PONE-D-20-18075

Prevalence and Correlates of Metabolic Syndrome and its Components in Adults with Psychotic Disorders in Eldoret, Kenya

PLOS ONE

Dear Dr. Kwobah,

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 Oct 23 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,

Alberto Milan

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please provide additional details regarding participant consent. In the Methods section, please ensure that you have specified (a) whether consent was informed and (b) what type you obtained (for instance, written or verbal). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information

3. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

4. Please ensure that you refer to Figure 1 in your text as, if accepted, production will need this reference to link the reader to the figure.

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

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

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

**********

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

**********

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 analyses the correlation of metabolic syndrome and psychotic disorders in adults with a diagnosis of schizophrenia, schizoaffective disorder or bipolar mood disorder, compared to healthy individuals in the Moi Teaching and Referral Hospital in Eldoret, Kenya.

It is an interesting paper which focuses on a low resource context, which is often overlooked. It shows a significant increase of certain metabolic syndrome parameters in patients vs. controls, such as HDL levels, waist circumference and TG.

It is an observational study with definite limitations, that are underlined in the article itself: HbA1c was not measured, and most patients were on the same antipsychotic drug olanzapine. Moreover, most patients and controls were relatively young (mean age 33 vs. 35), which generally lowers the rate of CV events and metabolic syndrome. The controls, however, appear to have been chosen randomly in an appropriate manner. The authors reviewed a number of sociodemographic and laboratory variables.

I think this article has dignity to be published by itself. It is also a good starting point for possible future studies, possibly with a greater number of subjects and a more varied medication history and additional information, such as HbA1c value, arterial wall stiffness studies, long-term follow-up of patients and controls.

Reviewer #2: This is a cross-sectional study of metabolic health in 300 patients with psychosis from a hospital setting in Western Kenya. In a low-resource environment, the study authors found that patients with psychosis were more likely to have metabolic dysregulation (higher fasting glucose, BMI, lipid levels, waist circumference). They also identified relevant factors (older age, male gender, married status) associated with metabolic syndrome. This study presents important clinical findings from a region that has been understudied in the literature.

1. Methods (Page 5)– please clarify whether the inclusion criteria for the study required psychotic symptoms (for example, bipolar disorder with psychotic features)

2. Methods (Page 6) – please add details on whether the blood glucose levels were fasting

3. Methods (Page 6) – Please add details on which definition/criteria for Metabolic Syndrome was used for this study.

4. Methods (Page 6) – Please clarify how non-normally distributed variables were handled.

5. Methods (Page 6) – Please clarify if there was adjustment for multiple comparisons.

6. Discussion (Page 12) – While it may not be possible to fully explain why this study finding differed from other work in South Africa and Uganda, please expand upon whether the age, sex, antipsychotic treatments were similar to this study sample. A deeper examination of the differences in this population from South Africa (the source of most African studies on this subject) would establish why these studies should not be lumped together.

7. Discussion (Page 12) – Please clarify in the third paragraph discussing the obesity rates whether the comparison is with general population samples or with participants with psychotic disorders. Also, the varying rates across country are not fully explored – please add further discussion

8. Discussion (Page 12-13)– given the higher rates of obesity among women, it would be helpful to clarify if women and men had differences in demographic, medication, or other clinical factors that might be related.

9. Discussion (Page 14, 2nd paragraph) – please correct the typos in the second sentence “a 2.4% diabetes.”)

10. Discussion (Page 15) – the high rates of olanzapine usage are an important contributor to the metabolic health of these patients. Please clarify if the other African studies of metabolic health had similarly high rates of olanzapine or other SGAs with high metabolic risk.

11. Discussion (Page 15) – another key point for clarification in whether olanzapine does/does not contribute to metabolic health is whether there were demographic differences in those who were on olanzapine vs. another antipsychotic (age, sex, education level, age of onset) as these factors may confound this relationship.

12. Discussion – Please expand on the screening practices and treatment gaps within this particular treatment setting. Rates of monitoring of metabolic health for patients on olanzapine vary by treatment setting/provider – it would be helpful to not whether this is a common practice in this setting.

