• Each year, more than 230,000 children with sickle cell disease (SCD) are born in sub-Saharan Africa, compared to 2,600 in North America and 1,300 in Europe. Yet, the natural history of SCD in sub-Saharan Africa remains largely unknown.
• SCD associates episodes of acute illness (acute vaso-occlusive events) and progressive multi-organ damages, which encompass many macro- or microvascular events, such as stroke, heart failure, pulmonary hypertension, kidney disease, bone infarcts, leg ulcers, priapism etc.
• The high inter-individual variability of SCD clinical manifestations is notorious, including in patients with similar genotypes. The reasons of this variability are poorly understood, although clearly both genetic and environmental factors are involved.
• Although the sub Saharan African population is the most afflicted by SCD in the world, most clinical studies concerning SCD chronic complications involve patients from developed countries, where the socio-economic, environmental and medical contexts are dramatically different.

Patients and methods: -Recruitment in hematology and pediatric centers of the capital cities of Cameroon, Mali, Senegal, Ivory Coast and Gabon (replaced by Democratic Republic of Congo in 2016). -Inclusion criteria SCD patients >= 3 years-old (SCD confirmed by hemoglobin electrophoresis and HPLC) investigated at a steady state (no recent vaso-occlusive crisis, infection or transfusion) + age and country matched controls (1 control for 4 patients). -Monitoring of clinical, biological and functional data every five years. Studied complications: - clinically defined : priapism, leg ulcers, stroke, osteonecrosis (confirmed by radio), retinopathy - biologically defined : nephropathy (serum creatinin: eGFR, urine albumin/créatinine ratio) - echocardiography : tricuspid regurgitation jet velocity >2,5m/s (screening for pulmonary hypertension) Abstract source

Quality of care (QOC) has been anecdotally reported as poor overall for sickle cell disease (SCD), especially in the Emergency Department (ED), and poorer for adults versus adolescents. We measured overall, ED, and ambulatory QOC ratings using the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) QOC measures. We compared patients’ overall QOC rating to national Medicare and adult Medicaid population norms. We compared ambulatory to ED QOC, and compared care in adult oriented settings versus pediatric oriented settings. Methods: All patients (N=186, 55% female) were age 15 or older and enrolled in the Start Healing in Patients with Hydroxyurea (SHIP-HU) clinical trial, which required them to see a SCD specialist. Patients were either adolescents and adults in 3 adult clinic sites (A-Cl), or adolescents seen in 3 pediatric clinic sites (P-Cl). At baseline, patients rated overall QOC (0-10), and several items of QOC (1-4 or 1-5, anchored with descriptors: 4 or 5= most positive) as part of ASCQ-Me. Results: At baseline, 80.6% of SHIP-HU enrollees were on HU. In the past 12 months, 91.7% of patients had a usual care doctor or nurse; 95.2% said their usual provider treated a lot of SCD. Satisfaction with ED visits was less than satisfaction with ambulatory visits for all enrollees (mean 3.02 vs. 3.68, p<0.0001), for A-Cl, where the ED ratings were the lowest of all ratings reported (2.93 vs. 3.62, p<0.0001), and for P-Cl, though this difference was not significant (3.42 vs. 3.88, p=0.0781). Overall QOC ratings indicated the worst care (0-6) for 20.2% of patients vs 21% of 2010 adult Medicaid, and 15% of 2010 Medicare national populations. Table 1 shows comparisons between A-Cl and P-Cl. Abstract source

Hydroxycarbamide (hydroxyurea or HU) is an orphan medicinal product for the prevention of recurrent vaso-occlusive crises and acute chest syndrome in adults (US and Europe) and children older than 2 years (Europe) with sickle-cell disease (SCD). HU is generally well tolerated; however, it could have adverse effects on male fertility. Despite the fact that male fertility issues such as delayed puberty, sperm abnormalities and low testosterone level could be directly linked to the underlying SCD, thorough patient information and if it is possible, cryopreservation are recommended before starting HU. It has been demonstrated in a prospective comparison of sperm parameters in SCD adult patients before and after a 6 months treatment with hydroxyurea, impairment in sperm parameters (Bachir et al, 2012). ESCORT-HU (European Sickle Cell Disease Cohort–Hydroxyurea) is a European multicenter, prospective, non-interventional study initiated in Europe to collect more information about the safety profile and morbidity-mortality in SCD patients treated with Siklos® (HU). Our purpose in the present study was to verify whether recommendations regarding male fertility are really implemented and if cryopreservation is a common process in Europe through the preliminary results of ESCORT-HU study. Methods and patients: The data used were from ESCORT-HU study. The cut-off date of data extraction was set as June 19th, 2017. Between January 2009 to June 2017, 1841 patients were enrolled from 63 centers in France, Germany, Greece and Italy. For this analysis only data (age, cryopreservation, sperm analysis results) from male patient were analyzed, no male patient has been excluded. 