https://orcid.org/0000-0003-2660-207X
Peer Review History
| Original SubmissionJune 17, 2020 |
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PONE-D-20-18648 Factors associated with unfavorable treatment outcomes in patients with rifampicin-resistant tuberculosis in Colombia PLOS ONE Dear Dr. Chaves Torres, 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. While the research is an excellent use of programmatic data and is in an important area in the field of TB, there are a number of areas in which it could be improved for re-review and further consideration of publication. Please can you systematically address the reviewers' comments paying special attention to: 1) Enhancing the literature review and introduction with relation to social determinants of TB and their further association with adverse TB treatment outcomes 2) Clarify some parts of the methods including: inclusion and exclusion criteria; evidence informing inclusion of independent variables into your regression model (e.g. method of diagnosis); and methods used to arrive at your adjusted model 3) Improvements to the written text and flow 4) Adjustments to the Tables and Figures (see Reviewer 2's comments) to ensure that only the most relevant and applicable information is included and the tables and figures are supportive of the main study objectives. Please submit your revised manuscript by Oct 01 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:
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, Tom E. Wingfield 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 [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: Partly 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: No 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: See attached file: Major Revisions - Statistical Analysis in Methodology � Please mention clearly that you first performed bivariate analysis, and whether thereafter included variables with p value < 0.05 � Please clarify whether, and which, variables were included or excluded a priori from the multivariate analysis to clarify the model building process � Please specify which confounders were included in the analysis here, and which (if any) registry variables were excluded - Descriptive Analysis � Were any other variables excluded due to missing data? Would be helpful to specify % of missing data here � Figure 1: Can you clarify why you decided to exclude 396 individuals with INH resistant TB? Did you perform a separate analysis which included this group to see how outcomes differed? � Table 1: How and why did you choose to disaggregate age into <20, 20 to 39, 40 to 59 and over 60 – it appears the majority are in the 20-59 bracket and valuable information may be lost by grouping into such large categories. Did you perform a sensitivity analysis using smaller age intervals? � There are only 16 patients with XDR TB; are you convinced this sample is large enough to make meaningful conclusions about the rate of unfavourable treatment outcomes in this group? � Please rationalise why you have included method of diagnosis in your analysis, how do you anticipate this would be associated with treatment outcome? - Results: Treatment outcomes and factors associated with Unfavourable outcomes � Consider using primary healthcare as reference group in this analysis; it seems unsurprising here that primary healthcare is a ‘protective factor’ as surely this variable is just a proxy for patients being ‘less sick’. I would be more interested to see whether those receiving secondary/tertiary level care had better or worse outcomes – does being in a tertiary centre result in more specialised care or are patients sicker? - Discussion � ‘The strong association between health regime and TB treatment outcomes in Colombia is relevant, as individuals affiliated with the government-subsidized health regime, i.e., the poorest and most vulnerable population, had a higher probability of presenting unfavourable treatments’ and ‘The conditions of poverty and vulnerability of the population affiliated with the subsidized regime may be associated with different barriers accessing basic and health services’ - This feels like a leap; given your model does not include household income, education level, living conditions – isn’t qualifying for subsidised healthcare a proxy for socioeconomic deprivation in this analysis? It may be difficult to confirm whether the discrepancy in treatment outcome for this group relates to barriers to access, quality of care, or other social factors for unfavourable outcome. Consider rephrasing and discussing these limitations more fully. � ‘Therefore we carry out a careful adjustment of possible confounding factors, seeking to reduce biases’- what kind of bias did you seek to reduce, and what other confounders should have been included? Please explain how your results may have been affected (e.g. over/underestimation of odds ratios) by these confounders being omitted � I think you need to address other limitations to this study e.g. limited sample size, lack of household level characteristics, lack of information on the preceding treatment regimen, and other confounding variables e.g. markers of socioeconomic deprivation and education which are not recorded in this registry, and limited information provided about ethnicity and race. Might be helpful to consider who is not captured by this registry - Conclusions � Try to align the conclusions more closely with your results and discussion Minor Revisions - Title � Could be tweaked to correspond directly to its contents, there is some interchangeable reference between MDR-TB, DR-TB, XDR-TB, RR-TB and RMP. Would also be good to specify that it is a retrospective cohort study and registry based in the title - Abstract � Background: could you clarify what you mean by ‘exerts great pressure on the complex Colombian health system’, e.g. interesting to know whether you are