13. Discussion – Deinstitutionalization in Western countries impacted mental and physical health outcomes for patients with psychotic disorders. It would be interesting to discuss whether such practices have occurred in Kenya and whether that may influence the health outcomes in this population.

**********

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

[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-20-18075R1

Prevalence and Correlates of Metabolic Syndrome and its Components in Adults with Psychotic Disorders in Eldoret, Kenya

PLOS ONE

Dear Dr. Kwobah,

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 Jan 04 2021 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,

Alberto Milan

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

The paper has clearly improved, there are still several points to be reviewed by the authors

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

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: 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 #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #2: Yes

Reviewer #3: 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 #2: Yes

Reviewer #3: 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 #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: This is a study of metabolic syndrome among patients with psychosis and a non-psychiatric comparison group in Eldoret, Kenya. The study addresses an important problem in psychiatric treatment – the high rates of cardiometabolic disease and subsequent mortality among patients with psychosis. This is also one of the first studies from Kenya, as most studies are from South Africa, and showcase important clinical differences in low- and middle-income countries. The sample size is large (600 total), assessments and methodology are solid, and the discussion covers a number of relevant points regarding treatment gaps. The authors were able to put the study in context of other studies from Africa. I appreciate the author’s comprehensive response to our suggestions

1. Abstract – Results section: Please clarify that the marital status variable was widowed/separated/divorced (compared to never married and married groups). These were groupings show in Table 1.

2. Results – please note the age range of the participants in this study, to help clarify the relationship between older age and metabolic syndrome.

3. Results – please clarify whether the obesity findings in Table 4 were based on BMI or abdominal obesity. The BMI/abdominal obesity findings in the discussion should be mentioned in the results section as well.

4. Discussion – the finding that female gender was associated with decreased odds of metabolic syndrome but increased odds of obesity are puzzling and warrant further discussion.

5. Discussion- the discrepancy in gender findings on metabolic syndrome from the current study and South African study are also puzzling. Were there age/other demographic factor differences between the two cohorts? What were the findings regarding obesity in the two groups?

6. Discussion – additional interpretation/synthesis would be helpful to understand why the present study would differ from the Western Kenya study. Are the two groups of participants comparable in terms of demographic features or treatments?

7. Discussion – the low numbers of participants on agents other than olanzapine make it difficult to truly link olanzapine use to metabolic problems. It may be helpful to emphasize the finding that dosage of olanzapine was not linked to metabolic syndrome or other cardiometabolic abnormalities.

8. Discussion – please clarify what is indicated by “human resources for mental healthcare” – would those be increasing the staffing of mental health clinics or other types of support?

Reviewer #3: This article analyses the correlation of metabolic syndrome and psychotic disorders in adults with a diagnosis of schizophrenia, schizoaffective disorder or bipolar mood disorder, compared to healthy individuals iin Kenya.

This paper which focuses on a low resource context, which is often overlooked. It shows a significant increase of certain metabolic syndrome parameters in patients vs. controls, such as HDL levels, waist circumference and TG.

It is an observational study with definite limitations, however it seems reasonable and well written

**********

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.

Prevalence and Correlates of Metabolic Syndrome and its Components in Adults with Psychotic Disorders in Eldoret, Kenya

PONE-D-20-18075R2

Dear Dr. Kwobah,

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,

Alberto Milan

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 #2: All comments have been addressed

Reviewer #3: 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 #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #2: Yes

Reviewer #3: 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 #2: Yes

Reviewer #3: 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 #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: This is a study of metabolic syndrome among patients with psychosis and a non-psychiatric comparison group in Eldoret, Kenya. The study addresses an important problem in psychiatric treatment – the high rates of cardiometabolic disease and subsequent mortality among patients with psychosis. This is also one of the first studies from Kenya, as most studies are from South Africa, and showcase important clinical differences in low- and middle-income countries. The sample size is large (600 total), assessments and methodology are solid, and the discussion covers a number of relevant points regarding treatment gaps. The authors were able to put the study in context of other studies from Africa. I appreciate the author’s comprehensive response to our suggestions and believe the resultant manuscript is a clear and meaningful contribution to the literature.

Reviewer #3: no further comments the authors addressed all the comments raised; no further comments as previous one

**********

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