{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T19:07:28Z","timestamp":1754161648035,"version":"3.41.2"},"reference-count":17,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"unspecified","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,6,19]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Tuberculosis (TB) remains a major public health challenge in Sub-Saharan Africa, exacerbated by the high prevalence of drug-resistant TB (DR-TB) and its strong association with HIV. Bedaquiline (BDQ), approved by the WHO in 2013, offers a promising treatment for DR-TB, including multidrug-resistant TB (MDR-TB) and extensively DR-TB (XDR-TB). However, BDQ has been associated with QT interval prolongation, a condition that can lead to serious cardiac arrhythmias such as torsades de pointes. This systematic review and meta-analysis aims to quantify the incidence of QT interval prolongation in patients receiving BDQ for DR-TB in Sub-Saharan Africa and identify predictors of this adverse effect.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>We will conduct a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science and African Journals Online using medical subject headings and keywords related to \u2018BDQ\u2019, \u2018DR-TB\u2019, \u2018QT interval prolongation\u2019 and \u2018Sub-Saharan Africa\u2019. Eligible studies will include randomised controlled trials, cohort studies, case-control studies and observational studies conducted in Sub-Saharan Africa. Study titles and abstracts will be initially screened, and full texts will be retrieved and reviewed against eligibility criteria. Relevant data will be extracted from the selected articles and assessed for risk of bias. The primary outcome will be the pooled incidence of QT interval prolongation. Data will be synthesised using a random-effects model meta-analysis if significant heterogeneity is present; otherwise, a fixed-effects model will be applied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>This study will use published data, requiring no ethical approval. Findings will be disseminated through peer-reviewed publications and conference presentations to inform clinical guidelines and DR-TB treatment policies in Sub-Saharan Africa.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PROSPERO registration number<\/jats:title>\n                  <jats:p>CRD42024560368.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-096709","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T05:40:13Z","timestamp":1753767613000},"page":"e096709","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Incidence of QT interval prolongation in patients receiving bedaquiline for drug-resistant tuberculosis in Sub-Saharan Africa: a protocol for systematic review and meta-analysis"],"prefix":"10.1136","volume":"15","author":[{"given":"Morrish","family":"Okello-Obol","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Gulu University, Gulu, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0768-1315","authenticated-orcid":false,"given":"Ivaan","family":"Pitua","sequence":"additional","affiliation":[{"name":"School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James Nelson","family":"Okema","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Gulu University, Gulu, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doris","family":"Ekwem","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, St. Mary\u2019s Hospital, Lacor, Gulu, Uganda"},{"name":"School of Health Sciences, Cavendish University, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4515-8517","authenticated-orcid":false,"given":"Felix","family":"Bongomin","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Gulu University, Gulu, Uganda"},{"name":"Department of Internal Medicine, Gulu Regional Referral Hospital, Gulu, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Olum","sequence":"additional","affiliation":[{"name":"School of Public Health, Makerere University, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"2025072822400431000_15.7.e096709.1","unstructured":"World Health Organization . Global tuberculosis report. Geneva WHO; 2021. Available: https:\/\/www.who.int\/publications\/i\/item\/9789240037021"},{"key":"2025072822400431000_15.7.e096709.2","unstructured":"MOH Uganda . Republic of Uganda addendum to the national guidelines for the programmatic management of drug-resistant tuberculosis. 2019."},{"key":"2025072822400431000_15.7.e096709.3","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph182010678","article-title":"Tuberculosis Treatment Outcome and Predictors in Africa: A Systematic Review and Meta-Analysis","volume":"18","author":"Teferi","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"2025072822400431000_15.7.e096709.4","article-title":"Multidrug-Resistant TB (MDR-TB) and Extensively Drug-Resistant TB (XDR-TB) Among Children: Where We Stand Now","volume":"15","author":"Chowdhury","year":"2023","journal-title":"Cureus"},{"key":"2025072822400431000_15.7.e096709.5","doi-asserted-by":"crossref","DOI":"10.3390\/antibiotics8040261","article-title":"Re-Understanding the Mechanisms of Action of the Anti-Mycobacterial Drug Bedaquiline","volume":"8","author":"Sarathy","year":"2019","journal-title":"Antibiotics (Basel)"},{"key":"2025072822400431000_15.7.e096709.6","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02586-16","article-title":"Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis","volume":"61","author":"Arnold","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2025072822400431000_15.7.e096709.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2117166"},{"key":"2025072822400431000_15.7.e096709.8","doi-asserted-by":"crossref","DOI":"10.1186\/s12879-022-07861-x","article-title":"Bedaquiline safety, efficacy, utilization and emergence of resistance following treatment of multidrug-resistant tuberculosis patients in South Africa: a retrospective cohort analysis","volume":"22","author":"Pai","year":"2022","journal-title":"BMC Infect Dis"},{"key":"2025072822400431000_15.7.e096709.9","doi-asserted-by":"publisher","DOI":"10.1136\/bjsm.2008.054734"},{"key":"2025072822400431000_15.7.e096709.10","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(20)30770-2"},{"key":"2025072822400431000_15.7.e096709.11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.4103\/ijmy.ijmy_178_22","article-title":"Scoping Review","volume":"11","author":"Putra","year":"2022","journal-title":"Int J Mycobacteriology"},{"key":"2025072822400431000_15.7.e096709.12","first-page":"9","article-title":"Drug-Resistant Tuberculosis and HIV Infection: Current Perspectives","volume":"12","author":"Singh","year":"2020","journal-title":"HIV AIDS (Auckl)"},{"key":"2025072822400431000_15.7.e096709.13","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med"},{"key":"2025072822400431000_15.7.e096709.14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002742","article-title":"COSMOS-E: Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology","volume":"16","author":"Dekkers","year":"2019","journal-title":"PLoS Med"},{"key":"2025072822400431000_15.7.e096709.15","doi-asserted-by":"publisher","DOI":"10.1136\/jech-2013-203104"},{"key":"2025072822400431000_15.7.e096709.16","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"2025072822400431000_15.7.e096709.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2015.05.009"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-096709","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T05:40:16Z","timestamp":1753767616000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-096709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":17,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,28]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/bmjopen-2024-096709"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-096709","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}