referencing treatment costs, lengthy treatment, inadequate infrastructure? � Methodology: If able please specify the study inclusion criteria, and that the study uses registry level data in the abstract. Are you including those who have received previous treatment? � Results: Language used in the results is inconsistent with the methodology in the abstract, would be helpful to review the sentences ‘511 patients who started treatment for MDR/RR-TB’ and ‘A total of 511 patients were diagnosed with RR-TB in Colombia’. Suggest reviewing the language ‘affiliated with the subsidized health regime’, for example could state ‘individuals who qualified for subsidised health care services’ � Consider making it clearer in the abstract whether you included all patients with DR-TB in your regression model, or whether you performed sub-group analysis comparing MDR-TB, RMP and XDR-TB � Suggest reviewing key words to ensure they relate more closely to your paper, e.g. consider dropping ‘associated factors’ - Introduction � Suggest rephrasing ‘these conditions represent public health problems around the world’, and relating more directly to the challenge that DR-TB poses � Line 61 – are these definitely marked ‘improvements’? � Suggest potential restructuring, and position paragraph 3 first – strengthen argument as to why this is a particular public health concern in Colombia � Please ensure that in-text citations are inside of the sentence, e.g. before full stop. � ‘In 2018, 205 67 cases were notified out of an estimated 580, for a detection rate of 35.3%, similar to 68 the detection rate of 32% reported worldwide’ – please clarify which cases you are referring to; it sounds like you suspect there is underreporting of DR-TB in Colombia? � Several references to ‘pressure’ and the ‘complex Colombian health System’ – please clarify in which respect, e.g. are you referencing lack of resources, infrastructure, workforce? � Suggest maintaining consistent language, e.g. stick with treatment, not mentioning pharmacotherapy in the study objective - Methods o Study Site � You may be able to better summarise or condense the provision of healthcare in Colombia by using a figure or schematic � Please confirm whether subsidised healthcare includes additional support, e.g. social protection measures � Suggest paragraph 1 e.g. line 89-93 could be better summarised and more clearly convey the importance of understanding DR-TB in this study setting � Could be helpful to mention earlier that the direct costs of treatment are ‘free’ at point of care, but there are hidden costs � Also please confirm that TB is a notifiable disease in Colombia o Study Type and Population � Please consider specifying whether the dataset was anonymised or de-identified � Helpful to provide exact dates of study time frame, given you later state it might have been too early for treatment outcomes to be recorded for those where its treatment outcome was missing � Please confirm when treatment outcome was recorded (e.g. time to follow-up), and how � Notification and diagnosis are used interchangeably, helpful to stick to one term only as these can mean slightly different things o Statistical Analysis in Methodology � Reconsider the language ‘analyze the interaction’, this does not really reflect the statistical analysis reported in the results – unless you did examine interaction terms? Otherwise suggest ‘to estimate the association between…’ � Please specify which confounders were included in the analysis here, and which (if any) registry variables were excluded o Definition of Terms � Suggest restructuring to first define outcome variables e.g. ‘favourable’ and ‘unfavourable’ and thereafter how DR-TB is defined in Colombia. It is slightly misleading to first define the clinical rationale needed to ‘suspect’ DR-TB, followed by criteria for the diagnosis of DR-TB – as not totally clear on how DR-TB was defined in your study inclusion criteria � Specify what you mean by the ‘Colombian National Policy’ - Results o Descriptive Analysis � Figure 2: Is it necessary to show rates of both favourable and unfavourable treatment outcomes on the same graph? Please include y axis for scale. Consider excluding this figure, I am not sure that it helps to answer the study objective. � What is the derivation of ‘afro-descendant’? Perhaps consider changing to Afro-Colombian. Who comprises the ‘other’ group – it seems this is the ‘majority’ – How has ethnicity been defined here? � Reconsider phrasing ‘first’, ‘second’ and ‘third’ care as ‘primary’, ‘secondary’ and ‘tertiary’ � On line 211, please reconsider ‘were affiliated with the subsidized social security and health regime’. Does the subsidised health care also include social protection and other welfare benefits? This contradicts the earlier definition o Treatment outcomes and factors associated with Unfavourable outcomes � Describing ‘the treatment success rate with respect to age showed an inversely proportional trend’ seems like a bit of a leap; could be worth rephrasing, and focussing on the needs of this group more in your discussion � Table 2: Given you have performed a binomial logistic regression e.g. with a dichotomous outcome variable not multinomial logistic regression, it feels misleading to show success vs. abandonment vs. failure vs. death in Table 2, consider formatting Table 2 with favourable vs. unfavourable outcomes. Please amend ‘IC95%’ to ’95% CI’. Consider rearranging the reference group to first sub-group for every covariate of interest. Please avoid using commas as decimal points. Please include ‘Ref.’ in your figure legend. Do you think that the ‘self-identified ethnicity’ variable is limited in its use here? - Discussion � Suggest condensing paragraph one and focussing more on your own results and placing them into context, e.g. in the region and then globally � ‘Notably, the diagnosis and treatment of MDR/RR-TB in Colombia is