{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:31:02Z","timestamp":1781850662917,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009210","name":"Food and Drug Administration","doi-asserted-by":"publisher","award":["R01FD006030"],"award-info":[{"award-number":["R01FD006030"]}],"id":[{"id":"10.13039\/100009210","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL159376"],"award-info":[{"award-number":["HL159376"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hydroxyurea reduces the frequency of vaso\u2010occlusive complications, increases hemoglobin, and decreases mortality in sickle cell disease (SCD). Although current guidelines recommend escalation to maximum tolerated dose (MTD), the use of fixed low\u2010dose hydroxyurea is common in low\u2010resource countries. We conducted a systematic review and meta\u2010analysis to evaluate the efficacy of escalated doses versus fixed low\u2010dose of hydroxyurea in adults with SCD. Nine studies were included in the quantitative synthesis, four evaluating fixed low\u2010dose and five evaluating escalated doses of hydroxyurea. Average daily doses of hydroxyurea in the fixed low\u2010dose and escalated dose studies were ~10 and 22\u2009mg\/kg, respectively. There was no difference in the estimate of vaso\u2010occlusive crisis rate between escalated and fixed low\u2010dose studies (<jats:italic>p<\/jats:italic>\u2009=\u2009.73). The mean difference in hemoglobin from baseline to follow\u2010up was greater for fixed low\u2010dose than escalated dose studies (1.07\u2009g\/dL vs. 0.54\u2009g\/dL, <jats:italic>p<\/jats:italic>\u2009=\u2009.01). No difference was seen in the mean estimate of fetal hemoglobin. Despite limited eligible studies and substantial heterogeneity of effect between the studies for several outcomes, there appears to be clinical equipoise regarding the most appropriate hydroxyurea dosing regimen in adults with SCD. Controlled studies of hydroxyurea at MTD versus fixed low\u2010dose in adults with SCD are required.<\/jats:p>","DOI":"10.1111\/ejh.14138","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T14:09:50Z","timestamp":1701266990000},"page":"466-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hydroxyurea at escalated dose versus fixed low\u2010dose hydroxyurea in adults with sickle cell disease"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4662-1414","authenticated-orcid":false,"given":"Ugochi O.","family":"Ogu","sequence":"first","affiliation":[{"name":"Center for Sickle Cell Disease University of Tennessee Health Science Center  Memphis Tennessee USA"},{"name":"Division of Hematology\/Oncology University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3608-0385","authenticated-orcid":false,"given":"Ayesha","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health University of Memphis  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6527-5916","authenticated-orcid":false,"given":"Kruti","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3969-2293","authenticated-orcid":false,"given":"Marquita N.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Center for Sickle Cell Disease University of Tennessee Health Science Center  Memphis Tennessee 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