{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T06:46:16Z","timestamp":1777099576372,"version":"3.51.4"},"reference-count":29,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,17]],"date-time":"2019-11-17T00:00:00Z","timestamp":1573948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","award":["NCT01794000"],"award-info":[{"award-number":["NCT01794000"]}],"id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005927","name":"Daiichi Sankyo Foundation of Life Science","doi-asserted-by":"publisher","award":["NCT01794000"],"award-info":[{"award-number":["NCT01794000"]}],"id":[{"id":"10.13039\/501100005927","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: DOVE (Determining Effects of Platelet Inhibition on Vaso-Occlusive Events) was a Phase 3, randomized, double-blind, placebo-controlled study conducted in children with sickle cell anemia at 51 sites in 13 countries across four continents. Procedure: Data from DOVE were assessed for regional differences in subject phenotype and treatment. Demographics, baseline clinical and laboratory data, hydroxyurea (HU) use, vaso-occlusive crisis (VOCs; composite endpoint of painful crisis or acute chest syndrome (ACS)), serious adverse events (SAEs), hospitalization, and treatments were compared across the Americas, Europe, North Africa\/Middle East, and Sub-Saharan Africa (SSA). Results: Race, body mass index, and blood pressures differed by region. Pre-enrollment VOCs were highest in the Americas. For subjects not on HU, baseline hemoglobin was lowest in SSA; reticulocyte count was lowest in the Americas. Within SSA, Kenya subjects presented higher baseline hemolysis. Painful crisis was the most common SAE, followed by ACS in the Americas and infections in other regions. VOC rate and percentage of VOC hospitalizations were highest in Europe. Regardless of region, most VOCs were treated with analgesics; approximately half were treated with intravenous fluids. The proportion of VOC-related transfusions was greatest in Europe. Lengths of hospital stay were similar across regions. Conclusions: Overall differences in SAEs and hospitalization for VOCs may be due to cultural diversities, resource utilization, disease severity, or a combination of factors. These data are of importance for the planning of future trials in SCA in a multinational setting.<\/jats:p>","DOI":"10.3390\/jcm8112009","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T04:31:10Z","timestamp":1574051470000},"page":"2009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Geographic Differences in Phenotype and Treatment of Children with Sickle Cell Anemia from the Multinational DOVE Study"],"prefix":"10.3390","volume":"8","author":[{"given":"Baba Psalm Duniya","family":"Inusa","sequence":"first","affiliation":[{"name":"Evelina Children\u2019s Hospital, and Guy\u2019s and St. Thomas\u2019 Hospital, London SE1 7EH, UK"},{"name":"Women and Children\u2019s Health, Faculty of Life Sciences &amp; Medicine, King\u2019s College, London SE1 7EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9797-0457","authenticated-orcid":false,"given":"Raffaella","family":"Colombatti","sequence":"additional","affiliation":[{"name":"Clinic of Pediatric Hematology-Oncology, Azienda Ospedaliera-University of Padua, Padua 35129, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Rees","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology, King\u2019s College London, King\u2019s College Hospital, Denmark Hill, London SE5 8RZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew M.","family":"Heeney","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9213-0547","authenticated-orcid":false,"given":"Carolyn C.","family":"Hoppe","sequence":"additional","affiliation":[{"name":"UCSF Benioff Children\u2019s Hospital Oakland, Oakland, CA 94609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhards","family":"Ogutu","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Research Unit-Kenya, Centre for Clinical Research, Kenya Medical Research Institute, Kisumu 00200, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoda M.","family":"Hassab","sequence":"additional","affiliation":[{"name":"Pediatric Department and Clinical Research Center, Faculty of Medicine, Alexandria University, Alexandria 21500, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunmei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suqin","family":"Yao","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia B.","family":"Brown","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lori E.","family":"Heath","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-4668","authenticated-orcid":false,"given":"Joseph A.","family":"Jakubowski","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel R.","family":"Abboud","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, American University of Beirut, Beirut 11-0236, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0140-6736(12)61229-X","article-title":"Global epidemiology of sickle haemoglobin in neonates: A contemporary geostatistical model-based map and population estimates","volume":"381","author":"Piel","year":"2013","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJM199107043250103","article-title":"Pain in sickle cell disease. 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