Approximately 40 000 children with sickle cell anemia require screening with TCD and treating with hydroxyurea for stroke prevention in three states in northern Nigeria.
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SUBMITTER: Galadanci AA
PROVIDER: S-EPMC7520898 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
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Approximately 40 000 children with sickle cell anemia require screening with TCD and treating with hydroxyurea for stroke prevention in three states in northern Nigeria.
Galadanci Aisha A AA Galadanci Najibah A NA Jibir Binta W BW Abdullahi Shehu U SU Idris Nura N Gambo Safiya S Ali Abubakar Shehi A SA Kabo Nasiru A NA Bello-Manga Halima H Haliru Lawal L Bashir Ibrahim I Aliyu Muktar H MH Galadanci Jamil A JA DeBaun Michael R MR
American journal of hematology 20190911 11
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Project description:IntroductionSickle cell anemia (SCA) is a severe, inherited hemoglobin disorder affecting 100,000 persons in the US and millions worldwide. Hydroxyurea, a once daily oral medication, has emerged as the primary disease-modifying therapy for SCA. The accumulated body of evidence over 30 years demonstrates that hydroxyurea is a safe and effective therapy for SCA, but hydroxyurea remains underutilized for a variety of reasons.Areas coveredIn this review, we summarize the available evidence regarding the pharmacology, clinical, and laboratory benefits, and safety of hydroxyurea therapy for the treatment of SCA. The purpose of this review is to provide the reader a comprehensive understanding of hydroxyurea and to reinforce the fact that hydroxyurea is a safe and effective medication for the treatment of SCA.Expert opinionIn our opinion, hydroxyurea therapy should be considered standard-of-care for SCA, representing an essential component of patient management. Early initiation and broader use of hydroxyurea will alter the natural history of SCA, so affected children can live longer and healthier lives. In addition, hydroxyurea use should be extended to low-resource settings such as sub-Saharan Africa, where the burden of SCA and the need for hydroxyurea is arguably the greatest.
| S-EPMC5868345 | biostudies-literature
Project description: Not available
| S-EPMC6235722 | biostudies-literature
Project description:We tested the hypothesis that fixed oral moderate-dose hydroxyurea (20 mg/kg per day) for initial treatment of secondary stroke prevention results in an 80% relative risk reduction of stroke or death when compared with fixed oral low-dose hydroxyurea (10 mg/kg per day) in a phase 3 double-blind, parallel-group, randomized controlled trial in children with sickle cell anemia (SCA) living in Nigeria. A total of 101 participants were randomly allocated to low-dose (n = 49) and moderate-dose (n = 52) hydroxyurea treatment groups. The median participant follow-up was 1.6 years (interquartile range, 1.0-2.3), with a planned minimum follow-up of 3.0 years. A total of 6 recurrent strokes and 2 deaths vs 5 recurrent strokes and 3 deaths occurred in the low- and moderate-dose groups, respectively. The incidence rate ratio (IRR) of the primary outcome measure of stroke or death in the low- and moderate-dose hydroxyurea treatment groups was 0.98 (95% confidence interval [CI], 0.32-3.00; P = .97). The trial was stopped early owing to no clinical difference in the incidence rates of the primary outcome measure. The incidence rates of recurrent strokes were 7.1 and 6.0 per 100 person-years in the low- and moderate-dose groups, respectively, (IRR, 1.18; 95% CI, 0.30-4.88; P = .74). As a measure of adherence to the oral hydroxyurea therapy, the median percent of returned pills was 3.0% and 2.6% in the low- and moderate-dose groups, respectively. No participant had hydroxyurea therapy stopped for myelosuppression. For children with SCA in low-income settings without access to regular blood transfusion therapy, initial low-dose hydroxyurea is a minimum known efficacious dose for secondary stroke prevention.
