Gaps during pediatric to adult care transfer escalate acute resource utilization in sickle cell disease.

ABSTRACT: Guidelines recommend transfer to adult health care within 6 months of completing pediatric care; however, this has not been studied in sickle cell disease (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 rates of inpatient, emergency department (ED), and outpatient visits, using negative binomial regression. Health care utilization was evaluated in a mid-south comprehensive program for a follow-up period of up to 8 years (2012-2020) and was restricted to the first 2 years of adult health care. In total, 183 young adults (YAs) with SCD (51% male, 67% HbSS/HbSß0-thalassemia) were transferred to adult health care between 2012 and 2018. YAs with transfer gaps ≥6 months compared with <2 months had 2.01 (95% confidence interval [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 2 years of adult health care. In the first 2 years of adult care, those with transfer gaps ≥6 months compared with <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 with <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 health care and more ED encounters in the first 2 years of adult health care. Strategies to reduce the transfer gaps are needed.

A multilevel mHealth intervention boosts adherence to hydroxyurea in individuals with sickle cell disease.

Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU Toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval. We enrolled 293 patients (51% male; median age 27.5 years, 86.8% HbSS/HbSß0-thalassemia). The mean change in PDC among 235 evaluable subjects increased (39.7% to 56.0%; P < 0.001) and sustained (39.7% to 51.4%, P < 0.001). Mean HbF increased (10.95% to 12.78%; P = 0.03). Self-reported pain frequency reduced (3.54 to 3.35 events/year; P = 0.041). InCharge Health was used ≥1 day by 199 of 235 participants (84.7% implementation; median usage: 17% study days; IQR: 4.8-45.8%). For individuals with ≥1 baseline admission for pain, admissions per 24 weeks declined from baseline through 24 weeks (1.97 to 1.48 events/patient, P = 0.0045) and weeks 25-36 (1.25 events/patient, P = 0.0015). PDC increased with app use (P < 0.001), with the greatest effect in those with private insurance (P = 0.0078), older subjects (P = 0.033), and those with lower pain interference (P = 0.0012). Of the 89 providers (49 hematologists, 36 advanced care providers, 4 unreported), only 11.2% used HU Toolbox ≥1/month on average. This use did not affect change in PDC. Tailoring mHealth solutions to address barriers to hydroxyurea adherence can potentially improve adherence and provide clinical benefits. A definitive randomized study is warranted. This trial was registered at www.clinicaltrials.gov as #NCT04080167.

Provider prescription of hydroxyurea in youth and adults with sickle cell disease: A review of prescription barriers and facilitators.

Sickle cell disease (SCD) is an inherited red blood cell disorder associated with frequent painful events and organ damage. Hydroxyurea (HU) is the recommended evidence-based treatment of SCD. However, among patients eligible for HU, prescription rates are low. Utilizing a scoping review approach, we summarized and synthesized relevant findings regarding provider barriers and facilitators to the prescription of HU in youth and adults with SCD and provided suggestions for future implementation strategies to improve prescription rates. Relevant databases were searched using specified search terms. Articles reporting provider barriers and/or facilitators to prescribing HU were included. A total of 10 studies met the inclusion criteria. Common barriers to the prescription of HU identified by providers included: doubts around patients' adherence to HU and their engaging in required testing, concerns about side effects, lack of knowledge, cost and patient concerns about side effects. Facilitators to the prescription of HU included beliefs in the effectiveness of HU, provider demographics and knowledge. Findings suggest significant provider biases exist, particularly in the form of negative perceptions towards patients' ability to adhere to taking HU and engaging in the required follow-up. Improving provider knowledge and attitudes towards HU and SCD may help improve low prescription rates.

Science Communication Training Imparts Confidence and Influences Public Engagement Activity.