824 male-patients were aged 0.7 to 78 years at the time of study initiation among which 422 had reached puberty (>15 years of age), with a mean age of 31 years. The main hemoglobin genotype was SS (336 patients), followed by Sß+ (28 patients) and Sß0 (31 patients). Results: On the 422 patients aged 15 years and older, 170 cryopreservations (169 patients) have been reported, among them 121 semen analyses have been recorded. The mean age for performing these examinations was 30 years. Cryopreservations realized systematically with a sperm analysis were mainly performed in France, in contrary to Germany where only children were enrolled and moreover cryopreservations were not supported (Table 1). Before initiation of a treatment with HU, 67 sperms analysis (66 patients) were performed and 50 results (49 patients) were reported. Among them, 33 results (49%) were considered normal and 17 (25%) with abnormalities (at least 1 abnormal criterion: sperm mobility, sperm count, appearance). During HU treatment, 24 sperms analyses (24 patients) were performed and a result was reported for 18 of them. The rate of abnormalities during HU treatment increased to 50% (12 abnormal sperms analysis). Reported abnormalities were asthenospermia, hypospermia, oligospermia, azoospermia and atypical forms (Table 2). Abstract source

Measurement of access to care and utilization for adults with sickle cell disease (SCD) compared to children has been primarily through analysis of administrative databases. We report here the first comparative results of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) access and utilization measures for adolescents vs. adults. Methods: Patients (N=186, 55% female) ages 15 and older were enrolled in the Start Healing in Patients with Hydroxyurea (SHIP-HU) clinical trial, which required them to see a SCD specialist. Patients were either seen in 3 adult-oriented clinic sites, or seen in 3 pediatric-oriented clinic sites. At baseline, ASCQ-Me queried care seeking and numbers of visits for both ambulatory and Emergency Department (ED) care. Results: Fully 92% had a usual care doctor or nurse, their SCD provider, whom they saw on average 3.3 times in the previous 12 months (p=0.7074, patients seen in adult-oriented clinics [A-Cl] vs. patients seen in pediatric-oriented clinics [P-Cl]).^ At baseline, 77.7% of A-Cl and 89.4% of P-Cl were on HU (p=0.0769). In the past 12 months, 87% of A-Cl vs. 73% of P-Cl had tried to make an appointment to see a doctor or nurse (p=0.0321). Compared to all other responses (never, sometimes, usually), only 36% of A-Cl vs. 49% of P-Cl said they could always get an appointment soon enough (p=0.1967). A total of 64/135 A-Cl (47%) vs. 10/47 P-Cl (21%) reported no crises in the preceding 12 months (p=0.0017). Among those reporting home-managed crises without medical contact, the mean number was 2.0 for A-Cl vs 2.7 for P-Cl (p=0.0241). ^ Fully 66% of A-Cl vs. 43% of P-Cl at some point delayed/ avoided ED care for crises (p=0.0039). Reasons for avoiding ED care included prior bad experiences (very, quite, or somewhat important for 63% of A-Cl vs. 45% of P-Cl, p=0.1458) and health insurance issues (very, quite, or somewhat important for 30% of A-Cl vs. 40% of P-Cl, p=0.3680). Still, 76% of A-Cl vs 54% of P-Cl reported ED visits for crises (p=0.0043). The mean number of ED visits was 2.2 for A-Cl vs. 1.2 for P-Cl (p=0.0003).^ Compared to all other responses (never, sometimes, usually), only 19% of A-Cl vs. 38% of P-Cl said they could always get ED care as soon as they wanted (p=0.0540)--49% of A-Cl vs. 16% of P-Cl had to wait more than an hour to be medicated in the ED (p=0.0031; 32% of A-Cl vs 8% of P-Cl had to wait more than 2 hours (p=0.0156). Abstract source

Acute chest syndrome (ACS) is the second most common cause of admission and the main cause of death in patients with sickle cell disease (SCD). Nearly half of ACS cases develop during hospitalizations. Incentive spirometry (IS) use decreases the incidence of ACS during hospitalization. The 2014 NHLBI guidelines for the management of SCD encouraged the use of incentive spirometry in hospitalized patients to prevent the development of ACS (strong recommendation, moderate-quality evidence). Despite the available evidence and recommendations, IS is underutilized and the use of this simple, inexpensive, and effective intervention in hospitalized patients with SCD is inconsistent. We sought to develop and implement a standardized process to ensure a reliable