Predictors of recovery rate among undernourished HIV-positive adults treated with ready-to-use therapeutic food at Debre Markos Comprehensive Specialized Hospital: A retrospective cohort study

Habtamu Gebremeskel Woldie; Daniel Bekele Ketema; Mulatu Ayana; Animut Alebel

doi:10.1371/journal.pone.0255465

Peer Review History

Original SubmissionFebruary 20, 2021
30 May 2021 Decision Letter - Obinna Ikechukwu Ekwunife, Editor PONE-D-21-05739 Predictors of recovery among undernourished HIV-positive adults treated with ready-to-use therapeutic food at Debre Markos Comprehensive Specialized Hospital: a retrospective cohort study PLOS ONE Dear Dr. Daniel Bekele Ketema, 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. ============================== Kindly ensure that you make all the data underlying the findings in the manuscript fully available. 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Kind regards, Obinna Ikechukwu Ekwunife, PhD Academic Editor PLOS ONE Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. 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. In ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records used in your retrospective study. Specifically, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information.' [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: No Reviewer #2: No ****** 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: Yes ****** 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: Manuscript PONE-D-21-05739. The article on "Predictors of recovery among malnourished adults with HIV treated with ready-to-use therapeutic foods" is interesting as it addresses nutritional support, which is increasingly recognized as an important part of the care package for people living with HIV/AIDS. The aim of this research is therefore to estimate the recovery rate and predictors among malnourished adults with HIV/AIDS treated with therapeutic foods. To improve its work, it is suggested to. 1. In the Abstract, include a paragraph of the contribution of this research and future work. 2. Review the English grammar and spelling of the entire paper. 3. Indicate whether this research uses publicly available information or has a data set with access to the data for researchers to replicate the experiment. 4. To make your research replicable I suggest placing the data from the study with public access; you can create one at https://data.mendeley.com/ 5. Improve the quality and resolution of the figures. 6. In the Conclusions section include a paragraph about future work to be done. Reviewer #2: Abstract � Line 41, “clinical stage” should be specific. So it should be modified as “ WHO clinical stage” � Line 44-45, this study found that the overall nutritional recovery rate was below the World Health Organization recommended standard. Please state the recommended standard rate. Introduction � Why you mentioned the specific category of some variables (WHO stage I and II, absence of opportunistic infection, CD4 cells percentage above the threshold)? � The introduction should show the gap of previous studies Methods � Line 114-117, “Currently, a total of 9,612 people living with HIV had ART follow up at Debre Markos referral hospital. Of whom, about 3,702 people had active ART follow up among these 3,375 were adults”. It is not clear. What is the difference between “Current ART follow up=9,612” and “active ART follow up=3702”? � The eligibility criteria should be stated separately and clearly � Did you include patients with edema (might affect the measurement accuracy of outcome variable) � During sample size calculation, what was the ratio of unexposed to exposed group in each variables? You should state clearly � Line 170-171, I hope the follow up period for MAM and SAM patients are completely different. If so, how can diagnose default or censored with the same follow up period? � Who were classified as “defaulted”? Are they similar to participant who didn’t experience the event at the end of the study? � Line 180-181, the data source is not clear. Did you collect the data only from patients chart? Is there any other sources? To avoid information bias, it is advised to use different data sources. � Line 208: Adjusted hazard Ratio (aHR) wand 95% CI………..” change the word “ wand” to “ with” Result and discussion � Line 280-282, participants were classified as mild, moderate and severe based on their BMI which was also your outcome variable. So, a patient with high BMI (near to discharge criteria) at baseline is expected to gain the target BMI faster than a patient with extremely low BMI. No need of research. It was better to do stratified analysis (mild, moderate or severe) � In table 6, why did you take the risk groups (rural, WHO clinical stage III or IV, Unemployed….) as a reference category? I hope your research problem is long recovery time and all the above categories are risk for your problems. � Line 360, “number of household” is not clear. ****** 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. https://doi.org/10.1371/journal.pone.0255465.r001
Revision 1
