Prevalence of raised body mass index in paediatric sickle cell disease.

AIM: Children with sickle cell disease (SCD) have historically weighed less than their healthy peers. More recently, a retrospective chart review from six institutions in New England reported nearly one-quarter of children and adolescents with SCD had raised body mass index (BMI). This study aimed to examine rates of children with SCD with raised BMI in Mississippi compared to state and national norms and assess the correlation between haemoglobin and BMI. METHODS: A retrospective chart review of paediatric patients with SCD at the University of Mississippi Medical Center (UMMC) was conducted using data from the most recent clinic visit. Mississippi and national weight status estimates for youth 10-17 years were obtained from the 2016-2017 National Survey of Children's Health. RESULTS: For youth 10-17 years with SCD (n = 345), 21.4.% of children with SS/Sß° and 36.1% with SC/Sß+ had raised BMI compared to Mississippi and national rates, 39.2 and 31%, respectively. The prevalence of children with raised BMI with SC/Sß+ did not differ from state and national rates, while children with SS/Sß° were half as likely as their Mississippi peers to have raised BMI. Haemoglobin levels were different among children with SCD who had low BMI (8.80 g/dL), average BMI (9.2 g/dL) and raised BMI (10.5 g/dL) (P < 0.001). CONCLUSIONS: Children with SCD evaluated at UMMC have similar rates of raised BMI compared to state and national norms. Children with raised BMI have higher mean haemoglobin levels compared to children with SCD with low or average BMI. IMPLICATIONS AND CONTRIBUTION: Historically, patients with SCD have been underweight and normal weight. Our paediatric and adolescent patients with SCD now have prevalence rates of raised BMI that approach state and national rates. Further work must be done to determine whether this reflects healthier children with SCD or raises concerns about life-style-related comorbidities.

Daily Associations between Child and Parent Psychological Factors and Home Opioid Use in Youth with Sickle Cell Disease.

BACKGROUND: Opioid analgesics are frequently used in the home setting to manage episodic pain in youth with sickle cell disease (SCD). Given the risk of adverse side effects, including constipation and sedation, understanding factors associated with at-home opioid use is important for maximizing pain relief while minimizing negative side effects. PURPOSE: The present study aimed to evaluate the relationship between individual psychological factors (pain catastrophizing and negative affect), caregiver psychological factors (catastrophizing about child's pain and caregiver negative affect), and home opioid use in youth with SCD. METHODS: Youth with SCD (n = 32) and a caregiver (n = 28) recruited during a routine outpatient hematology visit completed electronic 14 day diaries assessing pain, opioid use, and psychological factors. RESULTS: Approximately 28% of youth (n = 9) reported pain ≥50% of diary days and a third of youth (n = 11, 34%) used opioid analgesics at least one of the diary days. The number of days opioid analgesics were used ranged from 0 to 7 (50% of diary days). Results from generalized linear mixed models indicated greater child negative affect accounted for increased odds of opioid use on a given day when accounting for pain intensity. Greater caregiver catastrophizing about children's pain was also associated with increased odds of children's opioid use. CONCLUSIONS: Child and parent psychological factors relate to child opioid use at home for SCD-related pain. Future research is warranted in larger samples to identify targets for interventions to enhance pain management while reducing opioid-related risk and side effects.

Physical Activity and Pain in Youth With Sickle Cell Disease.

Study objectives were to examine the relationships between physical activity, pain, and psychological distress in youth 8 to 17 years of age with sickle cell disease. Participants were 206 youth with sickle cell disease (M = 11.73 years, 54.9% female, 99.5% African American). Caregivers and youth completed a clinical psychosocial screening battery. Results revealed frequent pain (37.6%), moderate median pain intensity, and elevated median pain interference in youth. Lower caregiver-reported physical activity was associated with worse pain outcomes. Increased anxiety was also associated with worse pain outcomes. A better understanding of the relationship between physical activity/inactivity and pain will guide multifactorial treatment interventions.

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial).

Blood cell membranes in sickle cell disease (SCD) have low docosahexaenoic acid (DHA). DHA treatment reduces sickle cell crisis (SCC) rate and ameliorates the inflammation, oxidative stress, and hypercoagulable state of SCD. SC411 is a novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced Lipid Technology) that enhances DHA bioavailability. The SCOT trial investigated the effect of 3 different doses of SC411 on clinical and biochemical endpoints in 67 children with SCD (5-17 years old). Seventy-six percent of subjects were also receiving hydroxyurea. After 4 weeks of treatment with SC411 at 20, 36, and 60 mg DHA/kg per day or placebo a statistically significant (P < .001) mean percentage increase of blood cell membrane DHA and eicosapentaenoic acid was seen vs baseline: 109.0% (confidence interval [CI], 46.7-171.3), 163.8% (CI, 108.3-219.2), 170.8% (CI, 90.2-251.4), and 28.6% (CI, 250.1 to 107.3), respectively. After 8 weeks of treatment, statistically significant changes vs placebo were also observed in D-dimer (P = .025) and soluble E-selectin (P = .0219) in subjects exposed to 36 mg/kg. A significant increase in hemoglobin was observed against placebo in subjects receiving 20 mg DHA/kg per day (P = .039). SC411 significantly reduced electronic diary recorded SCC, analgesic use at home, and days absent from school because of sickle cell pain. The lower rate of clinical SCC observed in the pooled active groups vs placebo did not reach statistical significance (rate ratio, 0.47; 95% CI, 0.20-1.11; P = .07). All tested doses were safe and well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT02973360.

Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study.

An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity. Nearly all newborns were treated with phototherapy (93%), and many were treated with exchange transfusions (46%). Children age 5 years and younger were often transfused until splenectomy. Splenectomy (150 [59%] of 254 patients) was associated with a median increase in hemoglobin of 1.6 g/dL and a decreased transfusion burden in 90% of patients. Predictors of a response to splenectomy included higher presplenectomy hemoglobin (P = .007), lower indirect bilirubin (P = .005), and missense PKLR mutations (P = .0017). Postsplenectomy thrombosis was reported in 11% of patients. The most frequent complications included iron overload (48%) and gallstones (45%), but other complications such as aplastic crises, osteopenia/bone fragility, extramedullary hematopoiesis, postsplenectomy sepsis, pulmonary hypertension, and leg ulcers were not uncommon. Overall, 87 (34%) of 254 patients had both a splenectomy and cholecystectomy. In those who had a splenectomy without simultaneous cholecystectomy, 48% later required a cholecystectomy. Although the risk of complications increases with severity of anemia and a genotype-phenotype relationship was observed, complications were common in all patients with PK deficiency. Diagnostic testing for PK deficiency should be considered in patients with apparent congenital hemolytic anemia and close monitoring for iron overload, gallstones, and other complications is needed regardless of baseline hemoglobin. This trial was registered at www.clinicaltrials.gov as #NCT02053480.

Children with sickle cell anemia with normal transcranial Doppler ultrasounds and without silent infarcts have a low incidence of new strokes.

In a prospective cohort study, we tested the hypothesis that children with sickle cell anemia (SCA) with normal transcranial Doppler ultrasound (TCD) velocities and without silent cerebral infarcts (SCIs) would have a lower incidence rate of new neurological events (strokes, seizures or transient ischemic attacks) compared to children with normal TCD measurements and SCIs, not receiving regular blood transfusions. Nonrandomized participants from the silent cerebral infarct transfusion (SIT) Trial who had screening magnetic resonance imaging (MRI) of the brain and normal TCD measurements were included. Follow-up ended at the time of first neurological event (stroke, seizure or transient ischemic attack), start of regular blood transfusion, or loss to follow-up, whichever came first. The primary endpoint was a new neurological event. Of 421 participants included, 68 had suspected SCIs. Mean follow-up was 3.6 years. Incidence rates of new neurological events in nontransfused participants with normal TCD values with SCIs and without SCIs were 1.71 and 0.47 neurological events per 100 patient-years, respectively, P = .065. The absence of SCI(s) at baseline was associated with a decreased risk of a new neurological event (hazard ratio 0.231, 95% CI 0.062-0.858; P = .029). Local pediatric neurologists examined 67 of 68 participants with suspected SCIs and identified 2 with overt strokes classified as SCIs by local hematologists; subsequently one had a seizure and the other an ischemic stroke. Children with SCA, without SCIs, and normal TCD measurements have a significantly lower rate of new neurological events when compared to those with SCIs and normal TCD measurements. Pediatric neurology assessment may assist risk stratification.

Recurrent Acute Chest Syndrome in Pediatric Sickle Cell Disease: Clinical Features and Risk Factors.

Acute chest syndrome (ACS) is a common and serious lung complication in sickle cell disease. A retrospective medical chart review was performed over a 6-year period in all pediatric ACS patients to investigate whether factors during the initial hospitalization were associated with recurrent ACS episodes. There were 386 episodes of ACS: 149 had only 1 episode of ACS, and 76 had >1 episode of ACS; 172 (76.4%) had hemoglobin SS, and 39 (17.3%) had hemoglobin SC. The most common presenting features were fever (83%), pain (70%), and cough (61%), which changed with the number of ACS episodes. Children <4 years old were at greatest risk of recurrent ACS (P=0.018). In addition, history of asthma (adjusted incident rate ratio [IRR]=1.52; 95% confidence interval [CI], 1.22-1.98; P<0.0001), shortness of breath (IRR, 1.29; 95% CI, 1.02-1.62; P=0.033), and length of hospital stay (IRR, 1.04; 95% CI, 1.01-1.08; P=0.017) were significantly associated with prospective ACS events. Multiple episodes of ACS are common in sickle cell disease, and certain risk factors during the initial hospitalization are associated with recurrent ACS.