PONE-D-20-10789

Longitudinal association between mental health and future antibiotic prescriptions in healthy adults: Results from the LOHAS

PLOS ONE

Dear Dr. Yamamoto,

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.

The manuscript by Yamamoto et al. is well assessed by the two reviewers. However, there are still minor revisions in the present form. Read carefully the comments and respond to them appropriately.

Please submit your revised manuscript by Aug 10 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Masaki Mogi

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: Yes

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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?

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: 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: Thank you for giving me the opportunity to review this manuscript, which describes the association between mental health and prescription of antibiotics.

The authors found that individuals with poorer mental health were less likely to be prescribed antibiotics, compared to individuals with better mental health. I believe the manuscript is well written, I enjoyed reading it, and all the analysis and explanations are clearly described. I have a few comments that might help the authors improve this manuscript.

P5 L95: The authors call this design “retrospective” but data were collected prospectively, so I suggest to reword in order to not confuse the reader.

P5 L 113: It would be useful to describe properly the selection of the study population. How many people were invited to participate? How many declined? How many excluded because of antibiotics at baseline? Or because of comorbidity? A flowchart would be very useful.

P6 L122: The authors excluded participants who died or moved without any prescription. I believe this is methodologically wrong. In my opinion, the best option would be to include everyone and censor them at time of dead/emigration. Then the analysis could be performed with a Poisson model or a similar model that allows for different follow-up time in different individuals. Alternatively (if death or emigration is rare), one might exclude all those who emigrate or die (although this might bias the results). However, the authors used one approach for those with antibiotics, and another for those without. In any case, I think the same approach should be used for all study participants (this also refers to P9 L193).

P6 L133: The authors used the prescription database to identify antibiotics, but it is not clear where the disease (assumed to be treated by the antibiotics) was obtained from. Is this from another database? It would be interesting to see the concordance between the two data sources: how many are in both, how much time apart the two occurrences are, etc.

P9 L203: It would be useful to add a reference to Rubin’s rules for those unfamiliar with multiple imputation.

P15 L323: The results of this study are clear: those with poorer mental health are less likely to be prescribed antibiotics. Have the authors considered looking only at infections? Is it possible that the rate of infections is the same but not treatment not adequate for those with mental health problems?

P16 L338: “The absence of any significant association” should be rephrased. There is a significant association, in the other direction.

P17 L363: I think the discussion would benefit of some limitations related to the internal validity of the study. For example, is there any potential selection bias (the flow diagram mentioned above would help assess that)? Could there be some misclassification of mental health status or antibiotic use? What happens with the difference between antibiotics prescription and actually taken?

Finally, I have some general comments. Why did the authors decide to exclude individuals with comorbidities? Would not be possible to investigate those? Or adjust for comorbidities in the analyses? Also, what is the main idea behind excluding patients with antibiotics at baseline? I would understand this approach if causal conclusions had to be taken, for example which exposures to change to prevent future antibiotic use. However, in this study, the main aim is to describe whether individuals with poorer/better mental health are less/more likely to use antibiotics, could this question be answered with a cross-sectional design, in which establishing a temporal relation is not the main aim?

Reviewer #2: Please carefully revise the manuscript for English grammar. Otherwise I very much enjoyed reading this study, it is the first study to examine the association between mental health and antibiotic use in the community setting, a topic I have very often wondered about, thank you for your work, it should be a welcome addition to the literature.

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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.

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Reviewer #1: Yes: Oleguer Plana-Ripoll

Reviewer #2: Yes: Tony Velkov

[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.]

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PONE-D-20-10789R1

Longitudinal association between mental health and future antibiotic prescriptions in healthy adults: Results from the LOHAS

PLOS ONE

Dear Dr. Yamamoto,

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.

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

The authors well responded to the Reviewers' comments. However, minor revision is still necessary in the present form. Respond the comments appropriately.

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

Please submit your revised manuscript by Oct 05 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,

Masaki Mogi

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 #1: (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 #1: Yes

**********

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

Reviewer #1: Yes

**********

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 #1: Yes

**********

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 #1: 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 #1: Thank you for addressing all my comments.

Regarding the selection of the study population (and the included flowchart, sorry for having missed that in my first review), it would be useful to know how many were invited to participate. According to the manuscript, 984 consented to participate, but it is unknown how many declined, and this is important to assess potential selection bias. Please refer to Fig 1 also in the methods section when study population is described.

Thank you for adding text about the internal validity in the discussion. However, I think further explanations are required. I think the sentence “Selection bias might have occurred because not all residents participated” should he complemented a little bit. How many people agreed or not to participate (see my previous point)? If most people participated, then selection bias is unlikely. Do you think participation rates will be similar among those with/without antibiotic use? Or those with/without mental disorders? Selection is likely to cause bias only if associated with both exposure and outcome. Regarding information bias, do you think potential misclassification of the outcome will be differential (different among exposed and unexposed) or non-differential? If non-differential, the bias is likely to be towards the null. I think the manuscript will benefit from such thoughts in the discussion section.

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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 #1: Yes: Oleguer Plana-Ripoll

[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.

Longitudinal association between mental health and future antibiotic prescriptions in healthy adults: Results from the LOHAS

PONE-D-20-10789R2

Dear Dr. Yamamoto,

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.

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Kind regards,

Masaki Mogi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

No further comment.

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 #1: All comments have been addressed

**********

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 #1: Yes

**********

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

Reviewer #1: Yes

**********

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 #1: Yes

**********

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 #1: 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 #1: (No Response)

**********

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 #1: Yes: Oleguer Plana-Ripoll