use of IS in hospitalized patients with SCD and measure its effect on the occurrence of ACS. Methods: Based on the model for improvement, we implemented a standard process that involved several interventions to improve the use of IS in all hospitalized children and young adults with SCD at Cincinnati Children’s Hospital Medical Center. Interventions included the development of an electronic medical record-based order set to standardize IS orders, supplying inpatient units with incentive spirometers for timely delivery, increasing awareness through education of staff, patients and families, discussing IS use during daily rounds, and standardization of the nursing documentation of IS use. The primary outcome was the percent ACS diagnosis per inpatient encounters per month. Results: We analyzed all SCD inpatient encounters one year before (April 2015-April 2016; n=224) and one year after (May 2016-May 2017; n=214) the implementation of the new process. The frequency of ACS diagnosis was reduced from 22% (50/224) pre-intervention to 12% (25/214) post-intervention (P=0.002). The median rate of ACS diagnosis per month was reduced from 23% to 12% and this reduction was maintained over one year post intervention. There was an improvement in the reliability of all measurable key processes targeted during this initiative. The percent of inpatient encounters with accurate IS orders increased from 28% to 88% and the percent of encounters with documented actual IS use by the patient improved from 41% pre-intervention to 81% post-intervention. There also was a trend of decreased length of stay from an average of 3.3 days in the 12 months preceding intervention to an average of 3.1 days in the year following the implementation of the new process. Possibly due to increased awareness for ACS among the clinical staff, there also was an unintended increase in the number of chest radiographs (CXR) performed from 16% pre-intervention (35 total CXR) to 37% post- intervention (70 total CXR). Despite this increase in the number of CXR performed, the diagnosis of ACS was still decreased by nearly half. Abstract source

In the 52-week SUSTAIN study, which compared the P-selectin inhibitor crizanlizumab with placebo, crizanlizumab 5.0 mg/kg significantly reduced the frequency of sickle cell pain crises (SCPCs) versus placebo (1.6 vs 3.0, P=0.01) and increased the time to first on-treatment SCPC (4.1 vs 1.4 months, P=0.001) in patients with sickle cell disease (SCD) (Ataga KI et al. N Engl J Med 2017;376:429–39). Due to heterogeneity in disease severity and differences in medications used for the treatment of SCD and various other factors, treatment responses may vary between individuals with SCD. Differences in the response to crizanlizumab observed in defined subgroups of patients are of interest to increase understanding of this treatment, and the role of P-selectin in SCD. Aims: This post hoc analysis evaluated the time to first SCPC in subgroups of the SUSTAIN study population to further assess the efficacy of crizanlizumab 5.0 mg/kg and differences in treatment response between those subgroups. Methods: SUSTAIN was a randomized, double-blind, placebo-controlled, Phase II study (NCT01895361). Patients aged 16–65 years with SCD (HbSS, HbSC, HbSβ0–thalassemia, HbSβ+–thalassemia or other genotype) were included if they had experienced 2–10 SCPC events in the previous 12 months. Concomitant use of hydroxyurea (HU) was permitted if the patient had been using it for ≥6 months and at a stable dose for ≥3 months. Patients were randomized 1:1:1 to receive intravenous crizanlizumab 5.0 mg/kg, 2.5 mg/kg or placebo; however, this abstract focuses on the 5.0 mg/kg dose of crizanlizumab versus placebo. Study treatments were administered on days 1 and 15, then every 4 weeks to week 50; the final study visit of the treatment phase was at week 52, with an additional follow-up visit at week 56. The median time to first SCPC after the first dose of study treatment was summarized for patients treated with crizanlizumab 5.0 mg/kg or placebo in the following subgroups: 2–4 or 5–10 SCPC events in the previous 12 months; HbSS or non-HbSS genotype; and HU use (yes or no) at baseline. Hazard ratios (HRs) for crizanlizumab 5.0 mg/kg versus placebo were calculated based on Cox regression analysis, with treatment as a covariate. Results: 67 patients in the intent-to-treat population received crizanlizumab 5.0 mg/kg and 65 received placebo. Overall, more patients who had experienced 2–4 SCPCs (63% in both groups) than 5–10 SCPCs (37% in both groups) in the previous year were enrolled. HbSS was the most common genotype (crizanlizumab 5.0 mg/kg: 70%; placebo: 72%), and more than half of patients were taking HU at baseline (crizanlizumab 5.0 mg/kg: 63%; placebo: 62%). In almost all the subpopulations evaluated, crizanlizumab 5.0 mg/kg significantly (P<0.05) increased the time to first SCPC versus placebo by two-fold or greater (Table). The effect was present in both SCPC subgroups (2–4 and 5–10 SCPCs in the previous year). The largest treatment difference was observed in patients with the HbSS genotype, with a 3.7-fold increase in time to first SCPC observed for crizanlizumab 5.0 mg/kg versus placebo (4.1 vs 1.1 months; HR: 0.50). It is also notable that in patients taking HU who experienced 2–10 SCPCs in the previous year, the time to first on-study SCPC was longer with crizanlizumab 5.0 mg/kg versus placebo (2.4 vs 1.2 months; HR: 0.58). Abstract source

