{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:07:30Z","timestamp":1772168850239,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.125815.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T00:00:00Z","timestamp":1721692800000}}],"reference-count":31,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T00:00:00Z","timestamp":1721692800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000200","name":"United States Agency for International Development","doi-asserted-by":"publisher","award":["72038620CA00012"],"award-info":[{"award-number":["72038620CA00012"]}],"id":[{"id":"10.13039\/100000200","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"\n Background<\/ns3:italic>\n Tuberculosis (TB) continues to pose a serious threat to the public health system in India. Although the National Tuberculosis Elimination Program (NTEP) is providing a wide range of interventions from early diagnosis to complete treatment to reduce morbidity and mortality from TB, adverse drug reactions (ADR) remain a challenge in treatment adherence and completion.\n Methods<\/ns3:italic>\n An observational cross-sectional study was conducted in selected districts of Gujarat state. A total of 593 reported TB patients were recruited with an adjusted unified distribution based on the type of cases, site of diseases, and service facility through a simple random sampling method. A semi-structured questionnaire tool was used to collect socio-demographic, clinical, and ADR-related data from the TB patients. Data was analyzed for the frequency, percentage, chi-squared, and adjusted odds ratio to find the association between the variables.\n Results<\/ns3:italic>\n The majority of the study participants were male (87.2%), aged 15 to 60 (57.8%), daily laborers (22.4%), and married (64.2%). Over 75% of individuals had pulmonary TB, with 87% having experienced their first episode, 83% being new cases, and 44.7% having a history of addiction. ADR with mild symptoms was reported by more than a quarter (29%) of TB patients during the intensive phase (77%). The association between ADR experience and drug susceptibility was significant (p<0.005) and drug-resistant TB patients experience two times more ADRs than drug-sensitive TB patients (OR 2.04). Binomial logistic regression was carried out to describe the association between various variables and occurrence of ADRs.\n Conclusion<\/ns3:italic>\n The study highlighted a need to enhance health care providers\u2019 capacity and program structure for managing ADRs among TB patients. In order to completely eliminate TB across the country, it also emphasized the attention for a holistic and all-encompassing strategy for managing TB patients at the field level.\n <\/ns3:p>","DOI":"10.12688\/f1000research.125815.2","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T13:00:24Z","timestamp":1721739624000},"page":"1388","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Characteristics and contributing factors of adverse drug reactions: an analytical study of patients with tuberculosis receiving treatment under the National TB Program of India"],"prefix":"10.12688","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3349-7562","authenticated-orcid":false,"given":"Harsh","family":"Shah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1770-8745","authenticated-orcid":false,"given":"Sandul","family":"Yasobant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1486-0821","authenticated-orcid":false,"given":"Jay","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priya","family":"Bhavsar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8043-3388","authenticated-orcid":false,"given":"Somen","family":"Saha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yogesh","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak","family":"Saxena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anish","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2024,7,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"001-003","DOI":"10.4103\/0974-2727.154778","article-title":"Challenges in Tuberculosis Diagnosis and Management: Recommendations of the Expert Panel.","volume":"7","author":"S Singh","year":"2015","journal-title":"J. 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Res."},{"key":"ref32","doi-asserted-by":"publisher","author":"H Shah","year":"2022","DOI":"10.6084\/m9.figshare.21185875.v1"}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T07:10:11Z","timestamp":1739517011000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,23]]},"references-count":31,"URL":"https:\/\/doi.org\/10.12688\/f1000research.125815.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.125815.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.169379.r306199","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.169379.r361948","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.169379.r305305","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.169379.r361948","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.169379.r305305","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.169379.r306199","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,23]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.169379.r306199, Gyanshankar Mishra, Indira Gandhi Government Medical College, Nagpur, Maharashtra, 19 Aug 2024, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2#referee-response-306199","order":0,"name":"referee-response-306199","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.169379.r305305, Aditi Gupta, Pulmonary Medicine, BRAIMS, Mohali, 25 Jul 2024, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2#referee-response-305305","order":1,"name":"referee-response-305305","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Harsh Shah<\/b>; \nPosted: 25 Jul 2024<\/i>; Greetings, Reviewer We appreciate your input, however we would like you to review the response that addresses the comments you expressed regarding the manuscript. We believe that the evidence that this article generates will be necessary to improve India's ADR surveillance system as part of the National TB Elimination Program. 1. Kindly elaborate Serious adverse events (SAE) and ADR categories also need to be explained The study had classified ADRs into various categories based on severity, including mild, moderate, and severe, with SAEs defined as those resulting in significant health risks, requiring hospitalization, or leading to long-term consequences. This classification is based on the guidelines and protocols defined in context with the National TB Elimination Program (NTEP). 