Research consistently indicates that children with sickle cell disease (SCD) face multiple risk factors for neurocognitive impairment. Despite this, no empirical research to date has examined the impact of neurocognitive functioning on quality of life for this pediatric group. Thus, the current study aims to examine the relationship between executive functioning and quality of life in a sample of children with SCD and further explore psychosocial and family/caregiver resources as moderators of this relationship. A total of 45 children with SCD aged 8 to 16 years and their caregivers completed measures of quality of life, behavioral ratings of executive functioning, and psychosocial functioning. Hierarchical linear regression models were utilized to determine the impact of executive functioning on quality of life and further test the interaction effects of proposed moderating variables. Controlling for age, pain, and socioeconomic status (SES), executive functioning was found to significantly predict child- and parent-reported quality of life among youth with SCD. Psychosocial resources of the primary caregiver or family was not found to moderate the relationship between executive functioning and quality of life. These results provide the first empirical evidence that lower executive skills negatively predict quality of life for children with SCD, supporting clinical and research efforts which aim to establish efficacious interventions that target cognitive decrements within this pediatric population. Abstract source Full text

Sickle cell trait (SCT) is usually benign. However, there are some conditions that may lead to SCT-related problems and put athletes with the trait at particular risk. In 2010 the National Collegiate Athletic Association (NCAA) issued a policy that required all Division I (DI) student-athletes to confirm their SCT status or sign a liability waiver to opt out of testing. Athletic trainers and team physicians play key roles in the policy implementation and we examined their perceptions and practices. Between December 2013 and March 2014 we interviewed 13 head athletic trainers and team physicians at NCAA Division I colleges and universities in North Carolina. We used an interview guide with open-ended questions covering knowledge of SCT, historical screening and education practices, current implementation, and policy benefits and challenges. Participants were knowledgeable about SCT and thought the policy was beneficial in providing SCT health information to and for student-athletes. Schools varied in provision of genetic counseling, offering the waiver, SCT tests administered, and other aspects. Challenges included: insufficient guidance from the NCAA; financial considerations; and misunderstanding of the relationships of race and ancestry to SCT risk. Athletic staff found the policy valuable, but felt it needs clarity and standardization. Abstract source Full text

Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of healthcare utilization. Among 161 patients with a 2-year overall survival rate of 90% (95% confidence interval [CI] 85-95%) mortality was significantly higher in those who underwent late transplantation versus early (hazard ratio (HR) 21, 95% CI 2.8-160.8, P=0.003) and unrelated compared to matched sibling donor transplantation (HR 5.9, 95% CI 1.7-20.2, P=0.005). Chronic graftversus host disease was significantly more frequent among those translanted late (HR 1.9, 95% CI 1.0-3.5, P=0.034) and those who received an unrelated graft (HR 2.5, 95% CI 1.2-5.4; P=0.017). Merged data for 176 patients showed that the median total adjusted transplant cost per patient was $467,747 (range: $344,029-$799,219). Healthcare utilization was lower among recipients of matched sibling donor grafts and those with low severity disease compared to those with other types of donor and disease severity types (P<0.001 and P=0.022, respectively); no association was demonstrated with late transplantation (P=0.775). Among patients with 2-year pre- and post-transplant data (n=41), early transplantation was associated with significant reductions in admissions (P<0.001), length of stay (P<0.001), and cost (P=0.008). Early transplant outcomes need to be studied prospectively in young children without severe disease and an available matched sibling to provide conclusive evidence for the superiority of this approach. Reduced post-transplant healthcare utilization inpatient care indicates that transplantation may provide a sustained decrease in healthcare costs over time. Abstract source Full text