free for all patients regardless of health regime affiliation’ – so actually we are seeing the impact of hidden costs of treatment here? Worth clarifying what is and is not included in your treatment if you are in the subsidised group. Would be helpful to include some background as to catastrophic health spending in Colombia for patients with TB, or more broadly (https://www.researchgate.net/publication/50228851_Determining_factors_of_catastrophic_health_spending_in_Bogota_Colombia) � ‘At the national level, incidence and mortality rates, adjusted for age and sex, were higher for the subsidized regime in 37 events of public health interest’ – please clarify what these 37 events are? And how meaningful is this if incidence and mortality has only been adjusted by age and sex. � ‘Other countries such as Nigeria also documented a higher rate of successful TB treatment among patients treated in the private sector’ – however being treated in a public healthcare facility was not independently associated with unfavourable treatment outcome in your multivariate analysis– so I think this comparison may be limited. Are there any other comparable studies in South America? � ‘The care received at first-level HCIs (health centers) was a protective factor for unfavorable outcomes’- Again this did not persist on adjustment in your multivariate model, and it could be worth exploring this further in your discussion � Please consider using sub-headings in the discussion to clearly structure this section - Conclusions � Please consider rephrasing ‘This high rate of unfavourable treatment outcomes was associated with affiliation with the subsidized health system regime and age ≥ 60 years.’ - e.g. could be adapted to: Those who qualified for subsided health care or who were aged over 60 years were independently more likely to experience unfavourable treatment outcomes Reviewer #2: Dear Authors, the study “Factors associated with unfavorable treatment outcomes in patients with rifampicin-resistant tuberculosis in Colombia” has used a nationwide data on drug resistant TB in Colombia and the analysis are adequate for the research question. Nevertheless, the methods and results should be better described to evaluate some important aspects of data analysis. Also, the discussion could include a better literature review between poverty and unfavourable treatment outcomes, as the main study result show that people that are poor and therefore are being treated in the public healthcare sector in the country are less likely to complete treatment. Please see the suggestion below: Major points 1. In page 5 the authors make a comprehensive description of Colombian health system and describe that all TB treatment is provided for free through the Colombian government (TB programme). Nevertheless, later they include a variable that divide health regime in “subsidized” or “contributive”. I think the authors maybe should make more clear (if what I understood is correct) that independent of the type of health regime, after being diagnosed, the treatment is provided for free. Also, it would be nice to know if this measure is more likely to a proxy of socioeconomic status than the treatment provision itself. 2. In page 6/7, study type and population, please describe the inclusion and exclusion criteria. 3. In page 7, row 126/127: the sentence is confusing. Maybe only say “seventy patients with unknown treatment outcome were excluded”? Also, this also should be moved to the results section. 4. In the methods section, it would be important to include a subsection describing the variables that were extracted from the TB dataset and with which purpose. 5. In page 7, row 125-133: what method was used to include variables in the adjusted model? Backward, forward or the variables were included all at once? The authors considered any confounding variable. 6. In page 7, row 125-133: Some variables included in the results section were not described in the methods. Please include a general description of variables in the adequate section 7. In page 7, row 125-133: how missing data was handled in the analysis? 8. In the methods section, the definition of terms should be included before the statistical analysis. 9. In page 8, row 156-175: the authors are repeating the definitions of treatment outcomes multiple times in the paragraph. Maybe try to be briefer for the readers to follow. 10. In page 8, row 171-175: outcomes not evaluated were included or excluded from the analysis? This should be clear in the methods. 11. In page 9, descriptive analysis, it would be important to describe if there was an increase or decrease in the number of RR-TB over time. 12. In page 9, descriptive analysis, the authors could describe the percentage of cases newly diagnosed and those who are being retreated. 13. In table 1 and 2, the authors included the diagnosis method as a possible explanatory variable for unfavourable treatment outcomes. What is the hypothesis behind including such a variable? 14. Table 1 is secondary for the authors research question. Maybe it should be moved to supplementary material. 15. In Table 2, please describe which ethnicities were included in the “other” category. 16. Figure 2 is not very adequate to show what the authors meant. Maybe a simple one bar graph for each city with the proportions of favourable vs unfavourable outcomes and the N on the top would be clearer. Also, if possible, it would be relevant to know the proportion of RR-TB among all TB cases in each city once the N of RR-TB depends on the number of overall TB cases and the population of each city. 17. In page 13, row 230: did the authors tested for trend in the relationship between age and lower treatment success? 18. In page 17, row 269-271: this sentence is confusing. 