2. It has been proven that elderly develop more ADR but this is not the case with your study. While literature indicates a higher prevalence of ADRs among elderly patients, the findings may reflect demographic variances or differences in treatment regimens that could mitigate these risks. It is crucial to consider that the elderly in the study may have had different TB comorbidities or medication profiles compared to the general population. The results provide valuable insights into the complexity of ADRs and underscore the need for targeted interventions in vulnerable groups. 3. BMI, age, comorbidity have strong association with ADR. Given tables and text do not support this. While the study did not establish significant correlations in the reported data, it is important to consider that these associations can vary based on geographical and socioeconomic factors affecting the patient population. The findings contribute to the broader understanding of ADRs in TB treatment and highlight the necessity for ongoing research to explore these relationships further, particularly in public health settings where such data can inform resource allocation and management strategies. We made references supporting this evidences, however we believe there should be more in depth operational research or longitudinal case control study will provide more structured findings in alignment of the NTEP in India.  4. Kindly elaborate, how did you reach private patients for interview. We reached out the private patients through the National Tuberculosis Elimination Program (NTEP) staff, project staff and through various stakeholders, to ensure a comprehensive representation of persons with TB across both public and private healthcare sectors. 5. Since, there is lot of recall bias, results cannot be generalized. While we acknowledge that recall bias can affect data accuracy, we have already mentioned and narrated it under the limitation of the study. In order to reduce the recall bias, we had further employed a semi-structured questionnaire designed to mitigate these issues by prompting patients to recall their experiences in the context of their ongoing \/ completed treatment. We ensured that the interviewed study subjects have the medical records available in Ni-kshay or with treatment report card at health facilities in case of requirement to check bias.    6. At what time of treatment, did you interview the patient? Time of interview is very important in assessing ADR and decreasing recall bias. Ideally different groups at different time point of treatment must be evaluated or even same group at different time points if feasible. The study interviews were conducted from the individuals with TB on post completion \/ on going of their TB treatment. We have tried to incorporate various representative of patients in the study to understand the occurrence of ADRs at various phase of treatment. We could not make separate groups in absence of budgetary restriction to repeat visits for periodic timeframe. The study design was cross sectional and interview was one time event. This is limitation that we have mentioned into the manuscript. 7. Design of the study makes it very less informative. While the design may appear limited, it was intentionally developed to capture data from a diverse patient population. The findings provide critical insights into ADRs experienced by individuals undergoing TB treatment at point interval (with cross sectional design), which is vital for program policies aimed at improving drug safety and efficacy. The study highlights the importance of monitoring ADRs during various treatment phases, which is essential for developing effective TB interventions that ensure patient safety and optimize treatment outcomes. Kindly do revisit the manuscript and comments that we addressed here.  Regards","URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2#referee-comment-12073","order":2,"name":"referee-comment-12073","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.169379.r361948, Anurag Agarwal, Maulana Azad Medical College & Associated Hospitals, New Delhi, 07 Feb 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2#referee-response-361948","order":3,"name":"referee-response-361948","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Harsh Shah<\/b>; \nPosted: 13 Feb 2025<\/i>; Responses from the Authors based on Reviewer Comments 1.    First-line ATT and second-line ATT adverse effects are not comparable and should be handled separately since drugs, duration of treatment, and the number of drugs differ significantly. o    We appreciate the reviewer\u2019s observation. In section 3.3; we have mentioned that out total who were on second line ATT, 18 (56%) reported ADRs and 50% of whom reported moderate and severe ADRs. The second line ATT have been already having higher side of ADRs; however, during the study, we would like to focus on public health perspective of addressing ADRs identification and subsequent management; especially at the Sub center and Primary Health Center Level.  2.    A comparison of ADRs within weight bands could have been made. Was there any relation to weight in the individual weight band? o    This is a valuable suggestion. While our study did not specifically analyse ADRs in relation to weight bands, we acknowledge its importance and will consider investigating this aspect in a future study focusing on individual patient characteristics and weight-based variations in ADR occurrence. 3.    Was there an increase in adverse events after shifting to daily ATT vs. the previous alternate-day ATT? o    Since our study was conducted after the implementation of the daily ATT regimen, we do not have comparative data on ADR intensity between daily and alternate-day regimens. A comparative study assessing ADRs before and after this policy change would be required to draw such conclusions. 4.    Hospitalization, temporary or permanent drug stoppage, and mortality should have been recorded. o    In Section 3.3 \u2013 we have mentioned that during the study, it was observed that 172 (29%) patients experienced ADRs with at least one symptom. Out of those, 80% had mild symptoms, and 133 (77%) experienced them during the early (intensive) phase of the treatment initiation. As 20% had reported moderate to severe ADRs, we had collected information capturing detailed clinical outcomes such as hospitalization, drug discontinuation, or mortality; however, we could not validate with case records so we have not included those details.  We recognize the significance of these data variables and will consider incorporating them in future research that specifically evaluates ADR-related outcomes. 5.    