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States (US). Affected individuals suffer from multiple complications due to deoxygenation-induced polymerization of hemoglobin S in red blood cells. Injury from SCD starts at birth and accumulates over time causing significant end-organ damage and ischemic tissue injury, leading to fatigue, pain (vaso-occlusive crisis [VOC]), and other clinical complications. For many patients, SCD related pain exists at a nearly constant baseline of low-to-moderate intensity while exacerbations to severe intensity occur unpredictably. Per clinical guidelines, opioids are recommended for treatment of acute pain episodes (i.e. VOC) as well chronic pain that cannot be otherwise managed, and many SCD patients require long-term opioid therapy to achieve adequate pain relief. Given limited real world data on current opioid treatment patterns among SCD patients, this study was undertaken to describe opioid utilization patterns in a large cohort of SCD patients in the US. Methods: The Truven MarketScan® Commercial and Medicaid administrative claims databases were used to identify patients with SCD (1 inpatient or 2 outpatient claims with ICD-9 282.6x, 282.41, and/or 282.42) recorded in each calendar year from 2009 to 2014; 1 cohort was constructed for each year, and patients may have been diagnosed previously. Patients aged >=9 months at the first indication of SCD were included. In each cohort, patients were required to be enrolled in medical and pharmacy benefits for the calendar year in which they were identified. The final cohorts were restricted to patients with 12 months continuous medical and pharmacy benefits coverage prior to their first SCD indication in the cohort year. Prior year utilization of opioids and morphine equivalent daily dose (MEDD) was measured for each cohort using outpatient pharmacy claims. MEDD was defined as the daily dose multiplied by a drug-specific morphine conversion factor, and was calculated among the subset of opiates with a known conversion factor, and reported as the mean of a patient’s average MEDD over the year prior to their first indication of SCD in the cohort year. VOCs were identified by ICD-9 codes 282.42, 282.62, 282.64, and 282.69 in the year prior to the cohort year. Results are reported as ranges across the annual cohorts and stratified by payer (Commercial or Medicaid) and age group (<6, 6-11, 12-17, 18-30, 31-44, 45+). Results: There were 2,619-3,285 Commercial and 4,807-7,007 Medicaid SCD patients identified in each of the annual cohorts. The mean age was 27 in Commercial cohorts and >50% were female. The mean age was 18 in the Medicaid cohorts and about 50% were female. The proportion of SCD patients prescribed opioids remained stable each year across the study period, with consistently more Medicaid patients using an opioid (65%-70%) compared to Commercial patients (54%-57%) [Table]. Medicaid patients had more opioid days supplied and opioid claims per patient across all age groups. Among both payers, opioid claims and days supplied were consistent over time (Table). SCD patients had markedly higher use of opioids in the prior year compared to the 30 day prior use in the general US population, but all remained steady over time. The proportions of patients with a VOC and patients using opioids increased markedly between age 12-17 and 18-30 in Medicaid and Commercial patients. MEDD and average days supplied per patient also increased substantially between age 12-17 to age 18-30 in both payers (Table), which coincided with the transition from pediatric to adult care. Medicaid patients reached a utilization level of >=4 months supply of opioids earlier (age 18-30) than Commercial patients (age 31-44) and had double the average days supplied in each adult (age >=18 years old) age group. Abstract source