Hydroxyurea has proven clinical benefits and is recommended to be offered to all children with sickle cell anemia (SCA), but the optimal dosing regimen remains controversial. Induction of red blood cell fetal hemoglobin (HbF) by hydroxyurea appears to be dose-dependent. However, it is unknown whether maximizing HbF% improves clinical outcomes. HUSTLE (NCT00305175) is a prospective observational study with a primary goal of describing the long-term clinical effects of hydroxyurea escalated to maximal tolerated dose (MTD) in children with SCA. In 230 children, providing 610 patient-years of follow up, the mean attained HbF% at MTD was >20% for up to 4 years of follow-up. When HbF% values were <=20%, children had twice the odds of hospitalization for any reason (P < .0001), including vaso-occlusive pain (P < .01) and acute chest syndrome (ACS) (P < .01), and more than four times the odds of admission for fever (P < .001). Thirty day readmission rates were not affected by HbF%. Neutropenia (ANC <1000 × 106 /L) was rare (2.3% of all laboratory monitoring), transient, and benign. Therefore, attaining HbF >20% was associated with fewer hospitalizations without significant toxicity. These data support the use of hydroxyurea in children, and suggest that the preferred dosing strategy is one that targets a HbF endpoint >20%. Abstract source Full text

The prognosis of sickle cell anemia (SCA), initially disastrous in the severe forms of the disease, has greatly improved, leading to increased life expectancy. More than 95% to 99% of the children diagnosed with SCA in developed countries will become young adults, reaching reproductive age and able to consider having children of their own. Hydroxyurea (HU) is the main therapy that has considerably modified the prognosis of SCA, allowing, with good compliance, a substantial decrease in morbidity and mortality and significant improvement in quality of life. Only 3 groups, including our own, have reported the potentially detrimental effect of HU on sperm parameters, when initiated in adult patients. These retrospective studies were performed among as few as 8 participants, without any comparative semen assessment before initiation of HU in 7 participants. On the basis of this observation, a prospective multicenter study was designed to assess the effect of 6 months of HU treatment (representing 2 complete cycles of spermatogenesis) on total sperm count (TSC; millions per ejaculate) in 35 men with severe forms of SCA. Abstract source Full text

Limited evidence guides opioid dosing strategies for acute Sickle Cell (SCD) pain. We compared two National Heart, Lung and Blood (NHBLI) recommended opioid dosing strategies (weight-based vs. patient-specific) for ED treatment of acute vaso-occlusive episodes (VOE). A prospective randomized controlled trial (RCT) was conducted in two ED's. Adults >= 21 years of age with SCD disease were eligible. Among the 155 eligible patients, 106 consented and 52 had eligible visits. Patients were pre-enrolled in the outpatient setting and randomized to one of two opioid dosing strategies for a future ED visit. ED providers accessed protocols through the electronic medical record. Change in pain score (0-100 mm VAS) from arrival to ED disposition, as well as side effects were assessed. 52 patients (median age was 27 years, 42% were female, and 89% black) had one or more ED visits for a VOE (total of 126 ED study visits, up to 5 visits/patient were included). Participants randomized to the patient-specific protocol experienced a mean reduction in pain score that was 16.6 points greater than patients randomized to the weight-based group (mean difference 95% CI = 11.3 to 21.9, P = 0.03). Naloxone was not required for either protocol and nausea and/or vomiting was observed less often in the patient-specific protocol (25.8% vs 59.4%, P = 0.0001). The hospital admission rate for VOE was lower for patients in the patient-specific protocol (40.3% vs 57.8% P = 0.05). NHLBI guideline-based analgesia with patient-specific opioid dosing resulted in greater improvements in the pain experience compared to a weight-based strategy, without increased side effects. Abstract source Full text

