PONE-D-20-13239

The rising complexity of Multimorbidity in a middle income country

PLOS ONE

Dear Dr. Fernando,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Sep 06 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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We look forward to receiving your revised manuscript.

Kind regards,

Alana T Brennan

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: Partly

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: Yes

Reviewer #2: Yes

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4. 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 #1: No

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 article describes multi-morbidity in Sri Lanka based on data from a primary care center and a tertiary hospital. The article aims at adding to the literature by revising the characteristics of multi-NCD morbidity in Sri Lanka. The authors also look at the predictors of mental health in the selected population. The manuscript could be improved as suggested below.

MAJOR ISSUES

Overall.

1. Needs language revision – needs significant improvement on English

2. Not a clear research question/hypothesis. For instance, the stated goal is to describe multi morbidity however data is presented on association between multi-morbidity and mental health outcomes. It is not clear if mental health conditions is the outcome variable, if so, the hypothesis should be clearly stated.

Introduction

o The goal of the study is not clear. Is the goal to describe the characteristics of people diagnosed with NCD (i.e., age and sex [gender]?) or to describe the characteristics of people diagnosed with 2 or more NCDs?

Methods

Sample size: Description of sample size estimation is not clear

o If the study is descriptive in nature, what is the significance level for? Is this an analytical or descriptive study?

� Needs to provide rationale for not including all patients in the registry and limiting it to a sample size calculation.

� Were the people excluded different than those that remained in the study?

MINOR ISSUES

Overall

•

• Data was collected only for individuals over 20 years of age but no rationale is provided for this selection.

Abstract.

• Conclusions not supported by data

• Abstract needs to be rewritten

• Reorder the introduction

• Not clear why only regression for mental health.

Figures and tables.

• Figure 3 is not high resolution and not clear

• No need for tables under figures 1 and 2

Introduction

o Might need some reformatting of paragraphs

• Methods

o Selection of clinic/hospital needs to be better justified (is it representative of the population, why? If not, how to avoid bias)

o Again, provide rationale for selecting only individuals over 20 years.

o Needs to add rationale behind selecting diagnosis for inclusion.

o Formatting of age groups is different (line 109)

o Provide rationale for age groups

Methods. A. Sample Size

o Is the data extraction form provided?

Data analysis

� Why restricting to age 18 and older when the eligibility states age 20 and older?

o Suggest to use either SPSS or R. Indicate version, year, etc. full software citation.

• Results

o Not clear what is meant by “by the time they reach half the decade” – it would be best to describe the age group.

o The use of “increase” in line 148 suggests a baseline. I suggest to consider use another term that more accurately describes the comparision being made.

o Use n= XXX as opposed to XX/1600

o How does the proportion of multimorbidity relates to original size of age groups (an adjusted rate might be useful)?

• Discussion

o Could be more focused.

o Needs to better discuss the strengths and limitations of the study.

Reviewer #2: "The rising complexity of Multimorbidity in a middle income country " emphasizes important health issues. Below are some suggestions to strengthen the manuscript

Comments

1. Methods section: Please add subsections and reorganize as necessary to improve clarity and readability

2. Methods (line 109) please justify why these age categories were used, if possible referencing previous studies for compatibility

3. Methods (line 128) states the analysis was restricted " to those aged 18 years and older", however line 101 states "patients over 20 years ...". Please correct or clarify.

4. Table 2 Please clarify in the footnote which covariates were uncluded in the adjusted OR model. Would it be possible to present unadjusted and adjusted. Could additional factors be included in the adjusted model?

5. It is clear ethical approval was obtained from the relevant institute. Patient data was anonymous. Did patients give permission to the institute to use their data?

6. Please carefully check English language usage throughout the text.

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6. 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 #1: No

Reviewer #2: No

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-20-13239R1

The rising complexity of Multimorbidity in a middle income country

PLOS ONE

Dear Dr. Fernando,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR:

The reviewers and I both noted that you have done a nice job addressing the previous comments. There are some additional suggestions, in particular those raised by Reviewer 3, that would greatly strengthen the manuscript, if addressed. Please note, too, the suggestions for modifying the title and changing the language describing the mental health findings to better reflect the work you have done.

==============================

Please submit your revised manuscript by Nov 22 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Andrea Gruneir

Academic Editor

PLOS ONE

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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 #2: (No Response)

Reviewer #3: (No Response)

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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 #2: Yes

Reviewer #3: Partly

**********

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

Reviewer #2: Yes

Reviewer #3: I Don't Know

**********

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 #2: Yes

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 #2: Yes

Reviewer #3: Yes

**********

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 #2: Thank you for addressing almost all comments. Please additionally add subsection headers within the methods section

Reviewer #3: Examples of literature on MM in Intro and Discussion are largely from high income countries - when there are a reasonable number of publications from lower income countries that might be more appropriate.

Table 1 is useful, but could be more useful to have info by age and sex, plus a similar table of most common multimorbidities. Would want table of patient sociodemographic characteristics. The authors could please specify which variables were included in the adjusted regression analyses?

More details about the regression analyses are needed - describing the stepped process by which you did both sets of regression analyses - and especially the analysis including mental health variables.

And the conclusions about mental health need to be tempered - this is a cross-sectional study "...as the number of disorders increases, the risk of developing any mental disorders increases..."

The term "elderly" is considered pejorative, please instead use older persons, older adult, older population.

One of the biggest findings here is the high prevalence in 'young" age groups. This could be part of another analysis - (narrower age groups (20-29, 30-39, etc) and look at age of diagnosis - but for this publication, authors could emphasize this interesting finding about high MM prevalence in young age groups.

Finally, the title is misleading - it describes the burden of multimorbidity in a sample of patients, not its complexities.

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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 #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-20-13239R2

The rising complexity and burden of multimorbidity in a middle-income country

PLOS ONE

Dear Dr. Fernando,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR:

Thank you for taking the time to revise and resubmit your manuscript. I think that you have done a nice job of addressing the Reviewers' comments throughout the text. I would just like to see some modifications to the tables so that they are easier to read. In all tables, it would be helpful to have the sample size shown within the column headers so that the denominator for each cell is clear. For Table 2, you should consider having a total column (where you can show the prevalence of each condition for the full sample) and then the prevalence stratified by each sex and age; you sort of have this but you need the denominator for each column and perhaps a bit more cleaning up. You may want to consider similar adjustments to Table 3. There is a fair bit of data in your study and anything you can do to help your readers understand it would be useful.

==============================

Please submit your revised manuscript by Dec 28 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Andrea Gruneir

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

The rising complexity and burden of multimorbidity in a middle-income country

PONE-D-20-13239R3

Dear Dr. Fernando,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Andrea Gruneir

Academic Editor

PLOS ONE

Additional Editor Comments (optional): Thank you for your patience and for continuing to make revisions to this manuscript. I think that there are still some modifications to your tables that are required to make them as readable as possible, but also that there is no reason to hold back your manuscript at this point. Congratulations on this work!

Reviewers' comments: