{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:58:51Z","timestamp":1787237931872,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["K24AT009893"],"award-info":[{"award-number":["K24AT009893"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Low arginine bioavailability is associated with vaso\u2010occlusive painful crisis (VOC) severity in sickle cell anemia (SCA) and predicts need for pediatric hospitalization. Intravenous arginine therapy has opioid\u2010sparing effects and was found to significantly decrease pain scores in children hospitalized with SCA\u2010VOC in a phase\u2010two randomized placebo\u2010controlled trial (RCT). Efficacy of oral arginine is unknown. Our objective was to determine the safety and efficacy of oral arginine therapy in Nigerian children with SCA. A double\u2010blind RCT of oral L\u2010arginine\u2010hydrochloride (100\u2009mg\/kg TID) was conducted in children with SCA\u2010VOC, aged 5\u201017\u2009years, hospitalized at two Nigerian sites. The primary outcome measure was analgesic usage, quantified by difference in the mean Analgesic Medication Quantification Scale (MQS). Secondary outcomes included daily pain scores, time\u2010to\u2010crisis\u2010resolution and length\u2010of\u2010hospital\u2010stay. An intention\u2010to\u2010treat analysis was performed. Sixty\u2010eight children (age 5\u201017\u2009years, mean 10.6\u2009\u00b1\u20090.4\u2009years; 56% male), were randomized to receive L\u2010arginine (35 patients) or placebo (33 patients). The mean total MQS for the arginine group was 73.4 (95% CI, 62.4\u201084.3) vs 120.0 (96.7\u2010143.3) for placebo (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u2009.001). The mean rate of decline in worst pain scores was faster in the arginine arm vs placebo (1.50 [1.23\u20101.77] vs 1.09 [0.94\u20101.24] point\/d,\n                    <jats:italic>P<\/jats:italic>\n                    = .009). Children receiving arginine had a shorter time\u2010to\u2010crisis\u2010resolution (\n                    <jats:italic>P<\/jats:italic>\n                    = .02), shorter hospital\u2010stay (\n                    <jats:italic>P<\/jats:italic>\n                    = .002) and experienced no serious adverse event. Pain control was more rapid, total analgesic requirement was significantly reduced, and most notably, time\u2010to\u2010crisis\u2010resolution and length\u2010of\u2010hospital\u2010stay were shorter in children with SCA\u2010VOC receiving arginine vs placebo. Given the established safety and low cost, oral arginine is a promising adjuvant therapy for SCA\u2010VOC management.\n                  <\/jats:p>","DOI":"10.1002\/ajh.26028","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T14:24:50Z","timestamp":1603117490000},"page":"89-97","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Randomized control trial of oral arginine therapy for children with sickle cell anemia hospitalized for pain in\n                    <scp>Nigeria<\/scp>"],"prefix":"10.1002","volume":"96","author":[{"given":"Richard","family":"Onalo","sequence":"first","affiliation":[{"name":"Department of Paediatrics Faculty of Clinical Sciences, University of Abuja  Gwagwalada Nigeria"},{"name":"Department of Paediatrics Faculty of Clinical Sciences, University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Faculty of Clinical Sciences, University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette","family":"Cilliers","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barend C.","family":"Vorster","sequence":"additional","affiliation":[{"name":"Centre for Human Metabolomics North West University  Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nnebe\u2010Agumadu","family":"Uche","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Faculty of Clinical Sciences, University of Abuja  Gwagwalada Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oniyangi O.","family":"Oluseyi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics National Hospital  Abuja Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria D.","family":"Onalo","sequence":"additional","affiliation":[{"name":"Emergency Paediatric Pharmacy University of Abuja Teaching Hospital  Gwagwalada Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunusa","family":"Zubairu","sequence":"additional","affiliation":[{"name":"Emergency Paediatric Pharmacy University of Abuja Teaching Hospital  Gwagwalada Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice U.","family":"Ayodele\u2010Kehinde","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Abuja Teaching Hospital  Gwagwalada Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oladimeji M.","family":"Damilare","sequence":"additional","affiliation":[{"name":"Independent Consultant  Abuja Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Biostatistical Core, Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6019-2858","authenticated-orcid":false,"given":"Claudia R.","family":"Morris","sequence":"additional","affiliation":[{"name":"Division of Pediatric Emergency Medicine, Department of Pediatrics Emory University School of Medicine  Atlanta Georgia USA"},{"name":"Children\u02bcs Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1104"},{"key":"e_1_2_11_3_1","unstructured":"Centers for Disease Prevention and Control. 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