| S-EPMC10023719 | biostudies-literature
Project description:Background and objectiveSusceptibility to encapsulated bacteria is well known in sickle cell disease (SCD). Hydroxyurea use is common in adults and children with SCD, but little is known about hydroxyurea's effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1-S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses.MethodsT-cell subsets, naive and memory T cells, and antibody responses to pneumococcal and measles, mumps, and rubella vaccines were measured among participants in a multicenter, randomized, double-blind, placebo-controlled trial of hydroxyurea in infants and young children with SCD (BABY HUG).ResultsCompared with placebo, hydroxyurea treatment resulted in significantly lower total lymphocyte, CD4, and memory T-cell counts; however, these numbers were still within the range of historical healthy controls. Antibody responses to pneumococcal vaccination were not affected, but a delay in achieving protective measles antibody levels occurred in the hydroxyurea group. Antibody levels to measles, mumps, and rubella showed no differences between groups at exit, indicating that effective immunization can be achieved despite hydroxyurea use.ConclusionsHydroxyurea does not appear to have significant deleterious effects on the immune function of infants and children with SCD. Additional assessments of lymphocyte parameters of hydroxyurea-treated children may be warranted. No changes in current immunization schedules are recommended; however, for endemic disease or epidemics, adherence to accelerated immunization schedules for the measles, mumps, and rubella vaccine should be reinforced.
| S-EPMC4179098 | biostudies-literature
Project description:BackgroundThe Multicenter Study of Hydroxyurea (HU) in Sickle Cell Anemia (MSH) previously showed that daily oral HU reduces painful sickle cell (SS) crises by 50% in patients with moderate to severe disease. The morbidity associated with this disease is known to have serious negative impact on the overall quality of life(QOL) of affected individuals.MethodsThe data in this report were collected from the 299 patients enrolled in the MSH. Health quality of llife (HQOL) measures were assessed in the MSH as a secondary endpoint to determine if the clinical benefit of HU could translate into a measurable benefit perceptible to the patients. HQOL was assessed with the Profile of Mood States, the Health Status Short Form 36 (SF-36), including 4-week pain recall, and the Ladder of Life, self-administered twice 2-weeks apart pre-treatment and every 6 months during the two-year, randomized, double-blind, treatment phase. The effects of factors including randomized treatment, age, gender, pre-treatment crises frequency, Hb-F level mean, daily pain from 4-week pre-treatment diaries, and 2-year Hb-F response level (low or high) were investigated.ResultsOver two years of treatment, the benefit of HU treatment on QOL, other than pain scales, was limited to those patients taking HU who maintained a high HbF response, compared to those with low HbF response or on placebo. These restricted benefits occurred in social function, pain recall and general health perception. Stratification according to average daily pain prior to treatment showed that responders to HU whose average daily pain score was 5-9 (substantial pain) achieved significant reduction in the tension scale compared to the placebo group and to non-responders. HU had no apparent effect on other QOL measures.ConclusionTreatment of SS with HU improves some aspects of QOL in adult patients who already suffer from moderate-to-severe SS.
| S-EPMC1569824 | biostudies-literature
Project description:Background: Despite a high incidence of sickle cell anemia, hydroxyurea (HU) treatment is rarely used in the DR Congo. This study aims to assess the efficacy of HU, the incidence of side effects that may limit its use in adults and to determine the dose needed for clinical improvement in patients. Methods: In a prospective study, patients received an initial dose of 15 mg/kg/day which was increased by 5 mg/kg every 6 months, up to a maximum of 30 mg/kg/day. The response and side effects to HU were evaluated biologically and clinically every 3 months during a 2-year period. Results: Seventy adult patients with a moderate or severe clinical phenotype initiated treatment. Only minor side effects were reported. At the end of the 2-year treatment phase, 45 (64.3%) had dropped out, of whom 33 were without a clear reason. Clinical and biological improvement was more marked during the first year. There was a reduction in severe vaso-occlusive crises (p < 0.001), need for transfusion (p < 0.001), and hospitalization days (p = 0.038). Fetal hemoglobin (HbF) levels increased on average 2.9 times after 12 months (p < 0.001). The increase in mean corpuscular volume was greater in the first year (p < 0.001) than in the second year (p = 0.041). The decrease in leukocytes (p < 0.001) was significant during the first year. In 70% of patients, the 20 mg/kg/day dose was needed to reach the 20% HbF threshold. Conclusion: HU is effective and well tolerated. The magnitude of the response varies from one patient to another. Improvement of clinical manifestations is achieved in most patients with a relatively low dose. Effective implementation of HU treatment will require improved adherence to treatment.