Sickle cell disease (SCD)-related mortality is a significant cause of mortality among Blacks in the United States. Several clinical interventions, such as penicillin prophylaxis, vaccination, and hydroxyurea, have decreased SCD-related mortality over time. This report investigates changes in the causes of death (COD) associated with SCD-related mortality over time and among age groups and compares SCD-related deaths to non-SCD-related deaths to identify changes in the burden of specific COD in order to inform future public health improvement efforts. Methods: SCD-related deaths were examined using the 1979-2014 US multiple COD mortality data. SCD-related deaths were identified as deaths for which an International Classification of Disease 9th revision (ICD-9) or ICD-10 code for SCD (282.6 for ICD-9; D57.0, D57.1, D57.2, D57.8 for ICD-10) was listed anywhere on the death record. Age-specific annual and average annual SCD-related death rates were calculated as the number of deaths per 100,000 corresponding population, with the bridged-race intercensal estimates of the US resident population as the denominator. Because death from SCD is a rare event in races other than Black, the analysis focused on decedents of Black race. Underlying and contributing COD codes were categorized according to their ICD-9 or ICD-10 codes into 20 groups relevant to SCD outcomes, including acute infection complications, cerebrovascular complications, splenic complications, and renal complications. To compare SCD-related deaths to non-SCD deaths, death records not listing an ICD-9 or ICD-10 code for SCD were randomly selected in a 1:1 ratio; non-SCD deaths were matched to SCD deaths by race, sex, age group, year of death, and region of residence. Results: From 1979-2014 there were 23,226 SCD-related deaths reported in the US. The median age at death increased from 28 years in 1979 to 43 years in 2014. The SCD-related average annual death rate trends shifted by time period across various age groups. The average annual SCD-related death rate among children <5 years of age declined from 2.05/100,000 in 1979-1989 to 0.35/100,000 in 2011-2014 (p<.0001). Conversely, the rate among adults ≥60 years of age increased from 1.20/100,000 in 1979-1989 to 1.69/100,000 in 2000-2014 (p<0.0001). Changes in the frequency of various underlying and contributing COD among SCD-related deaths reflects the success of clinical interventions. During the first time period (1979-1989) acute cardiac and infection complications were the most common underlying and contributing COD. In contrast, chronic cardiac complications was most commonly listed as the underlying or contributing COD during the last time period (2010-2014). The underlying and contributing COD listed among SCD-related deaths also differed by age group. The most common COD among deaths occurring at <5 years of age was acute infection. The most common COD among deaths occurring at ≥60 years of age was cardiac complications. While clinical interventions have shown effect, compared to non-SCD-related deaths, SCD-related deaths remained more likely to be related to COD, such as acute infections, cerebrovascular complications, and renal complications. Abstract source

Introduction: Survivorship of children with sickle cell disease (SCD) has substantially increased due to the advent of medical advances, such as sepsis prevention (prophylactic penicillin) and exposure to disease-modifying therapies (chronic transfusion and hydroxyurea). Despite greater longevity in SCD, the period surrounding the transition from pediatric to adult care has the highest prevalence of undesirable outcomes: youth aged 18-30 years are at high risk for mortality and high rates of healthcare utilization, resulting in increased healthcare costs. As such, health care transition programs have been created to prepare patients with SCD for adult-centered care and subsequently, improve health outcomes. However, few programs have been evaluated for effectiveness in achieving optimal health outcomes in SCD in part because of a lack of identifiable predictors and outcomes. Objective: To identify factors necessary for successful health care transition, as judged by pediatric and adult healthcare professionals involved with the SCD population. Method: Individuals who provide clinical care for or conduct clinical research with patients with SCD were eligible to participate in the survey and were collectively defined as providers. Providers were recruited online through nationally recognized professional societies, SCD provider contact lists and in person at a national SCD conference. Links to an online survey, administered via Qualtrics software, were distributed to potential participants. The survey included demographic questions and a list of 36 transition factors, including disease knowledge, self-management behaviors, and independent living skills. Participants were asked to rate the level of importance of each factor in helping a patient with SCD successfully transition from pediatric to adult care on a scale from 1 (not important) to 10 (very important). They were then asked to select five of the 36 factors they believed were most necessary for a successful transition, ranking them from 1 (highest) to 5 (lowest). Descriptive statistics were conducted to determine the top ratings and rankings. A two-way MANOVA was conducted to examine whether