Biopsychosocial Predictors of Quality of Life in Paediatric Patients With Sickle Cell Disease

Sickle cell disease (SCD) refers to a group of inherited blood disorders with considerable morbidity that causes severe pain, reduces life expectancy, and requires significant self-management. Acute painful episodes are the hallmark of SCD, but persistent daily pain is also highly prevalent in this population. Characterising the impact and experience of SCD-related morbidity (i.e., sleep disruption, frequent emergency department visits, cognitive dysfunction) on health-related quality of life (HRQOL) requires multiple assessment methods to best capture the underlying mechanisms. To gain a greater understanding of the effect of common symptom categories on HRQOL and to determine potential pain coping targets, the present study investigated whether demographic, socioeconomic, sleepiness, pain burden, frequency of emergency department (ED) visits, and cognition predicted HRQOL in a paediatric sample of patients with SCD. Our study was a secondary analysis of baseline assessment data of children with SCD aged 8-15 years (n = 30) in the Prevention of Morbidity in Sickle Cell Anaemia Phase 2b (POMSb2) randomised controlled clinical trial of auto-adjusting continuous positive airways pressure. Patients completed cognitive testing (IQ, Processing Speed Index, Delis-Kaplan Executive Function Scale (DKEFS) Tower, Conner's Continuous Performance Test), sleepiness (Epworth Sleepiness Scale), and HRQOL (PedsQL Sickle Cell Module) at baseline. Patients reported pain burden (Sickle Cell Pain Burden Inventory-Youth) each month over 8 visits. Caregivers provided demographic information and reported their child's executive function (Behavioural Rating Inventory of Executive Function) at baseline. Data from our analysis demonstrated that demographic factors (i.e., age, gender, level of neighbourhood deprivation) and treatment variables (i.e., hydroxyurea use) did not independently predict HRQOL, and laboratory values (i.e., haemoglobin, haematocrit, mean oxygen saturation) were not significantly correlated with HRQOL (ps > 0.05). However, sleepiness, pain burden, ED visits, and executive dysfunction independently predicted HRQOL (R 2 = 0.66) with large effects (η2 = 0.16 to 0.32). These findings identify specific, measurable symptom categories that may serve as targets to improve HRQOL that are responsive to change. This knowledge will be useful for multimodal interventions for paediatric patients with SCD that include sleep management, pain coping strategies, and executive function training

Outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion

There are over 12,000 people with sickle cell disease (SCD) in the UK, and 4–12% of patients who develop Sickle Cell Nephropathy (SCN) progress to End Stage Renal Disease (ESRD). Renal transplantation offers the best outcomes for these patients with but their access to transplantation is often limited. Regular automated exchange blood transfusions (EBT) reduce the complications of SCD and may improve outcomes. However, concerns over alloimmunisation limit its widespread implementation. In this retrospective multicenter study, data were collected on 34 SCD patients who received a kidney transplant across 6 London Hospitals between 1997 and 2017. 20/34 patients were on an EBT program, pre or post renal transplantation. Overall patient and graft survival were inferior to contemporaneous UK data in the ESRD population as a whole, a finding which is well-recognised. However, patient survival (CI 95%, p = 0.0032), graft survival and graft function were superior at all time-points in those who received EBT versus those who did not. 4/20 patients (20%) on EBT developed de novo donor specific antibodies (DSAs). 3/14 patients (21%) not on EBT developed de novo DSAs. The incidence of rejection in those on EBT was 5/18 (28%), as compared with 7/13 (54%) not on EBT. In conclusion, our data, while limited by an inevitably small sample size and differences in the date of transplantation, do suggest that long-term automated EBT post renal transplant is effective and safe, with improvement in graft and patient outcomes and no increase in antibody formation or graft rejection

White Matter Integrity and Processing Speed in Sickle Cell Anemia

Objective The purpose of this retrospective cross-sectional study was to investigate whether changes in white matter integrity are related to slower processing speed in sickle cell anemia. Methods Thirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8–37 years) underwent cognitive assessment using the Wechsler scales and 3-tesla MRI. Tract-based spatial statistics analyses of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed. Results Processing speed index (PSI) was lower in patients than controls by 9.34 points (95% confi- dence interval: 4.635–14.855, p = 0.0003). Full Scale IQ was lower by 4.14 scaled points (95% confidence interval: −1.066 to 9.551, p = 0.1), but this difference was abolished when PSI was included as a covariate (p = 0.18). There were no differences in cognition between patients with and without silent cerebral infarction, and both groups had lower PSI than controls (both p < 0.001). In patients, arterial oxygen content, socioeconomic status, age, and male sex were identified as predictors of PSI, and correlations were found between PSI and DTI scalars (fractional anisotropy r = 0.614, p < 0.00001; r = −0.457, p < 0.00001; mean diffusivity r = −0.341, p = 0.0016; radial diffusivity r = −0.457, p < 0.00001) and NODDI parameters (intracellular volume fraction r = 0.364, p = 0.0007) in widespread regions. Conclusion Our results extend previous reports of impairment that is independent of presence of infarction and may worsen with age. We identify processing speed as a vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide evidence that reduced processing speed is related to the integrity of normal-appearing white matter using microstructure parameters from DTI and NODDI