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Background: Sickle cell disease (SCD) is a genetic disorder that causes significant medical and neurologic morbidity in children. Hydroxyurea (HU) is the primary medication used to prevent these complications. National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend offering HU to children as young as 9 months of age with SCD (HbSS or HbSB0 thalassemia) using a shared decision-making approach. Although HU has proven efficacious it remains underutilized and caregivers report that they are not always actively involved in the decision to initiate this therapy. Reasons for limited HU uptake likely include lack of clinician knowledge and training and negative caregiver perceptions. Thus, we developed the Engage-HU trial as a novel approach to address HU utilization barriers. A critical consideration for this trial was that SCD primarily affects individuals of African and Hispanic/Latino descent. In these minority populations, intervention trials are sometimes terminated early because of recruitment difficulties related to mistrust of research, caregiver burden, and transportation issues. As such, the Engage-HU trial design included best-practice strategies for recruiting people of color in research. This study describes these strategies, the initial recruitment plan, preliminary recruitment outcomes and strategies, and our procedural adaptations. Study Design and Methods: Engage-HU is a randomized control trial (NCT03442114) to assess how clinicians can engage caregivers in a shared discussion that considers their values and preferences and includes evidence that supports HU. Engage-HU compares two dissemination methods for clinicians to facilitate shared decision-making with caregivers of young children with SCD: 1) the American Society of Hematology Pocket Guide, and 2) the HU Shared-Decision Making (H-SDM) Toolkit. The study aims to recruit 174 caregivers and evaluate the effectiveness of the dissemination methods on patient-centered outcomes (caregiver confidence in decision-making and perceptions of experiencing shared decision-making) as well as HU uptake and child health outcomes. Eligible children are aged 0 to 5 years, candidates for HU, and their caregiver has not made a decision about HU in the past 3 months. The trial is being conducted at 9 sites in the United States and uses a stepped-wedge design. Data will be analyzed based on the intent-to-treat principle. All participants will remain in the arm of the study to which they were randomized, regardless of whether or not they receive the assigned dissemination method. The primary endpoints are caregiver decisional uncertainty and caregiver perception of shared decision-making measured using validated tools. Data will be analyzed using a linear mixed effects regression model with a robust variance estimator and maximum likelihood estimation with observations clustered within site. The Engage-HU trial includes adaptations to increase recruitment such as tailored messaging, a relational recruitment approach, streamlined data collection, and a Stakeholder Advisory Committee. However, even with these adaptations, the first 6-months of the trial yielded lower than anticipated recruitment. Rather than terminate the trial or accept low enrollment, the research team implemented a series of recruitment strategies to address barriers including helping to improve research coordinator knowledge of the study purpose and adjusting no-show and follow-up procedures (e.g., calls to families after missed appointments and reminder calls before appointments). Site clinicians and clinic staff were provided with additional training so they could give more context about Engage-HU to caregivers and the study principal investigator led monthly "all coordinator" calls to provide support by sharing updates and experiences about successful recruitment. Implementation of these strategies resulted in triple the number of enrollments over the next 7-months compared to the previous 6-months (Table 1). Our goal in sharing this information is to provide lessons learned that can be implemented in future trials with the systematically underserved SCD population. It is also anticipated that methods described here may also inform clinical approaches to better engage caregivers of young children around critical clinical conversations, such as initiating medications like HU. Disclosures King: Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bioline: Consultancy; RiverVest: Consultancy; Novimmune: Research Funding; Celgene: Consultancy; Tioma Therapuetics: Consultancy; Amphivena Therapeutics: Research Funding; WUGEN: Current equity holder in private company; Cell Works: Consultancy; Incyte: Consultancy. Smith-Whitley:Prime: Other: Education material; Celgene: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Neumayr:Emmaus: Consultancy; Bayer: Consultancy; CTD Holdings: Consultancy; Pfizer: Consultancy; ApoPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Micelle: Other: Site principal investigator; GBT: Other: Site principal investigator; PCORI: Other: site principal investigator; Novartis: Other: co-investigator; Bluebird Bio: Other: co-investigator; Sangamo Therapeutics: Other; Silarus: Other; Celgene: Other; La Jolla Pharmaceuticals: Other; Forma: Other; Imara: Other; National Heart, Lung, and Blood Institute: Other; Health Resources and Services Administration: Other; Centers for Disease Control and Prevention: Other; Seattle Children's Research: Other. Yates:Novartis: Research Funding. Thompson:Novartis: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Research Funding; BMS: Consultancy, Research Funding; Baxalta: Research Funding; Biomarin: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding.