the top ratings were different according to provider gender and occupation. Results: The sample included 258 providers (74% female, 65% White). The majority were hematologists (41%); 38% were other medical staff (e.g., nurse, midlevel providers, other physicians) and 21% were non-medical staff (e.g., psychologist, social worker, researchers). The transition factor ratings (scale 1 to 10) ranged from 5.82-9.62 (M=8.05, SD=1.74). The factors with the highest ratings included: Knows how to take medications (M=9.62, SD=0.82), Explains/communicates medical needs to medical personnel (M=9.50, SD=0.93), Knows when to seek medical assistance if home management fails (M=9.32, SD=1.12), and Knows how to manage pain episodes (M=9.31, SD=1.18). These same four factors also were ranked as the top five most relevant factors: Knows how to manage pain episodes (N=138, 53%, M=2.59, SD=1.30), Explains/communicates medical needs to medical personnel (N=115, 45%, M=2.54, SD=1.38), Knows how to take medications (N=135, 52%, M=2.67, SD=1.31), Knows when to seek medical assistance if home management fails (N=102, 40%, M=2.97, SD=1.46). Knows medical history (N=100, 39%, M=2.57, SD=1.35) was the fifth most relevant factor. Multivariate results indicated a trend toward hematologists giving lower ratings compared to other medical and non-medical professionals, F (8, 486) = 1.91, p = .057. Abstract source

Sickle cell anemia is associated with progressive compromise of neurocognitive function exacerbated by stroke or silent cerebral infarction. Despite decades of experience with chronic transfusion, hematopoietic stem cell transplantation, and HU, improvement in neurocognitive performance from these interventions has not been clearly demonstrated; only one study has reported improvement in global cognitive index from HU (Puffer, Child Neuropsychology, 2007). As part of a comprehensive prospective evaluation of the effects of HU treatment on the central nervous system, we evaluated neuropsychological performance in school-age children with sickle cell anemia. Methods: Subjects had HbSS/Sβ0 thalassemia and no history of previous central nervous system (CNS) events and were 7-18 years old. After informed consent, baseline evaluations included the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV) and the Woodcock-Johnson Achievement Test Version III (WJ-III). Treated patients received HU beginning at 20 mg/kg/d with gradual escalation to maximum tolerated dose (MTD) within one year. They were evaluated with the same CNS studies after 12 months. A control group who declined HU treatment was matched by diagnosis and age and was also evaluated at baseline and after one year. Summary statistics of WISC and WJ-III scores were reported for each time point and for their change between two time points in each group and were compared using the Wilcoxon rank sum and Wilcoxon signed rank tests, respectively. Results: Age and gender distributions in HU-treated (n=21) and untreated control patients (n=11) were comparable. In HU-treated patients, but not in controls, there was significant improvement in mean full scale IQ (FSIQ) after one year (Table 1). In treated subjects, mean WISC subscale scores were all higher after one year, although none were statistically significant. Among controls, FSIQ and all subscales, except working memory, showed a numerical decrease in mean scores, with the greatest decline in perceptual reasoning. Subtest scores from the WJ-III Achievement test in HU-treated patients showed significant improvement in comprehension of word passages. Among controls, WJ-III Achievement subtest scores showed no significant changes. When mean changes in WISC scores from baseline to one-year follow-up were compared (Table 2), treated patients showed greater positive changes than controls, but differences were not significant. Changes in WJ-III scores for treated and control subjects also were not significant. Conclusions: In children with sickle cell anemia, HU treatment over a one year period was associated with a significant improvement in the Wechsler Full Scale IQ; subscales showed small to medium positive changes although the differences were not statistically significant. By contrast, in the untreated control group, most scores were lower after one year and mean changes in scores from baseline were less positive than those in the HU group. In measures of achievement, the treated group demonstrated improved passage (reading) comprehension, a skill related to executive function. Overall, these results suggest that HU may improve cognitive function or prevent decline. Correlation of standard and functional MR neuroimaging in these subjects with neurocognitive performance is pending. Future trials are needed to examine the impact of other interventions (e.g., memory training, multisensory reading intervention), possibly in conjunction with HU. Abstract source