19. In the discussion section, the authors make a very important comparison of the study results with other Colombian literature, but have made a limited comparison with the literature from other LMIC countries or elsewhere. For example, if being treated in the private sector is a proxy of wealth, which other studies have shown an association between wealth and poor treatment outcomes? 20. In the limitation section, absence of further socioeconomic data should be included as a limitation for controlling for confounder in the analysis. There is a vast literature showing the relationship between poverty and unfavourable treatment outcomes, as well the effect of poverty reduction measures on improving TB treatment (PMID: 31000126, PMID: 30740248, PMID: 26884501). 21. In the conclusion, the authors should try to demonstrate how the study can be used for policy making or for improving health of those most needed or for improving treatment, or which further research questions are needed. 22. The paper should be revised by a native English speaker. Minor points 1. In the abstract, it is important to make it more clear for the readers what “affiliated with the health regime” means. 2. In page 4, rows 57 – why these conditions represent public health problems? 3. In page 5, row 78 – the word complex does not mean much. The system is complex or the authors meant something else? it would be good to use a more specific word. 4. In page 7, row 127: maybe is more accurate to say descriptive analysis instead of frequency analysis? 5. In page 7, row 130: A logistic regression model was used to analyze the “association” and not the “interaction” between variables. 6. In page 8, row148-153: Please describe all the full names before using abbreviations for the first time (eg. RMP, INH and please check in the text.) ********** 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: Yes: Louisa Chenciner Reviewer #2: Yes: Julia M Pescarini [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.
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| Revision 1 |
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PONE-D-20-18648R1 Factors associated with unfavourable treatment outcomes in patients with rifampicin-resistant tuberculosis in Colombia 2013 - 2015 a retrospective cohort PLOS ONE Dear Dr. Chaves Torres, 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. The reviewers agreed that the manuscript was much improved but there remain areas that still require attention. I would be grateful if you could review both of the reviewers' comments and refine your manuscript accordingly and we then invite you to re-submit for further review. Please submit your revised manuscript by Jan 01 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:
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, Tom E. Wingfield Academic Editor PLOS ONE [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 #1: (No Response) Reviewer #2: 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: Partly Reviewer #2: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ********** 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 Reviewer #2: 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: No Reviewer #2: No ********** 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: I would like to make the following suggestions: Major Revisions: 1. Language - Paper, including abstract, needs revision by native English speaker - Avoid value laden language: examples including lines 60-64 ‘these conditions are generally the consequence’ – implies causality, line 99 ‘marked inequality’, line 109 ‘sheltering all poor and vulnerable people’ – does this policy definitely shelter all?, line 285 ‘Also the patients always incur out-of-pocket expenses’, line 289 ‘in this sense’, line 323 ‘actually influence’, line 324 ‘to rule out confounding factors’, line 334 ‘we believe’ - Aim for consistency in language/terminology used: examples include referencing ‘poor treatment outcome’ vs. ‘unfavourable treatment outcome’; ‘cases’ vs. ‘patients’ in conclusion paragraph - Aim for clear language: examples including lines 221-222 ‘departmental capitals’, concerned that line 134 ‘individualised and anonymous information’ is a contradiction in terms, line 274 ‘differential attention’, line 289 ‘permanence in TB control’, line 233-234 consider rephrasing ‘the older age was associated with a lower success rate, but only patients aged >60 years), line 86-87 ‘different actors’ – are you referencing actors in a health policy setting (e.g. at governmental level) or within the healthcare system?, line 89-90 ‘could help guide the design of national public health strategies’ – could you be more specific here?; line 83 – please clarify which other comorbidities are independently associated with mortality; line 125 ‘obligatory notification’; line 182 ‘logistic regression model was used to analyze’; lines 249-255 ensure distinction is made between odds ratios estimated in bivariate analysis and multivariate analyses; lines 266-267 clarify what you mean by ‘these values’ in the text; consider whether ‘health regime’ or ‘health regimen’ is appropriate use of language - Avoid potentially stigmatising language relating to TB: example including line 138 ‘treatment abandonment’ - Shorten and condense: examples including lines 279-284 could be condensed further - Ensure grammar is correct; lines 124-126 – unclear if these are meant to be two separate sentences? ‘In summary, in Colombia TB is a disease of public health interest. Is of obligatory notification, its diagnosis, treatment and follow-up are covered by public resources’; line 324 ‘However we feel limited the possibility of studying’ 2. Structure and Flow - Suggest review of abstract: including: background to ensure this provides clear rationale for the study, study design, and review of lines 42-45 and methods to ensure brief summary of statistical methods used here - Introduction would benefit from more structured approach, and further review of paragraph order to ensure systematic review