| S-EPMC10435708 | biostudies-literature
Project description: Not available
| S-EPMC5389903 | biostudies-literature
Project description:BackgroundHydroxyurea is an effective treatment for sickle cell anemia, but few studies have been conducted in sub-Saharan Africa, where the burden is greatest. Coexisting conditions such as malnutrition and malaria may affect the feasibility, safety, and benefits of hydroxyurea in low-resource settings.MethodsWe enrolled children 1 to 10 years of age with sickle cell anemia in four sub-Saharan countries. Children received hydroxyurea at a dose of 15 to 20 mg per kilogram of body weight per day for 6 months, followed by dose escalation. The end points assessed feasibility (enrollment, retention, and adherence), safety (dose levels, toxic effects, and malaria), and benefits (laboratory variables, sickle cell-related events, transfusions, and survival).ResultsA total of 635 children were fully enrolled; 606 children completed screening and began receiving hydroxyurea at a mean (±SD) dose of 17.5±1.8 mg per kilogram per day. The retention rate was 94.2% at 3 years of treatment. Hydroxyurea therapy led to significant increases in both the hemoglobin and fetal hemoglobin levels. Dose-limiting toxic events regarding laboratory variables occurred in 5.1% of the participants, which was below the protocol-specified threshold for safety. During the treatment phase, 20.6 dose-limiting toxic effects per 100 patient-years occurred, as compared with 20.7 events per 100 patient-years before treatment. As compared with the pretreatment period, the rates of clinical adverse events decreased with hydroxyurea use, including rates of vaso-occlusive pain (98.3 vs. 44.6 events per 100 patient-years; incidence rate ratio, 0.45; 95% confidence interval [CI], 0.37 to 0.56), nonmalaria infection (142.5 vs. 90.0 events per 100 patient-years; incidence rate ratio, 0.62; 95% CI, 0.53 to 0.72), malaria (46.9 vs. 22.9 events per 100 patient-years; incidence rate ratio, 0.49; 95% CI, 0.37 to 0.66), transfusion (43.3 vs. 14.2 events per 100 patient-years; incidence rate ratio, 0.33; 95% CI, 0.23 to 0.47), and death (3.6 vs. 1.1 deaths per 100 patient-years; incidence rate ratio, 0.30; 95% CI, 0.10 to 0.88).ConclusionsHydroxyurea treatment was feasible and safe in children with sickle cell anemia living in sub-Saharan Africa. Hydroxyurea use reduced the incidence of vaso-occlusive events, infections, malaria, transfusions, and death, which supports the need for wider access to treatment. (Funded by the National Heart, Lung, and Blood Institute and others; REACH ClinicalTrials.gov number, NCT01966731 .).
| S-EPMC6454575 | biostudies-literature
Project description: Not available
| S-EPMC10685164 | biostudies-literature
Project description:ObjectiveTo evaluate the impact of an initiative to increase hydroxyurea use among children with sickle cell anemia (SCA) who presented to the emergency department (ED).Study designThis observational cohort study included children with SCA not taking hydroxyurea who presented to the ED with pain or acute chest syndrome and then attended a Quick-Start Hydroxyurea Initiation Project (Q-SHIP) session. A Q-SHIP session includes a hematologist-led discussion on hydroxyurea, a video of patients talking about hydroxyurea, and a direct offer to start hydroxyurea.ResultsOver 64 weeks, 112 eligible patients presented to the ED and 59% (n = 66) participated in a Q-SHIP session a median of 6 days (IQR 2, 20 days) after ED or hospital discharge; 55% of participants (n = 36) started hydroxyurea. After a median follow-up of 49 weeks, 83% (n = 30) of these participants continued hydroxyurea. Laboratory markers of hydroxyurea adherence were significantly increased from baseline: median mean corpuscular volume +8.6 fL (IQR 5.0, 17.7, P < .0001) and median hemoglobin F +5.7% (IQR 2.5, 9.8, P = .0001). Comparing Q-SHIP participants to nonparticipants, 12 weeks after ED visit, participants were more likely to have started hydroxyurea than nonparticipants (53% vs 20%, P = .0004) and to be taking hydroxyurea at last follow-up (50% vs 20%, P = .001). Two years after the implementation of Q-SHIP the overall proportion of eligible patients on hydroxyurea presenting to our ED increased from 56% to 80%, P = .0069.ConclusionsParticipation in a clinic to specifically address starting hydroxyurea after a SCA complication increases hydroxyurea use.
| S-EPMC6159227 | biostudies-literature