Abstract
BACKGROUND: Pediatric patients with sickle cell disease (SCD) experience a high level of pain, which is often chronic and recurrent and results in impaired health-related quality of life (HRQOL). Patients with SCD also report a significant degree of sleep disturbance and fatigue associated with their chronic disease. The objective of the present study is to investigate the effects of pain, sleep disturbance, and general fatigue in a serial (sequential) multiple mediator model analysis predicting overall generic HRQOL in pediatric patients with SCD from their perspective. METHODS: The Pain Scale from the PedsQL Sickle Cell Disease Module, General Fatigue Scale and Sleep Disturbance Item from the PedsQL Multidimensional Fatigue Scale, and the PedsQL 4.0 Generic Core Scales were completed in a multisite national study by 227 pediatric patients with SCD aged 5-18 years. Hierarchical multiple regression and serial multiple mediator model analyses were conducted to test the percent variability accounted for and the mediating effects of sleep disturbance and general fatigue in the association between SCD pain and generic HRQOL. RESULTS: Pain predictive effects on generic HRQOL were serially mediated by sleep disturbance and general fatigue. In a hierarchical multiple regression analysis controlling for age and sex, pain, sleep disturbance, and general fatigue accounted for 63% of the variance in pediatric patient-reported generic HRQOL (P < 0.001), demonstrating a large effect size. CONCLUSION: The mechanisms of the predictive effects of SCD-specific pain on generic HRQOL in pediatric patients with SCD are explained in part by the serial multiple mediator effects of sleep disturbance and general fatigue. Recognizing the multiple mediators of SCD-specific pain on generic HRQOL from the perspective of pediatric patients with SCD may aid future clinical research and practice to address impaired daily functioning through more comprehensive treatment approaches that include targeted symptom-specific interventions for pain, sleep disturbance, and fatigue.