The impacts of science are felt across all socio-ecological levels, ranging from the individual to societal. In order to adapt or respond to scientific discoveries, novel technologies, or biomedical or environmental challenges, a fundamental understanding of science is necessary. However, antiscientific rhetoric, mistrust in science, and the dissemination of misinformation hinder the promotion of science as a necessary and beneficial component of our world. Scientists can promote scientific literacy by establishing dialogues with nonexperts, but they may find a lack of formal training as a barrier to public engagement. To address this, the American Society for Biochemistry and Molecular Biology (ASBMB) launched the Art of Science Communication course in 2015 in order to provide scientists at all career stages with introductory science communication training. In 2020, we conducted a retrospective survey of former participants to evaluate how the course had impacted participants' science communication behaviors and their confidence engaging with nonexperts, as well as other benefits to their professional development. We found that scientists were significantly more likely to communicate with nonexpert audiences following the course compared to before (77% versus 51%; P < 0.0001). In addition, quantitative and qualitative data suggested that scientists were more confident in their ability to communicate science after completing the course (median of 8, standard deviation [SD] of 0.98 versus median of 5, SD of 1.57; P < 0.0001). Qualitative responses from participants supported quantitative findings. This suggested that the Art of Science Communication course is highly effective at improving the confidence of scientists to engage with the public and other nonexpert audiences regardless of career status. These data-driven perspectives provide a rationale for the implementation of broadly accessible science communication training programs that promote public engagement with science.

Pharmacist Effect on Discharge Follow-Up Education in Pediatric Oncology Outpatient Clinics: A Quality Improvement Study.

OBJECTIVE: We aimed to describe the effect of education provided by a clinical pharmacy specialist at a patient's follow-up appointment after discharge, and to assess caregiver satisfaction. METHODS: A single-center, quality improvement study was conducted. A standardized data collection tool was created to characterize interventions made by clinical pharmacy specialists during an outpatient clinic appointment scheduled shortly after discharge. Pediatric patients with cancer who met the following criteria were included: 1) initial diagnosis without receiving chemotherapy, 2) first course of chemotherapy after initial diagnosis or relapsed disease, and 3) post-hematopoietic stem cell transplantation or cellular therapy. A survey was provided to families after the follow-up discharge appointment to assess the caregiver's satisfaction of the new process. RESULTS: From January to May 2021, a total of 78 first-time discharge appointments were completed. The most common reason for follow-up was discharge after first course of chemotherapy (77%). The average duration of each appointment was 20 minutes (range, 5-65). The clinical pharmacy specialist made an intervention during 85% of appointments. The most common intervention made during the visit was reinforcement of medications (31%). Thirteen surveys were completed by caregivers; 100% of the caregivers reported the follow-up appointment was helpful. Additionally, they reported the most useful resource provided at discharge was the medication calendar (85%). CONCLUSIONS: Investing clinical pharmacy specialist time with patients and caregiver after discharge appears to have a meaningful effect on patient care. Caregivers report this process is helpful in better understanding their child's medications.

Social determinants of neurocognitive and academic performance in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is associated with poor neurocognitive outcomes due to biomedical and psychosocial factors. The aims of this study were to investigate associations between household and neighborhood socioeconomic status (SES) with cognitive and academic outcomes in SCD and to determine if these relationships were modified by sickle genotype, fetal hemoglobin, or age. PROCEDURE: We prospectively recruited patients to complete a battery of neurocognitive and academic measures. Household SES was measured using the Barratt Simplified Measure of Social Status, a composite index of parent education and occupation. The Social Vulnerability Index was used to classify individuals based on social vulnerabilities at the neighborhood level. RESULTS: Overall, 299 patients between the ages of 4 and 18 (mean = 11.4, standard deviation = 4.3) years diagnosed with SCD (57% SS/SB0 -thalassemia) completed testing. Stepwise multivariate models demonstrated that patients with low social vulnerability (i.e., high SES) at the neighborhood level displayed intelligence and math scores that were 4.70 and 7.64 points higher than those living in areas with moderate social vulnerability, respectively (p < .05). Reading performance did not differ based on neighborhood SES; however, the effect of neighborhood SES was dependent on age, such that older participants living in neighborhoods with moderate or high levels of social vulnerability displayed poorer reading scores than those with low social vulnerability (p < .05). CONCLUSIONS: This study identified patients with SCD at higher risk of poor academic performance based on SES. Interventions addressing academic difficulties should be offered to all children with SCD, but should be emergently offered to this subpopulation.