10 Jun 2021 Author Response First: We really appreciate the editor and reviewers, and we would like to express our thanks for devoting their time and look at each and every word of the article. Review Comments to the Author Reviewer #1: Manuscript PONE-D-21-05739. The article on "Predictors of recovery among malnourished adults with HIV treated with ready-to-use therapeutic foods" is interesting as it addresses nutritional support, which is increasingly recognized as an important part of the care package for people living with HIV/AIDS. The aim of this research is therefore to estimate the recovery rate and predictors among malnourished adults with HIV/AIDS treated with therapeutic foods. To improve its work, it is suggested to. 1. In the Abstract, include a paragraph of the contribution of this research and future work. Response: Thank you for suggestion. As per your suggestion we have included the significance of this study for concerned body and future researcher (Check Abstract section line # 26-30, page 2) 2. Review the English grammar and spelling of the entire paper. Response: Thanks for your comments: We extensively reviewed the manuscript for grammar and spelling error (Check the clean manuscript) 3. Indicate whether this research uses publicly available information or has a data set with access to the data for researchers to replicate the experiment. Response: We provide a Data Availability Statement (“All relevant data are within the manuscript and its Supporting Information files”) on the PLOS ONE submission system 4. To make your research replicable I suggest placing the data from the study with public access; you can create one at https://data.mendeley.com/ Response: thank you for your recommendation: We prefer to set all relevant data within the manuscript and its Supporting Information. Therefore, we submit the data set as a supporting file with a data set name: Dataset_Recovery. 5. Improve the quality and resolution of the figures. Response: As per your direction we improved the quality and resolution of the figures (Check Fig 1, Fig 2, and Fig 3) 6. In the Conclusions section include a paragraph about future work to be done Response: Thank you; We include what should be done in the future (Check Conclusion section line# 369-371 page21) Reviewer #2: Abstract � Line 41, “clinical stage” should be specific. So it should be modified as “WHO clinical stage” Response: thank you for your suggestion: We have corrected it as per your suggestion (Check Abstract section line#49, page 3) � Line 44-45, this study found that the overall nutritional recovery rate was below the World Health Organization recommended standard. Please state the recommended standard rate. Introduction Response: We have stated the recommended WHO standard (Check Abstract section, Line#48) � Why you mentioned the specific category of some variables (WHO stage I and II, absence of opportunistic infection, CD4 cells percentage above the threshold)? Response: we mentioned specific categories of variables. This is recommending to highlight advantages and dis advantageous groups in terms of outcome of interest. This intern helps for researcher, policy makers and programmer to set a priority and plan for intervention. � The introduction should show the gap of previous studies Response: We have indicated identified gaps of existing literatures and highlighted how this research fill that gaps (check Introduction section, Line# 88-91, Page 5) Methods � Line 114-117, “Currently, a total of 9,612 people living with HIV had ART follow up at Debre Markos referral hospital. Of whom, about 3,702 people had active ART follow up among these 3,375 were adults”. It is not clear. What is the difference between “Current ART follow up=9,612” and “active ART follow up=3702”? Response: Thank you for insightful comments. The idea of the statement is to highlight background information about total number of patients enrolled on ART since started and till now. Therefore, we revised this statement to avoid such confusions for the readers (Check Method section, Line #113-117, page 6). � The eligibility criteria should be stated separately and clearly Response: Check (Method section, Line # 124-128, page 6-7) � Did you include patients with edema (might affect the measurement accuracy of outcome variable)? Response: Thank you for your comments, we have already excluded patients presented with edema (Check Method section, Line #127-128, Page 7) � During sample size calculation, what was the ratio of unexposed to exposed group in each variable? You should state clearly Response: thank you for this comment. Ratio of unexposed to exposed depends upon the outcome of interest and study population. In our case the ration of exposed to un exposed for the study population is 1 to 1 (Check Method section, Line # 140-141, page 7) � Line 170-171, I hope the follow up period for MAM and SAM patients are completely different. If so, how can diagnose default or censored with the same follow up period? Response: Regardless of their bassline nutritional status either MAM or SAM, participants who were not fully contributed for outcome variable were considered as censored. The follow up period could not have expected to be similar for MAM and SAM patients. For this study patients were considered us censored when the end point of the interest (Recovery) has not been observed due to certain reason like � Patients still on treatment (on RUTF) but un recovered at the end of the study � The recovery status of patients at the time of analysis might not be known because of o Default (lost follow-up) o Death � Who were classified as “defaulted”? Are they similar to participant who didn’t experience the event at the end of the study? Response: In this study patients were classified as defaulted when they did not reach a BMI of 18.5 and dropped out of the program before the end of three (MAM) or six (SAM) months follow up (Check Method section, Line # 174-175, page 9). There is an important assumption made in survival analysis to make appropriate use of the censored data. This is called non-informative censoring and essentially assumes that the participants whose data are censored (defaulted) would have the same distribution of recovery time if they were actually observed. Therefore, those who are defaulters have similar event distribution with patients whose outcome is observed. � Line 180-181, the data source is not clear. Did you collect the data only from patient’s chart? Are there any other sources? To avoid information bias, it is advised to use different data sources. Response: Thank you for your comment: In addition to patients chart we have used patient’s registration book as source of data for this study (Check method section, line # 184-185, page 10) � Line 208: Adjusted hazard Ratio (aHR) wand 95% CI………..” change the word “ wand” to “ with” Response: we have addressed this typographical error (Check method section, line # 213, page 11) Result: Result and discussion � Line 280-282, participants were classified as mild, moderate and severe based on their BMI which was also your outcome variable. So, a patient with high BMI (near to discharge criteria) at baseline is expected to gain the target BMI faster than a patient with extremely low BMI. No need of research. It was better to do stratified analysis (mild, moderate or severe) Response: Thank you for this comments which allow us to elaborate more The baseline nutritional status (mild, moderate and severe) is not our outcome variable rather used for adjusting RUTF dose and follow up time. Our outcome variable is time to recovery after initiating this therapeutic feeding. The conclusion you made “a patient with high BMI (near to discharge criteria) at baseline is expected to gain the target BMI faster than a patient with extremely low BMI” might be true. This information is supported by many existing literatures. But it did not mean no need of conduct research in this area. In the scientific world, we can support the existing evidence with available data on hand to facilitated evidence based decision by providing information from different segments. That means exploring this fact at particular study site is important. In addition, quantifying this fact after adjusting with different potential confounders which were not addressed before may produce parsimonious estimate for population parameter. Moreover, this known fact by itself will be used for adjusting other potential predictor variables. � In table 6, why did you take the risk groups (rural, WHO clinical stage III or IV, Unemployed….) as a reference category? I hope your research problem is long recovery time and all the above categories are risk for your problems. Response: thank you for this important comments. It’s best to choose a category as a reference that makes interpretation of results easier. As you stated above long recovery time is a problem for our study; and selecting non exposed group as a reference give a sense with easy interpretation. However, it is possible to interpreting our results in terms of accelerated time. That means those patients who were in the non-exposed group have accelerated recovery time compared to those who are exposed. Moreover, we choose these categories as a reference is for comparison purpose with other similar studies. Note: If our justifications were not convincing we are ready to accept your suggestion � Line 360, “number of household” is not clear. Thank you: we have corrected it as “Number of persons in the household” (Check discussion section, line # 359-360, page 21) Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0255465.r002
19 Jul 2021 Decision Letter - Obinna Ikechukwu Ekwunife, Editor Predictors of recovery rate among undernourished HIV-positive adults treated with ready-to-use therapeutic food at Debre Markos Comprehensive Specialized Hospital: a retrospective cohort study PONE-D-21-05739R1 Dear Dr. Daniel Bekele Ketema, 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, Obinna Ikechukwu Ekwunife, PhD 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 #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: The article has been significantly improved, the reviewers' suggestions have been implemented. I suggest it be considered for publication. ****** 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: No https://doi.org/10.1371/journal.pone.0255465.r003
Formally Accepted
23 Jul 2021 Acceptance Letter - Obinna Ikechukwu Ekwunife, Editor PONE-D-21-05739R1 Predictors of recovery rate among undernourished HIV-positive adults treated with ready-to-use therapeutic food at Debre Markos Comprehensive Specialized Hospital: a retrospective cohort study Dear Dr. Ketema: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Obinna Ikechukwu Ekwunife Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0255465.r004

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