is clearly conveyed; Line 78-84 would benefit from revision to distinguish between proximal and distal factors, and to provide context to the variables included latterly in your statistical analysis - Study site section would benefit from review: both paragraph 1 (lines 95-101) and paragraph 2 (lines 102-120) could be condensed further to clearly convey this information to the reader. Thank you for emphasising that those included in subsidised health services are not necessarily included in other social protection programmes; as reviewer #2 mentioned previously it might be helpful to clarify here or later perhaps whether subsidised health services are therefore a proxy for socioeconomic disadvantage. - Definition of Terms; could benefit from restructuring of paragraph 1 (lines 136-143) – to ensure clarity for the reader; e.g. first introduce how the Colombian National Program defines drug resistant TB, and secondly why this may be included in the differential diagnosis and how drug resistant TB may be confirmed -Discussion: I think lines 272-273 could be developed further; e.g. despite free access to MDR/RR-TB, there is discrepancy in treatment outcome and we infer… -Discussion: paragraph consisting of lines 274-284 - this is important information, but it needs to be more closely related to your study findings and results – and condensed as able; lines 292-296 – there seem to be conflicting arguments presented here – e.g. comparison of public healthcare (without social protection) in Colombia compared to protective effect of Bolsa Familia (social protection) in Brazil; in lines 297-306 please link more closely to your study findings; Consider rephrasing rationale for the analysis used in lines 320-324; Please condense lines 330-333, or divide into two shorter sentences; revise sentence on line 337-338 (several clauses used) Minor Revisions: 1. Avoid abbreviations if able in abstract, and ensure all abbreviations used are defined in brackets, but also please avoid duplicate definitions – see line 57 and line 66 of MDR TB 2. Would be helpful to know the precise dates for study inclusion criteria – see line 130 3. Could you clarify why data on treatment outcome was only ‘collected until December 2017’ – see line 131? 4. Suggest providing a citation for how treatment outcome was defined – see line 157-158 5. Could you clarify ‘Seventy patients categorized as not evaluated were not included in the analysis because the treatment outcome was unknown’ – were these missing treatment outcomes, or not yet recorded as a result of the December 2017 cut-off? 6. Thank you for clarifying that you did not include or exclude a priori 7. Suggest formatting throughout (n =; %) – especially noted in lines 216-223; line 229 – ‘87 (19.7)’ need to include ‘%’ for consistency 8. Ensure formatting consistent in Table 1; use decimal points not commas, consider use of bold for reference category/sub-heading; ensure all in English language ‘Menor de 20’ 9. Avoid inclusion of odds ratios in discussion (should mostly feature in results) 10. In references, for online resources please provide access/citation date Reviewer #2: Dear authors, the manuscript improved substantially since the last submission but I believe some further improvements to the abstract and introduction would be desirable so the paper could reach a larger audience. The manuscript would also benefit from a nice public health message. Please see some comments below: Major 1. The abstract could be revised. The methods section is lacking substantial information on: the variables, outcome definition, statistical methods used for the analysis. Similarly, there is substantial repeated information in the introduction, methods and results. In the conclusions section, the authors could also include some practical application of the results for targeting policies that reduce these health inequalities in Colombia. 2. Introduction - Rows 73-77. This is an interesting paragraph, but hard to follow and not related to the specific objective of the study. I suggest that this bit is removed to give flow to the introduction. 3. Introduction - The authors do not show the readers the current research gaps that this study aim to fulfil. 4. Methods - Page 186, it is still not clear if the authors included all the variables with p<0.05 in the bivariate analysis in the multivariate analysis, without testing for interactions, collinearity, or significance. The authors explained their criteria in the discussion, but it would be clearer in the methods section. 5. Methods- In row 220, why there is 67.8% who were affiliated with the subsidized health regime but only 63.7% were treated in “public HCIs”? Public institutions attend both individuals under the subsidized Individuals and the contributory system? If these variables are very correlated (as explained in the discussion), would not be important to choose only one for the multivariate analysis. 6. In the conclusions section, the last paragraph lack of a public health message that interprets or suggests 7. Please include a "Data Availability Statement" Minor 7. In the introduction, row 63, when listing the reasons the “and” is missing. 8. In the introduction, Row 69, please replace incidence for either “incident cases”. 9. In row 71, substitute “16,000 estimated cases” by “approximately 16,000 cases” 10. In Table 1, please include the N´s for the columns: “Favourable (N=XX)” and “Unfavourable (N=XX)” 11. Table 1, row “Male”, please change the comma for a point. Check commas used instead of points 12. Figure 1 title, please change “Flow chart” for “flowchart”; Please consider using a title that describes better the figure, e.eg., “Flowchart with selected studied population with MDR/RR-TB in Colombia…” ********** 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: L Chenciner Reviewer #2: Yes: Julia Pescarini [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.
