{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:06:47Z","timestamp":1791932807540,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Transcranial Doppler ultrasound (TCD) screening for primary stroke prevention in children with sickle cell anemia (SCA) was established in higher\u2010resource regions, targeting interventions for highest velocity (\u201cabnormal\u201d). We sought to identify additional stroke risk factors in Uganda.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a 30\u2010month open\u2010label single\u2010arm Ugandan hydroxyurea trial, dose\u2010escalated to maximum\u2010tolerated dose, aimed to test brain protection for children aged 3\u20139 years with SCA. Study procedures included history, clinical stroke examination, and prospective TCD and laboratory assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 264 children received study HU, mean age 5.6 \u00b1 1.7, hemoglobin 7.8 \u00b1 1.2\u00a0g\/dL, fetal hemoglobin (HbF) 11.9% \u00b1 8.1%, enrolment TCD mean TAMV 148.4 \u00b1 29.3\u00a0cm\/sec; 15 (5.7%) had abnormal TCD. The mean TAMV at trial completion was 131.9 \u00b1 SD 25.7\u00a0cm\/sec. Four participants without abnormal enrolment TCD developed acute stroke within the initial 16 months (incidence 0.62 per 100 person\u2010years): two had enrolment HbF \u22643.1%, two had low oxygen saturation (90%), and one had recurring severe anemia necessitating multiple transfusions. Apparent stroke precipitants were severe malaria, acute chest syndrome, recent pain crisis, or uncertain cause. At trial completion, eight additional participants had a higher risk TCD category than at enrolment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The effectiveness of TCD screening for stroke prevention may vary by region, as no participant with an incident stroke was at the highest risk. Antecedent and\/or ongoing SCA\u2010related risks of anemia, low HbF, hypoxemia, infections, and\/or disease complications likely contributed to stroke despite trial HU. Results suggest that TCD alone may not fully identify the highest stroke risk in the region, and there is a need for primary stroke prevention from early childhood and continuous hydroxyurea therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.31722","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T07:20:27Z","timestamp":1745306427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Incident Stroke in Pediatric Sickle Cell Anemia Despite Overall Improved Transcranial Doppler Velocity in a Ugandan Hydroxyurea Trial: Antecedent and Ongoing Risks"],"prefix":"10.1002","volume":"72","author":[{"given":"Bill","family":"Wambaka","sequence":"first","affiliation":[{"name":"Global Health Uganda  Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amiirah","family":"Mpungu","sequence":"additional","affiliation":[{"name":"Global Health Uganda  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