Sickle cell disease and social determinants of health: A scoping review.

Social determinants of health (SDoH) may impact outcomes in sickle cell disease (SCD). We conducted a comprehensive literature review of five electronic databases to elucidate the relationship between SDoH and SCD, and identify gaps in the literature. Our search yielded 59 articles, which we organized into five SDoH areas: Neighborhood and Built Environment, Health and Healthcare, Social and Community Context, Education, and Economic Stability. We found that social determinants, such as access to healthcare, were inconsistently evaluated. Improved recognition and understanding of SDoH should enhance the development of programs that directly address its detrimental effects on patients with SCD.

Working memory and school readiness in preschool children with sickle cell disease compared to demographically matched controls.

Children diagnosed with sickle cell disease (SCD) are at risk of the development of neurobehavioural problems early in life. Specific impairments in executive function skills, including working memory, have been documented in school-aged children with SCD. These executive skills are known to strongly contribute to early academic skills and preparedness for entering kindergarten. This study examined working memory and school readiness in preschool children with SCD compared to a healthy control group matched for race, sex and parent education. A total of 84 patients diagnosed with SCD (61.9% haemoglobin [Hb]SS/HbSß0 -thalassaemia) and 168 controls completed testing. The mean (SD) ages of patients and controls at testing were 4.53 (0.38) and 4.44 (0.65) years respectively. The SCD group performed worse than controls on measures of executive function, working memory and school readiness (p < 0.01; Cohen's D range: 0.32-0.39). Measures of working memory were associated with school readiness after accounting for early adaptive development. Multiple linear regression models among patients diagnosed with SCD revealed that college education of the primary caregiver was positively associated with school readiness (p < 0.001) after controlling for sex, genotype, age and early adaptive development. These results highlight the need to implement school readiness interventions in young children diagnosed with SCD emphasising executive function skills.

Internalizing Symptoms in Adolescents With Sickle Cell Disease.

OBJECTIVE: Sickle cell disease (SCD) is a genetic blood disorder that may affect patients' mood and behavior. However, measuring the prevalence of internalizing symptoms (anxiety and depression) in patients with SCD has been elusive. We assessed internalizing symptoms in adolescents with SCD to evaluate prevalence and to test whether neurocognitive performance and frequency of pain-related episodes were associated with internalizing concerns. METHODS: One hundred eighty-five patients (57% HbSS/HbSß0-thalassemia, 43% HbSC/HbSß+-thalassemia), ages 12-18 years, received a neuropsychological evaluation as a part of a larger cohort study. Internalizing symptoms were measured using the Behavior Assessment System for Children, Second or Third Edition. Scores on the depression and anxiety scales were compared to normative values using Wilcoxon signed rank test. Spearman correlations examined associations between neurocognitive performances and internalizing symptoms. Robust multivariable regression models measured associations between internalizing symptoms and age, sex, sickle genotype, total hemoglobin, fetal hemoglobin, socioeconomic status, and frequency of pain episodes. RESULTS: Parent- and self-reported ratings of internalizing symptoms were not elevated compared to normative expectations. Overall, 1.8% and 6.3% of the sample displayed clinically elevated symptoms of anxiety and depression based on self-report, respectively. There were no associations between internalizing symptoms and neurocognitive performance (all p > .05). In multivariable analyses, the frequency of pain episodes was positively associated with self-reported anxiety (p = .006) and parent-reported depressive symptoms (p = .017). CONCLUSIONS: Adolescents with SCD do not report elevated internalizing symptoms compared to normative expectations. Further research is needed to examine the trajectory of internalizing symptoms and the bidirectional relationship between pain and psychosocial functioning in SCD.

