{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:00:13Z","timestamp":1792202413644,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R34 HL108756"],"award-info":[{"award-number":["R34 HL108756"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U34 HL148480"],"award-info":[{"award-number":["U34 HL148480"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["U24TR001609"],"award-info":[{"award-number":["U24TR001609"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["U24TR004440"],"award-info":[{"award-number":["U24TR004440"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR003098"],"award-info":[{"award-number":["UL1 TR003098"]}],"id":[{"id":"10.13039\/100006108","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":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high\u2010quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double\u2010blind, phase II feasibility\/pilot trial of dose\u2010escalated hydroxyurea vs. placebo for the primary prevention of CNS injury in children with HbSS or HbS\u2010\u03b2<jats:sup>0<\/jats:sup>\u2010thalassemia subtypes of SCD age 12\u201348\u2009months with normal neurological examination, MRI of the brain, and cerebral blood flow velocity. We hypothesized that hydroxyurea would reduce by 50% the incidence of CNS injury. Two outcomes were compared: primary\u2014a composite of silent cerebral infarction, elevated cerebral blood flow velocity, transient ischemic attack, or stroke; secondary\u2014a weighted score estimating the risk of suffering the consequences of stroke (the Stroke Consequences Risk Score\u2014SCRS), based on the same outcome events. Six participants were randomized to each group. One participant in the hydroxyurea group had a primary outcome vs. four in the placebo group (incidence rate ratio [90% CI] 0.216 [0.009, 1.66], <jats:italic>p<\/jats:italic>\u2009=\u2009.2914) (~80% reduction in the hydroxyurea group). The mean SCRS score was 0.078 (SD 0.174) in the hydroxyurea group, 0.312 (SD 0.174) in the placebo group, <jats:italic>p<\/jats:italic>\u2009=\u2009.072, below the <jats:italic>p<\/jats:italic>\u2010value of .10 often used to justify subsequent phase III investigations. Serious adverse events related to study procedures occurred in 3\/41 MRIs performed, all related to sedation. These results suggest that hydroxyurea may have profound neuroprotective effect in children with SCD and support a definitive phase III study to encourage the early use of hydroxyurea in all infants with SCD.<\/jats:p>","DOI":"10.1002\/ajh.27423","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T07:16:57Z","timestamp":1719904617000},"page":"1906-1916","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hydroxyurea to prevent brain injury in children with sickle cell disease (<scp>HU<\/scp> Prevent)\u2014A randomized, placebo\u2010controlled phase <scp>II<\/scp> feasibility\/pilot study"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2846-9420","authenticated-orcid":false,"given":"James F.","family":"Casella","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Hematology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana K.","family":"Furstenau","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Hematology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J.","family":"Brambilla","sequence":"additional","affiliation":[{"name":"Research Triangle Institute (RTI) International  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Lebensburger","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\u2010Oncology, Department of Pediatrics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Fehr","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7240-0415","authenticated-orcid":false,"given":"Lori C.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison A.","family":"King","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Washington University and St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca N.","family":"Ichord","sequence":"additional","affiliation":[{"name":"Department of Neurology and Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"McKinstry","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Kraut","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Science The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Radiology Seattle Children's Hospital  Seattle Washington 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