PONE-D-23-25038Are young and older children with diarrhea presenting in the same way?PLOS ONE

Dear Dr. Das.

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Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is an understudied and important topic given most research on diarrhea has focused on the under-5 group in LMICs. This is a straightforward but well done dataset analysis of older children at two hospitals in bangladesh that helps provide an understanding of the presentation and epidemiology of this older group for those working in the region.

General comments:

- how was the 5-9 age group decided to be the focus of this study as presumably other age groups (particularly adolescents) were part of the datasets? Adolescents are another highly understudied group, and one might consider including these patients in analysis, or discuss whether there may be plans to include in a future study which would be greatly needed

- suggest that the authors revise the discussion for improved clarity and flow, to focus on how this study's results fits in with the prior literature and give recommendations on how the authors would like to see their results applied to improve patient care and public health policies. additionally what are the highest priority areas for research in this older child group that are needed?

- suggest plos one team assist with english grammar due to minor errors throughout - for instance

"5-9 years of children" should be rephrased to "children 5-9 years of age" etc

specific edits:

Line 55-7: please cite the mortality rates from diarrhea in older children globally as well as in bangladesh/asian region if these exist

Study population/study site:

- Please include more details on inclusion/exclusion criteria. Also how was diarrhea defined? Did this include acute/chronic diarrhea? What about other disease in which diarrhea was just one presenting symptom?

- Clarify how random selection for controls was performed, what were inclusion/exclusion criteria for the 0-5 year group?

- Please also give some more details about icddrb and the Dhaka and Matlab hospitals for readers who are unaware. what types of patients are served, differences between matlab/dhaka, cholera seasonality, etc.

- Do patients with the most critical illness get transferred? I note that it is later mentioned there were no deaths in this age group at either hospital - is this due to transfer for more severe cases to other facilities perhaps? Would give some context and data if available, or cite as a limitation if not available.

Statistical analysis

- how were the outcome variable and covariates selected from those available in the datasets? Please provide rationale and citations whenever possible

Line 151: what was suspected reason for demographic change during covid? How would this impact interpretation of your results?

Line 161: a the authors expand on their speculations why these variables (parental illiteracy, shorter duration, more dehydration, etc) were associated with the older child group? shorter duration perhaps to higher presence of cholera/less rotavirus? Or other explanation? Can add this in discussion. also how might these findings be used to improve care by clinicians who treat these patients?

Line 171: h/o should be spelled out

Line 216: spell out abbreviations such as CDS at first use

Discussion section:

- In general this section needs to be more focused and to emphasize the most interesting findings of THIS study. there is relatively little discussion of the actual findings from the current study. additionally there is quite a bit of discussion on general child mortality however this should be reframe to focus on diarrheal mortality and how this study findings fit into the existing literature.

- There is no comment on the findings of those variables associated with older groups - parental literacy, short duration of symptoms, cough, fever, convulsions, etc. these are interesting findings and would like the authors to expand on why these were associated in this patient population. Particularly how to frame the understanding of how parental literacy and diarrheal presentation in older children are associated in Bangladesh context.

Line 221-22 - need more details about this review, what it studied, the main findings. Details are lacking and hard to understand how this current study results fit with this

Reviewer #2: Comments

Major comments:

1) Your manuscript requires major revision of % writing

2) First of all, your outcome (dependent variable) should be “diarrhea” for your Table 1 and Table 2. Therefore, you have to re-construct Table 1 and Table 2 using ‘Diarrhea’ as outcome variable and all the variables listed in both tables as independent variables using bivariable logistic regression to calculate the unadjusted odds ratio. Later on, those variables socring p-value < 0.25 to take them to the final model (Multivariable logistic regression).

3) Your Table 3 is incorrect. You have to construct another Table 3 which mainly focuses on multivariable logistic regression by taking those variables from Table 1 and Table 2 (after incorporating the comments given in the above 2nd major comments) which scored p-values less than or equal to 0.25. Mind you, you have to analyses both unadjusted odds ratio and adjusted odds ratio in Table 3 after including those variables with a score of p-value < 0.25. Therefore, all your Tables (Table 1, Table 2, and Table 3) are incorrect. With these incorrect analyses you cannot, discuss, you cannot conclude and you cannot recommend. Therefore, I will stop reviewing your manuscript now. This is because, all your results, discussions, conclusion and recommendations will definitely be changed after complying with the comments given above. Mind you, this is your major of major revisions. Therefore, I will review your second manuscript after incorporating all what has been commented above.