Assessment of transition readiness to predict health care utilization during transition to adult care in sickle cell disease.

BACKGROUND: Transition-age patients with sickle cell disease (SCD) are at risk for poor outcomes associated with incomplete transition readiness and neurocognitive deficits. Study objectives were to: 1) test if a SCD-specific measure of self-management skills was associated with transition outcomes and 2) evaluate if caregiver-reported executive functioning was associated with self-management skills and transition outcomes among youth with SCD. RESEARCH DESIGN AND METHODS: Youth/caregivers were selected from a longitudinal cohort study. Caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF); caregivers and youth completed the Self-Management Skills Checklist (SMSC) at a median age of 16.8 ± 0.6 years. Non-parametric tests compared SMSC and transition outcomes. Regression assessed the incremental validity of SMSC in predicting transition outcomes. RESULTS: In total, 95 participants (54% male, 55% severe genotype) completed the SMSC assessment. Most participants (87%) transferred to adult care within six months and 87% were retained for at least 12 months. BRIEF and caregiver-reported SMSC assessments were weakly, negatively correlated (ρ = -0.25, p = 0.0392) but were not significant in predicting transition outcomes (p > 0.05). CONCLUSIONS: The SMSC and executive function did not predict adult care engagement. Development of readiness assessments that predict care engagement and reflect self-efficacy is important for monitoring transition-aged patients with SCD.

Enuresis and Hyperfiltration in Children With Sickle Cell Disease.

Nocturnal enuresis is a common symptom in children with sickle cell disease (SCD). Risk factors for development of enuresis are currently unknown. An early manifestation of SCD-associated kidney damage is glomerular hyperfiltration. We test the hypothesis that in a pediatric SCD cohort, individuals with hyperfiltration are more likely to have nocturnal enuresis when compared to children without hyperfiltration. To assess the relationship between nocturnal enuresis and hyperfiltration, we retrospectively evaluated children with SCD enrolled in the Evaluation of Nocturnal Enuresis and Barriers to Treatment among Pediatric Patients with SCD study and prospectively identified children who reported nocturnal enuresis and were enrolled in the longitudinal cohort study Sickle Cell Clinical Research and Intervention Program. Nocturnal enuresis occurred in 46.5% of Pediatric Patients with Sickle Cell Disease participants and was more frequent in participants with HbSS/HbSß 0 thalassemia and in male participants. We did not identify an association between hyperfiltration from 3 to 5 years of age with the later development of enuresis. Severe SCD genotypes and male sex were associated with nocturnal enuresis after age 5 years. We could not identify additional renal or hematologic predictors associated with the diagnosis of nocturnal enuresis. Future studies should incorporate nonrenal risk factors into studies that predict development of enuresis.

Neurocognitive risk in sickle cell disease: Utilizing neuropsychology services to manage cognitive symptoms and functional limitations.

Sickle cell disease (SCD) is an inherited blood disorder that is associated with developmental delays and neurocognitive deficits. This review details key findings related to neurocognitive outcomes for children and adults with emphasis on the impact of neurological correlates and disease severity. Associations between neurocognition, demographic factors and social determinants of health are also reviewed. Emerging literature has reported on the neurocognitive impact of SCD in children and adolescents in Africa and Europe, including children from immigrant communities. Neurocognitive deficits are linked to poor functional outcomes, including transition from paediatric to adult care, medication adherence and unemployment. Integrating neuropsychology into multidisciplinary care for individuals with SCD can assist with identification and management of neurocognitive concerns, intervention development, individualized care plan development and continued multidisciplinary research.

Nocturnal Enuresis in Sickle Cell: Sociodemographic, Medical, and Quality of Life Factors.