How was it concluded that "The analysis delivered crucial conclusions that could direct policymakers to educate and train all healthcare professionals and high-risk patients on how to solicit and manage ADRs among patients receiving programmatic treatment effectively\u2026"? This was not the aim or purpose of the study nor was it looked at in the study. o    We appreciate this insight. While the primary objective of our study was to analyse ADRs due to ATT, our findings also highlighted the need for improved ADR management at the community level, especially at ASHA and Health and Wellness Center Level. Based on interviews and observations, we found that many ADRs could be managed with simple timely interventions, reducing unnecessary treatment discontinuation. This reinforces the need for structured training programs for healthcare providers and treatment supporters, ultimately improving treatment adherence and programmatic outcomes. We thank reviewer for providing the valuable comments.","URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2#referee-comment-13341","order":4,"name":"referee-comment-13341","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.138161.r235640, Yogendra Shah, Province Public Health Laboratory, Kailali, 10 Feb 2025, version 1, 2 approved with reservations, 1 not approved","URL":"https:\/\/f1000research.com\/articles\/11-1388\/v1#referee-response-235640","order":5,"name":"referee-response-235640","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Harsh Shah<\/b>; \nPosted: 13 Feb 2025<\/i>; \n1.<\/b> Revise the title to align more closely with the manuscript's research objectives. We have received feedbacks from other reviewers' and based on this we had uploaded version 2 already. The comments received on Version 1.  \n2.<\/b> Summarize only the significant findings in the abstract, including background, rationale, and justification of the study. The abstract summarizes key findings within the journal\u2019s structured format, covering background, methods, results, and conclusions. We have matched as per journal's criteria.  \n3.<\/b> Select crucial keywords from the abstract. Already Included as per Journal's criteria.  \n4.<\/b> \nIntroduction<\/b> a. Provide a brief overview of the global situation concerning \nMycobacterium tuberculosis<\/i> complex, with a specific focus on the current status in India. Already included in Version 2.  b. Discuss the utility of phenotypic and genotypic techniques in diagnosing TB globally. Since the manuscript focuses on ADRs associated with ATT, an in-depth discussion on phenotypic\/genotypic techniques and drug-resistant mechanisms is beyond the study\u2019s objectives. We will consider these aspects for a future study focusing on TB diagnostics. c. Explore possible contributing factors to adverse drug reactions among tuberculosis patients. Same as point \n4b<\/b>. d. Examine drug-resistant genes' mechanisms through genotypic techniques, explaining principles and applications for diagnosing TB and other diseases. The study emphasizes ADRs among individuals with TB from a public health perspective rather than clinical or diagnostic dimensions. As a result, the feasibility of combining epidemiological and genomic data was not explored in this study. e. Clearly justify the research objective and rationale for the current study. The research objective and rationale are outlined in the introduction section of the manuscript. \n5.<\/b> \nMaterials and Methods<\/b> a. Define inclusion and exclusion criteria for confirming TB patients using phenotypic and genotypic methods. The study included individuals with TB who were notified in the Ni-kshay system. Since the research primarily focuses on ADRs rather than TB diagnosis, discussing phenotypic\/genotypic confirmation criteria would shift the study\u2019s focus. b. Outline procedures for phenotypic methods and genotypic methods. Consider creating a flowchart illustrating the study design. The study does not involve laboratory-based diagnostic procedures but rather evaluates ADRs associated with ATT. Therefore, outlining phenotypic methods is beyond the study\u2019s scope. c. Provide a straightforward discussion of procedures and statistical analyses in an easily understandable format. The methodology is clearly described in a straightforward manner to ensure comprehensibility. If specific sections require further clarification, we are open to refinement. d. Elaborate on the procedure for studying drug-resistant TB isolates and the use of artificial intelligence software for vaccine development against TB. The study does not focus on drug-resistant TB isolates or AI-driven vaccine development. These aspects would be more relevant to a study centered on TB diagnostics and treatment innovation. \n6.<\/b> \nResults<\/b> a. Restructure and discuss results in a sequential order for better comprehension. The results have been presented in a logical, self-explanatory sequence to ensure clarity. However, we are open to suggestions for minor restructuring if needed. b. Compare various databases for studying mutations in resistance genes to first and second-line anti-TB drugs. The study does not analyze genetic mutations in resistance genes. This aspect is outside the study\u2019s scope, which focuses on ADRs associated with ATT. c. Highlight key findings in tables and provide brief explanations. Use asterisks to denote P<0.05 significance in tables. Already included in Manuscript Version 2. \n7.<\/b> \nDiscussion<\/b> a. Revise the entire discussion section, comparing the current paper's findings with those of previous global studies. The discussion was initially drafted in 2022, reflecting the data collected in 2021. Updating it with the most recent global studies may shift the contextual framework and compromise the consistency of findings. b. Include a discussion on the limitations of the research study. The limitations of the study are clearly stated in the limitation section of the manuscript. c. Conclude with comprehensive recommendations grounded in practicality rather than theory. The recommendations are grounded in public health applicability and designed for practical implementation at the community level. d. Implementing the current study involves carefully following the research plan outlined in your manuscript. Here is a step-by-step guide on how to implement the study: The study comprehensively captures ADRs and associated factors among individuals with TB. We were unable to access the step-by-step guide referenced in the editorial comments, but we are open to aligning our methodology with any additional clarifications provided.","URL":"https:\/\/f1000research.com\/articles\/11-1388\/v2#referee-comment-13342","order":6,"name":"referee-comment-13342","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study is made possible by the generous support of the American people through the United States Agency for International Development (USAID) (Co-operative Agreement no. 72038620CA00012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":7,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}