Title: Dengue Score: a proposed diagnostic predictor of pleural effusion and/or ascites in adult with dengue infection

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1 Reviewer s report Title: Dengue Score: a proposed diagnostic predictor of pleural effusion and/or ascites in adult with dengue infection Version: 0 Date: 11 Feb 2016 Reviewer: Anthony Jin Shun Chua Reviewer's report: 1. Title: "adult" should be in plural. 2. Lines 28, 87, 207, 230 and 272: Remove "a/the diagnosis of". The phrase is somewhat redundant. 3. Line 40: Remove "degree of". It is understood that the authors were talking about the extent of hemoconcentration. 4. Line 46: Replace "This diagnostic predicting model" with "This prediction model". 5. Lines 46-47: The authors may wish to elaborate on why they feel that the prediction model is "suitable for calibration and good discrimination". 6. Lines 121 and 124: Remove "as a percent". 7. Lines : Replace "subtracting the peak albumin recorded with the minimum level, the dividing that value by the" with "subtracting the minimum albumin recorded, divided by the". 8. Lines : The authors should state the mathematical formulae for degrees of hemoconcentration and hypoalbuminemia, and AST and ALT ratios. It is very difficult for the readers to construct these equations by reading the authors' word descriptions.

2 9. Lines : It is very commendable that the authors stated how their sample size was derived at the beginning of their study. 10. Line 150: The authors should include references as they claimed that the conversion into a simplified risk score system was according to published methodologies. 11. Line 158: Replace "median age of 22 (11) years old" with "median age of 22 (interquartile range = 11) years old". It is not evident that the numeral in brackets was referring to the interquartile range. 12. Lines : This sentence is relatively confusing. If albumin concentration was only measured once, how did the authors obtained the "lowest" albumin concentration at critical phase? The authors may also wish to further elaborate on how is using lowest albumin concentration practical. 13. Lines : (i) Usually two continuous variables are being analyzed in bivariate analyses. It is unclear what the 5 variables in Table 3 were being analyzed against. (ii) Why is the ALT ratio not subjected to multivariate analysis when its p-value is significant (0.004 <0.05)? 14. Lines : It is unclear which two independent variables that the authors were referring to, have no interaction. 15. Line 181: It is unclear what the authors meant by "dividing the coefficient/standard error (2.38)". 16. Lines : The authors may wish to elaborate on how the correct prediction rate of 77.38% for pleural effusion and/or ascites was derived.

3 17. Lines : Replace the phrase "as a diagnostic predictor of" with "to predict". 18. Lines : This sentence is somewhat confusing. The authors are discussing about extents of hemoconcentration in patients without hemoconcentration? The authors may wish to rephrase the sentence. 19. Line 218: Replace "use of the best lower cut off" with "use of a lower cut off". 20. Line 219: Replace "missing dengue infected" with "under-diagnosing". 21. Line 220: Delete "contracting". 22. Line 222: Remove the "greater than or equals to" sign in "decreased". 23. Line 231: Insert ", respectively" after "two parameters". 24. Lines : Replace the two sentences with "We suggest using degree of hypoalbuminemia as a percentage to detect plasma leakage, similar to the concept of degree of hemoconcentration. However, due to the similarity in AROC between the 2 parameters, we selected the lowest albumin concentration at critical phase, which is more practical in daily practice, as albumin is only measured once.". 25. Line 236: Remove "to the third space". 26. Lines : Replace "DHF; therefore, it is biologically plausible to explain the association of the two conditions" with "DHF, thereby explaining the association between the two conditions".

4 27. Line 242: Replace "is the mechanism of" with "possibly contribute to". 28. Line 243: Replace "and" with "which in turn". 29. Line 246: Replace "we found the best AROC of the lowest platelet count" with "it gave the best AROC among all the variables tested". 30. Lines : Replace with "Liver cells are one of the targets of dengue viruses.". 31. Lines : This sentence contradicts what was mentioned earlier - that ALT ratio was not used in multivariate analysis. It was also shown in Table 3 that multivariate analysis was not performed for ALT ratio (as represented by "NA"). 32. Lines : The authors may wish to elaborate more on the "problem of the difference in reference limits of the AST between laboratories", and provide relevant references. 33. Line 274: Delete "high-". 34. Line 407: Delete "sum of". 35. Table 3: The constant in the multivariate logistic regression was not discussed by the authors throughout the manuscript. Overall: The language is generally good except for some mistakes in grammar and prepositions. Proof-reading by a native English speaker is recommended.

5 Are the methods appropriate and well described? If not, please specify what is required in your comments to the authors. Yes Does the work include the necessary controls? If not, please specify which controls are required in your comments to the authors. Yes Are the conclusions drawn adequately supported by the data shown? If not, please explain in your comments to the authors. Yes Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review? If an additional statistical review is recommended, please specify what aspects require further assessment in your comments to the editors. I am able to assess the statistics Quality of written English Please indicate the quality of language in the manuscript: Needs some language corrections before being published Declaration of competing interests Please complete a declaration of competing interests, considering the following questions: 1. Have you in the past five years received reimbursements, fees, funding, or salary from an organisation that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? 2. Do you hold any stocks or shares in an organisation that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? 3. Do you hold or are you currently applying for any patents relating to the content of the manuscript? 4. Have you received reimbursements, fees, funding, or salary from an organization that holds or has applied for patents relating to the content of the manuscript? 5. Do you have any other financial competing interests? 6. Do you have any non-financial competing interests in relation to this paper?

6 If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If your reply is yes to any, please give details below. I declare that I have no competing interests. I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license ( I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published. I agree to the open peer review policy of the journal

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