Journal Article Annotations
2022, 1st Quarter
Annotations by Liz Prince, DO and C. Patrick Carroll, MD
Systematic review of 32 studies (published January 2000 to 2020) of patients with sickle cell disease (SCD) with overt stroke, silent cerebral infarct (SCI), and those with no known CNS complications. The review looks at outcomes for cognitive deficits as well as healthcare utilization and costs. Metanalysis of 10 of the studies in pediatric populations demonstrated full scale IQ was significantly lower for those with overt stroke vs. controls (patients with SCD but no known CNS complications) (-12.6), SCI vs controls (-5.7), as well as overt stroke vs SCI (-9.4) and any event vs controls (-7.6). The authors found that if children received hydroxyurea after a stroke, they had significantly less physician rated moderate-severe motor disability. Nine studies reported economic outcomes suggesting a substantial hospital length of stay and hospital costs were associated with treatment for the CNS complications of SCD.
Strength and weaknesses:
This is the largest and latest systematic review/meta-analysis of the effects of CNS complications from SCD. Looking at both cognitive and economic effects allowed for inclusion of a variety of studies and populations, though mostly pediatric. The authors themselves point out the minimal use of patient reported outcomes (PRO), like quality of life or productivity, which limits the ability to understand the impact of these cognitive deficits and economic burdens on patients and their families.
CNS complications are common in patients with SCD. In the most severe genotypes (sickle cell anemia) 11% of children will experience overt stroke before age 19, and 37% will experience SCI by age 14. Not only do the findings emphasize the need for improved treatments for sickle cell disease to prevent CNS complications, they highlight the need for further research on the functional impacts of these complications on patients and their families.
Soumitri Sil and colleagues present prospective data examining the impact of pain catastrophizing (self-reported rumination, magnification, and helplessness) on pain interference (self-reported functional impairment secondary to pain) in 63 youth with SCD and chronic pain. The hierarchical statistical model included baseline pain intensity, pain interference, pain-related catastrophizing, markers of SCD severity, and anxiety/depressive symptoms. In the full model, baseline pain catastrophizing was the only significant predictor of pain interference at 4 months. But when entered into the model as a block, anxiety/depressive symptoms did improve prediction of pain interference. Combined, depressive and anxiety symptoms and pain catastrophizing contributed almost as much predictive power to the model as baseline SCD and pain severity. In their discussion, the authors cite papers that suggest CBT to be effective for pain catastrophizing.
Strength and weaknesses:
Strengths include a rigorous longitudinal prospective study design controlling for baseline pain intensity and interference. Depressive symptom measures’ prediction of pain interference may be confounded by construct overlap with PROMIS Pediatric Pain Interference (which includes elements referencing sleep, energy, hedonic capacity, concentration, and irritability).
Depressive and anxiety symptoms, and particularly pain catastrophizing, are compelling targets for therapeutic interventions to treat chronic pain in SCD.