{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:17:45Z","timestamp":1785853065172,"version":"3.56.0"},"reference-count":86,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite ~90% of sickle cell disease (SCD) occurring in low-and middle-income countries (LMICs), the vast majority of people are not receiving evidence-based interventions (EBIs) to reduce SCD-related adverse outcomes and mortality, and data on implementation research outcomes (IROs) and SCD is limited. This study aims to synthesize available data on EBIs for SCD and assess IROs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review of RCTs reporting on EBIs for SCD management implemented in LMICs. We identified articles from PubMed\/Medline, Global Health, PubMed Central, Embase, Web of Science medical subject heading (MeSH and Emtree) and keywords, published from inception through February 23, 2020, and conducted an updated search through December 24, 2020. We provide intervention characteristics for each study, EBI impact on SCD, and evidence of reporting on IROs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Main results<\/jats:title>\n                    <jats:p>29 RCTs were analyzed. EBIs identified included disease modifying agents, supportive care agents\/analgesics, anti-malarials, systemic treatments, patient\/ provider education, and nutritional supplements. Studies using disease modifying agents, nutritional supplements, and anti-malarials reported improvements in pain crisis, hospitalization, children\u2019s growth and reduction in severity and prevalence of malaria. Two studies reported on the sustainability of supplementary arginine, citrulline, and daily chloroquine and hydroxyurea for SCD patients. Only 13 studies (44.8%) provided descriptions that captured at least three of the eight IROs. There was limited reporting of acceptability, feasibility, fidelity, cost and sustainability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EBIs are effective for SCD management in LMICs; however, measurement of IROs is scarce. Future research should focus on penetration of EBIs to inform evidence-based practice and sustainability in the context of LMICs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      This review is registered in PROSPERO #\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD42020167289\" xlink:type=\"simple\">CRD42020167289<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0246700","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T15:47:46Z","timestamp":1613576866000},"page":"e0246700","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Evidence-based interventions implemented in low-and middle-income countries for sickle cell disease management: A systematic review of randomized controlled trials"],"prefix":"10.1371","volume":"16","author":[{"given":"Joyce","family":"Gyamfi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Temitope","family":"Ojo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Epou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotanna","family":"Dike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Adenikinju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scholastica","family":"Enechukwu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4232-9413","authenticated-orcid":true,"given":"Dorice","family":"Vieira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obiageli","family":"Nnodu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gbenga","family":"Ogedegbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Peprah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"issue":"2","key":"pone.0246700.ref001","doi-asserted-by":"crossref","first-page":"021103","DOI":"10.7189\/jogh.08.021103","article-title":"The global burden of sickle cell disease in children under five years of age: a systematic review and meta-analysis","volume":"8","author":"E. 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Neville","year":"2011","journal-title":"18th Expert Committee on the Selection and Use of Essential Medicines"},{"issue":"7","key":"pone.0246700.ref031","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1056\/NEJMoa1512021","article-title":"A Multinational Trial of Prasugrel for Sickle Cell Vaso-Occlusive Events","volume":"374","author":"M.M. Heeney","year":"2016","journal-title":"New England Journal of Medicine"},{"issue":"12","key":"pone.0246700.ref032","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1002\/ajh.24198","article-title":"Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial","volume":"90","author":"J.S. 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Cox","year":"2018","journal-title":"Lancet Haematol"},{"issue":"1","key":"pone.0246700.ref037","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3945\/ajcn.112.036319","article-title":"Effect of omega-3 (n-3) fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-controlled trial","volume":"97","author":"A.A. Daak","year":"2013","journal-title":"American Journal of Clinical Nutrition"},{"issue":"2","key":"pone.0246700.ref038","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4103\/1115-2613.278265","article-title":"Monthly sulphadoxine-pyrimethamine combination versus daily proguanil for malaria chemoprophylaxis in sickle cell disease: a randomized controlled study at the Jos University Teaching Hospital","volume":"25","author":"J.A. 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Silva-Pinto","year":"2019","journal-title":"International Journal of Neonatal Screening"},{"issue":"2","key":"pone.0246700.ref060","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1046\/j.1365-3156.2000.00507.x","article-title":"An open comparative study of dispersible piroxicam versus soluble acetylsalicylic acid for the treatment of osteoarticular painful attack during sickle cell crisis","volume":"5","author":"F.U. Eke","year":"2000","journal-title":"Tropical Medicine & International Health"},{"key":"pone.0246700.ref061","first-page":"136","article-title":"Determining effects of platelet inhibition on vaso-occlusive events (DOVE) trial: A double-blind, placebo-controlled, study of prasugrel in paediatric patients with sickle cell anaemia","volume":"101","author":"M. 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