New FRS studies were carried out using the complementary grating model. Data obtained at higher sensitivity confirm the non-Arrhenius behavior reported previously for MR in nematic 5CB. The results highlight the importance of accounting for complementary gratings effects for accurate FRS measurements in liquid-crystal systems.

Objective: To test the hypothesis that caregivers' or adult participants' low ratings of provider communication are associated with more hospital admissions among adults and children with sickle cell disease (SCD), respectively. Secondarily, we determined whether there was an association between the caregivers' or participants' health literacy and rating of providers' communication. Methods: Primary data were collected from participants through surveys between 2014 and 2016, across six sickle cell centers throughout the U.S. In this cross-sectional cohort study, 211 adults with SCD and 331 caregivers of children with SCD completed surveys evaluating provider communication using the Consumer Assessment of Healthcare Providers and Systems (CAHPS), healthcare utilization, health literacy, and other sociodemographic and behavioral variables. Analyses included descriptive statistics, bivariate analyses, and logistic regression. Results: Participants with better ratings of provider communication were less likely to be hospitalized (odds ratio (OR) = 0.54, 95% confidence interval (CI) = [0.35, 0.83]). Positive ratings of provider communication were associated with fewer readmissions for children (OR = 0.23, 95% CI = [0.09, 0.57]). Participants with better ratings of provider communication were less likely to rate their health literacy as lower (regression coefficient (B) = -0.28, 95% CI = [-0.46, -0.10]). Conclusions: Low ratings of provider communication were associated with more hospitalizations and readmissions in SCD, suggesting the need for interventions targeted at improving patient-provider communication which could decrease hospitalizations for this population.

Abstract

Sickle cell disease (SCD) is a genetic disorder affecting 100 000 people with an estimated annual medical cost of $3 billion in the United States; however, the economic impact on patients is not well described. We aimed to examine the indirect economic burden and test the hypothesis that socioeconomic status and greater social vulnerability risks are associated with increased absenteeism and employment loss. We surveyed adults and caregivers of children with SCD at 5 US centers from 2014 to 2021. Logistic regression models were used to examine the associations of employment loss and missed days of work with demographics and social determinants. Indirect costs were estimated by multiplying the self-reported missed days of work and job loss by 2022 average wages by the state of the participating institution. Of the 244 participants, 10.3% reported employment loss in the last 5 years, and 17.5% reported missing 10 or more days of work. Adults had 3 times more employment loss compared with caregivers of children with SCD (OR, 3.18; 95% CI, 1.12-9.01) but fewer missed days of work (OR, 0.24; 95% CI, 0.11-0.0.51). Participants who did not live with a partner reported increased employment loss (OR, 4.70; 95% CI, 1.04-21.17) and more missed days of work (OR, 4.58; 95% CI, 1.04-20.15). The estimated annual indirect economic burden was $2 266 873 ($9290 per participant). Adults with SCD and caregivers of children with SCD commonly report employment loss and missed days of work as important risk factors. The high indirect economic burden suggests that future economic evaluations of SCD should include SCD-related indirect economic burden.

Ability to accurately attribute adverse events post–gene therapy is required to describe the benefit-risk of these novel treatments. A SCD patient developed myelodysplastic syndrome post-LentiGlobin treatment; we show how insertional oncogenesis was excluded as the cause.

Objective

Hospital admissions are significant events in the care of individuals with sickle cell disease (SCD) due to associated costs and potential for quality of life compromise.

Methods

This cross-sectional cohort study evaluated risk factors for admissions and readmissions between October 2014 and March 2016 in adults with SCD (n = 201) and caregivers of children with SCD (n = 330) at six centres across the U.S. Survey items assessed social determinants of health (e.g. educational attainment, difficulty paying bills), depressive symptoms, social support, health literacy, spirituality, missed clinic appointments, and outcomes hospital admissions and 30-day readmissions in the previous year.