Background and Objectives: Hydroxyurea (HU) was recently described as a substitute for chronic transfusion for children with sickle cell disease (SCD) and abnormal transcranial Doppler (TCD) velocities who have received at least 1 year of transfusions. However, the role of HU in reverting elevated TCD velocities in patients not treated with transfusion is still debatable. The objective of the study was to examine whether HU influences the progression of TCD velocities in children with SCD. Patients and Methods: Children with SCD with at least 2 TCDs not less than 6 months apart were evaluated over 51 months. Time-averaged maximum mean (TAMM) velocities for the initial and the last transcranial Doppler examinations were noted and differences compared between HU and HU-naive groups. Results: Overall, 68.8% of the HU-group with elevated TCD velocities compared with 40.0% of the HU-naive experienced TCD reversal (P = .047). A higher proportion of the HU-naive group, 7 (14.3%) versus 9.8% of the HU group experienced TCD conversion. Those with initial conditional velocities in the HU-group experienced a significant reduction in TAMM velocities (from 176.8 ± 5.3 to 162.7 ± 13.9 cm/s, difference of 14.1 cm/s; P = .001) unlike those in the HU-naive group (176.3 ± 5.3 to 170.0 ± 18.6 cm/s, difference of 6.3 cm/s; P = .148). The change in the TAMM velocities was also significantly higher among the HU-group (14.1 ± 12.4 cm/s versus 6.3 ± 18.5 cm/s, P = .015). Conclusion: Our data suggest a beneficial role of HU in TCD velocity reduction in patients not treated with chronic transfusions, particularly among those with initial conditional TCD velocities. Abstract source Full text

Pain episodes occur for many preschoolers with sickle cell disease (SCD), but little is known about parent perceptions of managing pain episodes in young children. We surveyed parents of young children with SCD who had managed pain episodes in the past year to assess their management and satisfaction with their strategies, challenges of pain management, and interest in additional education. Parents were recruited from health maintenance visits at a SCD specialty clinic. Forty-two of 51 parents (82%) of 2- to-6-year-olds reported managing pain over the past year. Parents who had managed pain primarily reported using medications. These parents reported at least moderate satisfaction with current management strategies and resources. At least one-third of parents found each facet of pain management queried as at least somewhat challenging. Identifying when their child was in pain, encouraging functional activities, and managing irritable behavior were reported as most challenging. Parents of young children with SCD reported interest in additional pain management education, which could promote better parent and child coping skills. Abstract source Full text

Among children with sickle cell disease (SCD), 40% of untreated children with elevated transcranial Doppler (TCD) velocities will develop stroke within 3 years. In 1998, the Stroke Prevention Trial in Sickle Cell Anemia (STOP) demonstrated that the use of chronic red blood cell transfusions in children with SCD with elevated TCD velocities in the middle cerebral artery decreased the risk of stroke by 92%. STOP, which revolutionized the outlook of children with SCD, relied on the assumption that TCD velocity predicts the risk for developing stenosing arteriopathy prior to the development of irreversible arteriopathy. Cerebral arteriopathy is a potent risk factor for primary and recurrent stroke in childhood, including among children with SCD. Abstract source Full text

Children with sickle cell anemia (SCA) suffer from a chronic state of inflammation due to repeated tissue insult from sickling red blood cells. The clinical consequences are severe and involve aberration of inflammatory systems, with associated increased activation of multiple cell types, including platelets, neutrophils, and eosinophils.1,2 The literature has described a reduction of inflammatory molecules by hydroxyurea, but results have been limited, and at times contradictory.3–8 In fact, some researchers reported that patients receiving hydroxyurea exhibited increased levels of interleukin (IL)-6 compared to untreated patients,9 while others reported a decrease in IL-6 levels in patients after initiating hydroxyurea therapy,10 albeit neither finding reached statistical significance (perhaps due to small study numbers). Herein, we address discrepancies by reporting a comprehensive study in which 214 patients with SCA were assessed, 122 of whom were sampled longitudinally. We compared patients on hydroxyurea (both initial and sustained therapy) with patients on chronic blood transfusions or no treatment. In grouped analyses, hydroxyurea proved to be the better treatment for reduction of inflammatory molecules. During the 2-year observation period, children continued to benefit from hydroxyurea treatment, although they did not achieve profiles similar to those of healthy controls. Patients receiving continuous chronic blood transfusion therapy or no treatment showed fewer reductions in factor levels compared to hydroxyurea. In total, our data illustrated the long-term, but incomplete benefit of hydroxyurea for reduction of inflammatory molecules in patients with SCA. Abstract source Full text