Gaps during Pediatric to Adult Care Transfer Escalate Acute Resource Utilization in Sickle Cell Disease.

Guidelines recommend transfer to adult healthcare within six months of completing pediatric care, however this has not been studied in sickle cell (SCD). We hypothesized that longer transfer gaps are associated with increased resource utilization. Transfer gaps were defined as the time between the last pediatric and first adult visits. We estimated the association between varying transfer gaps and the rate of inpatient, emergency department (ED), and outpatient visits using negative binomial regression. Healthcare utilization was evaluated in a mid-south comprehensive program for a follow-up period of up to eight years (2012-2020) and also restricted to the first two years of adult healthcare. In total, 183 young adults (YAs) with SCD (51% male, 67% HbSS/HbSß0-thalassemia) transferred to adult healthcare between 2012-2018. YAs with transfer gaps ≥6 months compared to <2 months had 2.01 (95%CI: 1.31, 3.11) times the rate of hospitalizations in the 8-year follow-up and 1.89 (95%CI: 1.17, 3.04) when restricted to the first two years of adult healthcare. In the first two years of adult care, those with transfer gaps ≥6 months compared to <2 months, had 1.75 (95%CI: 1.10, 2.80) times the rate of ED encounters. Those with gaps ≥2 to <6 months compared to <2 months had 0.71 (95%CI: 0.53, 0.95) times the rate of outpatient visits. Among YAs with SCD, a longer transfer gap was associated with increased inpatient and decreased outpatient encounters in adult healthcare and more ED encounters in the first two years of adult healthcare. Strategies to reduce transfer gaps are needed.

Hydroxyurea at escalated dose versus fixed low-dose hydroxyurea in adults with sickle cell disease.

Hydroxyurea reduces the frequency of vaso-occlusive complications, increases hemoglobin, and decreases mortality in sickle cell disease (SCD). Although current guidelines recommend escalation to maximum tolerated dose (MTD), the use of fixed low-dose hydroxyurea is common in low-resource countries. We conducted a systematic review and meta-analysis to evaluate the efficacy of escalated doses versus fixed low-dose of hydroxyurea in adults with SCD. Nine studies were included in the quantitative synthesis, four evaluating fixed low-dose and five evaluating escalated doses of hydroxyurea. Average daily doses of hydroxyurea in the fixed low-dose and escalated dose studies were ~10 and 22 mg/kg, respectively. There was no difference in the estimate of vaso-occlusive crisis rate between escalated and fixed low-dose studies (p = .73). The mean difference in hemoglobin from baseline to follow-up was greater for fixed low-dose than escalated dose studies (1.07 g/dL vs. 0.54 g/dL, p = .01). No difference was seen in the mean estimate of fetal hemoglobin. Despite limited eligible studies and substantial heterogeneity of effect between the studies for several outcomes, there appears to be clinical equipoise regarding the most appropriate hydroxyurea dosing regimen in adults with SCD. Controlled studies of hydroxyurea at MTD versus fixed low-dose in adults with SCD are required.

Gene therapy in sickle cell disease: Attitudes and informational needs of patients and caregivers.

BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder that results in serious morbidity and early mortality. Novel therapies for SCD, most notably genetic therapies (GTs) and HLA-mismatched donor hematopoietic cell transplantation, are in clinical trials. While potentially curative, these interventions are some of the most intensive treatments for SCD and are associated with serious and life-altering side effects, which may manifest several years after treatment. Little is known about knowledge, beliefs, and attitudes of individuals with SCD, or their caregivers, toward existing and these emerging therapies. METHODS: Patients with SCD at least 13 years of age (n = 66) and caregivers (n = 38) were surveyed about knowledge, attitudes, and beliefs surrounding treatments for SCD. RESULTS: Only 4.8% felt "extremely knowledgeable" about GT for SCD while the majority (63.4%) reported little knowledge. Overall, health literacy was low among respondents. Most respondents had a neutral attitude regarding the safety of GT for SCD, and whether it was a good treatment for the disorder (56.7% and 58.6%, respectively). Only a few respondents endorsed the idea that GT was "unsafe" or "not a good treatment" (5.8% and 4.8%, respectively). There was an association between increasing knowledge about GT and agreement that it is safe (p = .012) and a good treatment for SCD (p = .031). CONCLUSIONS: Given that very few patients with SCD feel knowledgeable about GT and a majority have neutral feelings about the safety and utility of this new approach, culturally appropriate patient-centered education is urgently needed as these treatments get regulatory approval and proceed to the clinic.