OBJECTIVE: Nocturnal enuresis is more prevalent in youth with sickle cell disease (SCD) compared to the general population. The purpose of this study is to estimate prevalence of nocturnal enuresis using diagnostic criteria and identify associated sociodemographic, medical, and health-related quality of life (HRQOL) factors. METHODS: Youth with SCD (N = 248; ages 6.00-17.99 years) and their caregivers completed semi-structured interviews and questionnaires. HRQOL was measured using the Pediatric Quality of Life (PedsQL) Inventory. Medical information was abstracted from medical record. We generated multivariable logistic regression models to examine associations between factors and current nocturnal enuresis and nocturnal enuresis occurring any time in the past (lifetime). RESULTS: Among participants (mean age, 11.3 ± 3.6 years; 50.8% male), 21.4% reported current nocturnal enuresis and 46% reported lifetime nocturnal enuresis. Male sex [odds ratio (OR), 2.57; p = .001], difficulty arousing from sleep (OR, 3.57; p < .001), higher school functioning HRQOL (OR, 1.02; p = .014), and higher fetal hemoglobin levels (OR, 1.03; p = .048) were associated with lifetime nocturnal enuresis. Younger age (OR, 1.16; p = .005), higher youth-reported fatigue (OR, 1.01; p = .045), difficulty arousing from sleep (OR, 4.92; p < .001), and higher lactate dehydrogenase levels (OR, 1.00; p = .042) were associated with current nocturnal enuresis. CONCLUSIONS: Nocturnal enuresis is prevalent in youth with SCD and is associated with HRQOL, diminished sleep, greater fatigue, and disease severity markers. Routine assessment of sleep behaviors and fatigue are necessary when treating patients with SCD to understand the impact of nocturnal enuresis on HRQOL.

Neurocognitive functioning in preschool children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) experience neurodevelopmental delays; however, there is limited research with preschool-age children. This study examined neurocognitive risk and protective factors in preschoolers with SCD. PROCEDURE: Sixty-two patients with SCD (60% HbSS/HbSß0 -thalassemia; 40% HbSC/HbSß+ -thalassemia) between the ages of 3 and 6 years (mean = 4.77 years) received a neuropsychological evaluation as routine systematic surveillance. Patients were not selected for disease severity, prior central nervous system findings, or existing cognitive concerns. Thirty-four patients (82% HbSS/HbSß0 -thalassemia) were prescribed hydroxyurea (HU) at the time of their neuropsychological evaluation. On average, these patients had been prescribed HU at 2.15 (standard deviation = 1.45) years of age. The average dose was 28.8 mg/kg/day. Besides genotype, there were no group differences in medical or demographic factors based on HU treatment status. RESULTS: Patients with HbSS/HbSß0 -thalassemia scored below normative expectations on measures of intelligence, verbal comprehension, and school readiness (false discovery rate-adjusted p-value [pFDR ] < .05). Age, sickle genotype, and HU treatment exposure were not associated with measured neurocognitive outcomes (pFDR  > .05). Greater social vulnerability at the community level was associated with poorer performance on measures of intellectual functioning, verbal comprehension, visuomotor control, and school readiness, as well as parent report of executive dysfunction (pFDR  < .05). Greater household socioeconomic status was positively associated with academic readiness. CONCLUSIONS: Preschoolers with severe SCD (HbSS/HbSß0 -thalassemia) perform below age expectations on measures of intelligence and academic readiness. Sociodemographic factors were stronger drivers of neurocognitive performance than disease severity or disease-modifying treatment. Neurodevelopmental interventions targeting the home and broader community environment are needed.

Transition care continuity promotes long-term retention in adult care among young adults with sickle cell disease.

