriate revision. Please see my line-by-line critique below for specific details.
Thank you for the opportunity to review this study. This paper uses multivariate regression techniques to investigate key factors associated with recurrent stroke in Malaysia. While many of these factors have been explored in the western world, little data has yet been published in Malaysia, and this study thus represents an incremental, but important, increase in our knowledge regarding this area of care. On close review a number of issues were noted that will need to be addressed prior to acceptance, but many of these represent clarifications or enhanced explanations and should thus not be difficult to accommodate. I did not find any severe methodological flaws. To aid your team in making the needed corrections, I have structured my critique below according to the article's subheadings.
Overall:
1.Editing is needed for grammar and clarity.
Abstract:
1.Line 40: I am not certain what is meant by a "contradictory" relationship. Please clarify.
2.Line 58: While it is indeed possible, the association of triglyceride levels with stroke does not necessarily imply a causative relationship. Therefore, I think this conclusion needs to be mitigated somewhat.
Introduction:
1.Line 101: Please delete the word observational. The same content is implied by your use of the adjacent word exploratory.
2.Lines 107-115: Please clarify further how the event history analysis approach you describe here represents an improvement on more simple quantifications. What, specifically, do you expect this approach to yield in terms of greater insight about the relationship between the lab variables tested and stroke risk?
Methods:
1.Overall: The Introduction implies that event history analysis was used in this study and that this somehow offers more accurate findings. I did not see this technique mentioned or explained at all, however, in the Methods. Given its important to your study, please address how your team employed this technique more clearly.
2.Lines 144-145: It is unclear to me how a time to occurrence variable can be coded as yes/no. I would expect a scalar time interval to be used instead. Please clarify.
3.Line 148: By "censored" do you mean excluded? Please clarify your use of this word here and throughout the article.
4.Line 149-155: Please provide these numeric concentrations in mg/dl as well as in the current mmol/L notation. This will enable your results to be more readily interpretable to a wider swath of readers.
Results:
1.Line 173-174: The grammar of this sentence makes it unclear. Please rephrase.
2.Line 179: Please clarify what is meant by "25%" significant. What p-value would this correspond to? The more typical 0.05 p-value does not seem easily relatable to this number and if, in fact, p=0.25 was used at this phase, please state why.
3.Line 179-183: The sentence is unclear. When you say that you "considered" these, do you mean that you selected likely variables out of the 10 that were significant based on theoretical concerns? If so, what was the basis for this selection? Also, why distinguish within the Results between primary and confounding variables. At this point all that you can truly say is that a selection of variables were significant at the designated p-value. I believe this section should be revised to reflect this, and that the discussion of potential causes versus confounders more properly belongs in the Discussion.
4.Lines 193-204: This section is a little difficult to follow in terms of what is being presented, especially as concerns the findings of the multiple models. What I gathered from the statements here is that, for all comers, only total cholesterol had a significant association, but when DM is included as a variable, triglycerides becomes predictive as well. This is not clear, however, and appears to be contradicted by information within the Discussion. Please revise for clarity.
Discussion:
1.Lines 214-217: This is a much clearer statement of the findings of the multivariate regression. Please revise the Results accordingly.
2.Lines 218-219: This line suggests that impaired glucose metabolism does predict reoccurrence (albeit weakly), which seems to directly contradict the statement in line 215 that abnormal glucose level does not predict stroke risk. This may, however, be due to the specific way you are using the terms. Please clarify.
3.Line 233: I am confused as to your use of the term "confounding variable" here. A confounder is typically seen as something which induces unwanted variance that diminishes a study's predictive value. In this case, however, dyslipidemia seems to be a legitimate predictor, rather than a confounder. Accordingly, we ask that you consider your use of this term throughout the paper to make sure it conveys what you wish it to.
4.Line 237: The statement that dyslipidemia and total cholesterol confound seems oversimplified, as the presence of a dyslipidemia would naturally lead to a higher total cholesterol and thus they are in many ways measures of the same thing. While I appreciate the observation that Malaysian diagnostic bias may indeed render a dyslipidemia diagnosis a partial confounder, the above consideration likely also contributes to the picture. Overall, more clarity is needed as to how the term "confounder" is being used and why specific variables were classified in this way.
5.Lines 269-277: While I agree in principle that reducing total cholesterol medically may help with stroke, your actual results only show a degree of association, not a clear causative influence. For the sake of accuracy and clarity, please consider stating this more clearly either here or in the Limitations section.
In summary, this is a promising article that, while not entirely groundbreaking, will be beneficial to practitioners in Malaysia. While a number of edits are needed I do not believe they will be difficult to perform, and once these are made I think the article will merit publication. Thank you again for the opportunity to review your work. I look forward to reading the next iteration.
Completely unsuitable . poor English
Design is not adequate : No data is given about risk factors of first ever stroke. No data is given about current or previous therapy (anti hypertensive, anti diabetic etc.., statins etc..)
No information about mortality, about atrial fibrrillation and about other important risk factors (for instance anti coagulant therapy)
All text and materials provided via this peer-review history page are made available under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.