Results

A majority of adults (64%) and almost half of children (reported by caregivers: 43%) were admitted, and fewer readmitted (adults: 28%; children: 9%). The most common reason for hospitalization was uncontrolled pain (admission: adults: 84%, children: 69%; readmissions: adults: 83%, children: 69%). Children were less likely to have admissions/readmissions than adults (Admissions: OR: 0.35, 95% CI: [0.23,0.52]); Readmissions: 0.23 [0.13,0.41]). For all participants, missing appointments were associated with admissions (1.66 [1.07, 2.58]) and readmissions (2.68 [1.28, 6.29]), as were depressive symptoms (admissions: 1.36 [1.16,1.59]; readmissions: 1.24 [1.04, 1.49]). In adults, difficulty paying bills was associated with more admissions, (3.11 [1.47,6.62]) readmissions (3.7 [1.76,7.79]), and higher spirituality was associated with fewer readmissions (0.39 [0.18,0.81]).

Discussion

Missing appointments was significantly associated with admissions and readmissions. Findings confirm that age, mental health, financial insecurity, spirituality, and clinic attendance are all modifiable factors that are associated with admissions and readmissions; addressing them could reduce hospitalizations.

lovo-cel (bb1111; LentiGlobin for sickle cell disease [SCD]) gene therapy (GT) comprises autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified β-globin gene (β^A-T87Q ) to produce anti-sickling hemoglobin (HbA^T87Q ). The efficacy and safety of lovo-cel for SCD are being evaluated in the ongoing phase 1/2 HGB-206 study (ClinicalTrials.gov: NCT02140554). The treatment process evolved over time, using learnings from outcomes in the initial patients to optimize lovo-cel's benefit-risk profile. Following modest expression of HbA^T87Q in the initial patients (Group A, n = 7), alterations were made to the treatment process for patients subsequently enrolled in Group B (n = 2, patients B1 and B2), including improvements to cell collection and lovo-cel manufacturing. After 6 months, median Group A peripheral blood vector copy number (≥0.08 c/dg) and HbA^T87Q levels (≥0.46 g/dL) were inadequate for substantial clinical effect but stable and sustained over 5.5 years; both markedly improved in Group B (patient B1: ≥0.53 c/dg and ≥2.69 g/dL; patient B2: ≥2.14 c/dg and ≥6.40 g/dL, respectively) and generated improved biologic and clinical efficacy in Group B, including higher total hemoglobin and decreased hemolysis. The safety of the lovo-cel for SCD treatment regimen largely reflected the known side effects of HSPC collection, busulfan conditioning regimen, and underlying SCD; acute myeloid leukemia was observed in two patients in Group A and deemed unlikely related to insertional oncogenesis. Changes made during development of the lovo-cel treatment process were associated with improved outcomes and provide lessons for future SCD GT studies.

Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion-dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in children with TDT. Thirty-three children, ages 1 to 17 years, received bone marrow (BM) or umbilical cord blood (UCB) allografts. Median time to neutrophil engraftment was 13 days (range, 10 to 25) and 24 days (range, 18 to 49) and platelet engraftment 23 days (range, 12 to 46) and 50 days (range, 31 to 234) after BM and UCB allografts, respectively. With a median follow-up of 58 months (range, 7 to 79), overall and thalassemia-free survival was 82% (95% CI, .64% to .92%) and 79% (95% CI, .6% to .9%), respectively. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) after BM and UCB allografts was 24% and 44%; the 2-year cumulative incidence of chronic extensive GVHD was 29% and 21%, respectively; 71% of BM and 91% of UCB recipients discontinued systemic immunosuppression by 2 years. Six patients who had Pesaro risk class 2 (n = 5) and class 3 (n = 1) died of GVHD (n = 3), viral pneumonitis (n = 2) and pulmonary hemorrhage (n = 1). Outcomes after this RIC compared favorably with URD HSCT outcomes for TDT and supported engraftment in 32 of 33 patients. Efforts to reduce GVHD and infectious complications are being pursued further.