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| Revision 2 |
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PONE-D-20-18648R2 Factors associated with unfavorable treatment outcomes in patients with rifampicin-resistant tuberculosis in Colombia 2013 – 2015: A retrospective cohort study PLOS ONE Dear Dr. Chaves Torres, Thank you for submitting your revised manuscript to PLOS ONE. After careful consideration, we feel that it has merit but still does not fully meet PLOS ONE’s publication criteria as it currently stands. In particular, while Reviewer #2 is happy with your revision, Reviewer #1 still made comments and suggestions for improvement. Therefore, we invite you to submit a further revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Mar 05 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:
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, Olivier Neyrolles Academic Editor PLOS ONE 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) Reviewer #2: 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: Partly Reviewer #2: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 Reviewer #2: 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: No Reviewer #2: 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: Dear Dr Chaves Torres, Many thanks for your most recent submission, entitled 'Factors associated with unfavourable treatment outcomes in patients with rifampicin resistant tuberculosis in Colombia 2013 – 2015: A retrospective cohort study' and for the opportunity to review your work. I have attached more detailed feedback, and have structured my comments using minor and major criteria. The introduction, methodology and conclusion sections would particularly benefit from further review. I look forward to your revised submission - Kind regards, Dr Louisa Chenciner Reviewer #2: Dear authors, I appreciate the opportunity to revise this interesting piece of work that highlight its importance for TB control policies among the poorest in Colombia and that bring light to the problem of underfinacing of public healthcare systems in Latin America. ********** 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: Louisa Chenciner Reviewer #2: Yes: Julia M Pescarini 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.
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| Revision 3 |
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PONE-D-20-18648R3 Factors associated with unfavorable treatment outcomes in patients with rifampicin-resistant tuberculosis in Colombia 2013 – 2015: A retrospective cohort study PLOS ONE Dear Dr. Chaves Torres, Thank you for submitting your revised manuscript to PLOS ONE. Your manuscript will be accepted for publication once you have addressed the remaining comments raised by Reviewer #1, which are only dealing with style and typos. Therefore, we invite you to submit a final revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Apr 11 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:
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, Olivier Neyrolles Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. 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) ********** 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: No ********** 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: Dear Authors, Many thanks for your revised submission, and for your continued efforts to refine and improve this manuscript. Please see attached PDF for detailed comments and recommendations to ensure the manuscript is written in standard English, and avoids potentially stigmatising language with respect to TB. Kind regards, Dr Louisa Chenciner ********** 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: Louisa Chenciner [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.
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| Revision 4 |
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Factors associated with unfavorable treatment outcomes in patients with rifampicin-resistant tuberculosis in Colombia 2013 – 2015: A retrospective cohort study PONE-D-20-18648R4 Dear Dr. Chaves Torres, 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, Olivier Neyrolles Section Editor PLOS ONE |
| Formally Accepted |
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PONE-D-20-18648R4 Factors associated with unfavorable treatment outcomes in patients with rifampicin-resistant tuberculosis in Colombia 2013 – 2015: A retrospective cohort study Dear Dr. Chaves-Torres: 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. Olivier Neyrolles Section Editor PLOS ONE |
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