BACKGROUND/OBJECTIVES: Care continuity prevents increased health care utilization and mortality during transition from pediatric to adult care. Our program employs a co-located care delivery model, in which pediatric provider involvement continues during young adulthood. We tested the hypothesis that individuals who participated in the co-located model have greater retention in adult care compared to those who only received pediatric transition services. METHODS: This study consisted of 311 youth with SCD (51.4% male; 63.0% HbSS/HbSß0 -thalassemia) who transferred to adult care from 2007 to 2017. Retention was defined as continuation with an adult provider for ≥12 or ≥24 months post-pediatric care. Logistic regression estimated the association between co-location status and retention at 12 and 24 months. Logistic regression and t-tests were used to evaluate potential predictors of retention in adult care. RESULTS: Individuals who participated in the co-location model were 1.9 times more likely to remain in adult care 12 (95% CI: 1.01, 3.47) and 24 (95% CI: 1.01, 3.70) months post-pediatric care compared to those who did not participate. Individuals with HbSS/HbSß0 -thalassemia were 1.9 times more likely to be retained at 12 months compared to those with HbSC/HbSß+ -thalassemia/HbS/HPFH (95% CI: 1.12, 3.09). For every clinic encounter in the last 2 years of pediatric care, the odds of being retained at least 24 months after initiating adult care increased 1.1 times (95% CI: 1.02, 1.13). CONCLUSIONS: Continuity of providers from pediatric to adult care may increase long-term retention in adult care. Longitudinal monitoring of adult outcomes is critical to identifying the efficacy of transition services.

Genetic therapies for the first molecular disease.

Sickle cell disease (SCD) is a monogenic disorder characterized by recurrent episodes of severe bone pain, multi-organ failure, and early mortality. Although medical progress over the past several decades has improved clinical outcomes and offered cures for many affected individuals living in high-income countries, most SCD patients still experience substantial morbidity and premature death. Emerging technologies to manipulate somatic cell genomes and insights into the mechanisms of developmental globin gene regulation are generating potentially transformative approaches to cure SCD by autologous hematopoietic stem cell (HSC) transplantation. Key components of current approaches include ethical informed consent, isolation of patient HSCs, in vitro genetic modification of HSCs to correct the SCD mutation or circumvent its damaging effects, and reinfusion of the modified HSCs following myelotoxic bone marrow conditioning. Successful integration of these components into effective therapies requires interdisciplinary collaborations between laboratory researchers, clinical caregivers, and patients. Here we summarize current knowledge and research challenges for each key component, emphasizing that the best approaches have yet to be developed.

Feasibility of Medical Student Mentors to Improve Transition in Sickle Cell Disease.

OBJECTIVE: Advances in medical care have resulted in nearly 95% of all children with sickle cell disease (SCD) living to adulthood. There is a lack of effective transition programming, contributing to high rates of mortality and morbidity among adolescents and young adults (AYAs) during the transition from pediatric to adult healthcare. This nonrandomized study evaluated the feasibility, acceptability, and preliminary outcomes of a novel medical student mentor intervention to improve transition outcomes for AYA with SCD. METHODS: Eligible participants were ages 18-25 years, either preparing for transition or had transferred to adult care within the past year. Twenty-four AYA with SCD (Mage = 20.3, SD = 2.6) enrolled in the program and were matched with a medical student mentor. Feasibility and acceptability of the intervention was assessed through enrollment rates, reasons for refusal, retention rates, engagement with the intervention, satisfaction, and reasons for drop-out. Dependent t-tests were used to evaluate the preliminary effects of the intervention on patient transition readiness, health-related quality of life, self-efficacy, SCD knowledge, medication adherence, and health literacy. RESULTS: Participants (N = 24) demonstrated adequate retention (75.0%), adherence to the intervention (M = 5.3 of 6 sessions), and satisfaction with the intervention components. Participants demonstrated significant improvements in transition readiness (p = .001), self-efficacy (p = .002), medication adherence (p = .02), and health literacy (p = .05). CONCLUSIONS: A medical student mentor intervention to facilitate transition from pediatric to adult care for AYA with SCD is both feasible and acceptable to patients and medical students. Preliminary results suggest benefits for patients, warranting a larger efficacy study.