Minor comments:

1) Avoid unnecessary open space between title and authors name and between authors name and affiliation. Example, line number 2 and 5 have nothing to indicate

2) Your Table 4 may be correct, but I will see it after you incorporated all the major comments given above.

Sections

Page-2

Abstract

Rewrite your abstract using the structured way of abstract writing i.e. divide it into sub-sections Background, Method, Results, and Conclusion

L25: every single digit number should be written in word. Therefore, write <5 in word “less than five” and do the same correction throughout the document

L26: delete “children” and replace it by “diseases”

L26 – L27: the sentence “More young children are now surviving and improving the survival of older children” is meaningless. Re-write it meaningfully!!!

L33: Every time the word “respectively” should be preceded by comma. Therefore, add comma after the word “age”

L38: Don’t start a sentence with abbreviation; rather write in full form as “Vibrio cholerae”

Page-3

Introduction

L75 – L76: The justification “In recent decades, little is known about the burden of diarrheal disease in older children and adolescents” doesn’t go in line with your title. Therefore, modify it as “In recent decades, little is known about the burden of diarrheal disease in children under five and in older children five to nine years”

Page-4

L81: add ‘s’ to statement and make it “Statements”

L86: Don’t start a sentence with abbreviation ‘ERC’. Rather, write the full form ‘Ethical Review Committee’

Page-5

L93: Same comment as above, write the full form of DDSS

L104: the 11th reference should be placed between SPSS and the full stop

L108: Delete ‘0-<5’ and replace it by ‘under five’

Page-6

L110 – L111: Delete all the (%) from the two lines

Page-7

L133: Delete ‘simple’ and replace it by ‘bivariable’

L136: Delete ‘< 0-5 years’ and replace it by ‘less than five years’

L146: Delete colon from ‘Result:’

L147 – L148: the sentence “From 2012 to 2021, in Dhaka Hospital, out of a total of 28,781 surveillance patients, 5 to 9 years of children were 614 (%), randomly selected 2456 (%) children from 14,684 under -5 children (Figure 1).” is non-sense. Please re-write it meaningfully

L149 – L151: still the sentence “During the study period, in Matlab Hospital, out of 12,499 surveillance patients, 5 to 9 years children were 278 (%), and we randomly selected 1112 (%) children from 6,460 under-five children (Fig 1).” is non-sense. Re-write it meaningfully

Page-8

L160: Don’t start a sentence with number. Write it as “Five to nine years”

L164 – L 166: From Table 1 delete ‘Ref’ and replace it by ‘1’. This is because you are taking that option as a reference, so it will have an Odds Ratio of 1. Furthermore, italicize CI and p from p-value. Similarly, do the same correction throughout the manuscript.

In this Table 1 please enclose the CIs of the variables ‘The water treatment method used’ and ‘Toilet facility’. Moreover, where are the ORs with the CI for the variables ‘Presence of convulsion’ and ‘Outcome’?

From Table 2 for the variable ‘Maternal education’ you have to take the option ‘Literate’ as a reference; therefore, delete the OR with its CI and replace it by 1

Comments on References

Reference #3: It is too old data in 2008, it doesn’t describe the current situation. Therefore, remove it and replace it by the most recent one

Reference #4: It is too old data in 2008, it doesn’t describe the current situation. Therefore, remove it and replace it by the most recent one

Reference #9: Lacks page number. Therefore, include the page number after going back to the original article

I will continue evaluating the references in your second draft after addressing the major comments given above!!!

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Reviewer comments.docx

Are young and older children with diarrhea presenting in the same way?

PONE-D-23-25038R1

Dear Rina Das

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Sanjoy Kumer Dey, M.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: The authors have adequately addressed all the comments raised in a previous round of review. I am completely satisfied with their responses. I think, the manuscript is suitable to publish in this journal.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: Yes: Shuvra Kanti Dey

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