Sickle cell disease (SCD) is the most common genetic condition in the world and disproportionately affects African Americans in families with lower household incomes. SCD is characterized by a variety of complications including episodes of severe pain, chronic anemia, and end-organ damage. Morbidity from SCD begins in infancy and increases in frequency and severity with age. Complications during childhood and adolescence, both critical learning periods for youth, substantially impact educational attainment and life outcomes. SCD-related hospitalizations are associated with social determinants of health, such as socioeconomic status (SES), depression, health literacy, and educational outcomes. In youth with SCD, family and neighborhood SES are predictors of pain level, pain frequency, and overall quality of life. In addition to the physiological impacts of SCD, individuals with SCD experience emotional and stress related effects of the disease that may impact daily quality of life and frequency and severity of pain. Studies have found that hospital admission frequency has limited or no impact on academic outcomes in youth with SCD. Few studies have explicitly examined the relationship between SCD-related pain and educational, socioeconomic, and mental health outcomes. This is a cross-sectional study of patient survey data from a single site in the Sickle Cell Disease Implementation Science Consortium (SCDIC). The primary objective was to identify a relationship between educational attainment, employment status, mental health, and the frequency, severity, or length of pain crises for individuals with SCD. Multivariate analysis was used to assess the impact of patients' educational attainment, employment status, annual household income (low = less than $25,000, high = $75,001 and above), and self-reported depression on the frequency, length, and severity of SCD-related pain. Our central hypothesis was that individuals with a history of depression, lower educational attainment, periods of unemployment, and lower incomes experience more frequent, more severe, and longer pain crises. A total of 307 participants were included. The mean age was 27.4 years (range 15 to 45), 58.3% were female, and 99% were African American. Sixty-two percent had Hgb SS, the most severe form of SCD. About half of all patients (50.5%) reported they take pain medication every day for SCD and majority were on some form of disease modification (64.2% on hydroxyurea (HU), 20.2% on chronic blood transfusion). Slightly less than half (48.9%) reported their highest level of education as a high school diploma or lower. Most were unemployed (15.3%), students (22.8%), or disabled (21.5%), and 59.2% reported an average annual household income less than $25,000. Univariate analysis revealed statistically significant associations between employment status as unemployed or disabled and frequency of pain (p < .001), employment status as unemployed or disabled and severity of pain (p < .001), and employment status as disabled and length of pain > 4 days. Relationships between depression and frequency and severity of pain were statistically significant at the p < .001 level, and between depression and length of pain > 1 week at the p < .01 level. Multivariate analysis revealed positive statistically significant relationships between depression and high pain frequency (p < .001), employment status as disabled and severe pain (p < .01), depression and severe pain (p < .01), and employment status as disabled and length of pain >4 days (p < .05), Table 1. Educational attainment did not demonstrate statistically significant relationships with pain outcomes. No variables demonstrated statistically significant relationships with length of pain > 1 week and length of pain > 2 weeks. The only significant association with pain outcomes was that HU users were less likely to take daily opioids. Individuals with SCD who are disabled or have a history of depression are more likely to report more severe and frequent pain. No relationship emerged between educational attainment and pain outcomes. As the results are limited to the cross-sectional design, we cannot make statements of causality. For now, we know that people with SCD and these risk factors need further study for interventions. We plan to further assess study participants across all eight SCDIC sites in the next phase of this work. Disclosures King: Bioline: Consultancy; Amphivena Therapeutics: Research Funding; Incyte: Consultancy; Cell Works: Consultancy; Celgene: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; RiverVest: Consultancy; Tioma Therapeutics (formerly Vasculox, Inc.):: Consultancy; WUGEN: Equity Ownership.

Introduction In the United States 36% of adults have limited health literacy, which is associated with poor health outcomes (Kutner et al. National Assessment of Adult Literacy.2006). Health literacy is defined as "the capacity to obtain, process and understand basic health information and services needed to make appropriate health decisions" (Nielsen-Bohlman et al. National Academies Press.2004). Health literacy is understudied in sickle cell disease (SCD), a genetic disease affecting a minority population in the United States. SCD Preventive treatment requires patient engagement, therefore health literacy is an important determinant of health outcomes in SCD. Previous studies reported Health literacy in adolescents with SCD is suboptimal (Perry et al. J Pediatr Nur.2017), but few studies have investigated factors influencing health literacy in this population. Health literacy can be impacted by many factors such as cognition, socioeconomic status, education level and gender. This study evaluated health literacy level and factors that influenced Health literacy in adolescents and adults with SCD. In addition, we assessed the relationship of health literacy level and Hydroxyurea therapy use, one of only two FDA-approved disease-modifying therapies for SCD. Methods This was a cross- sectional study of adolescents and adults with SCD performed at St. Jude Children's Research hospital and St. Louis Children's hospital. Adolescents and adults ages 15 to 45 years completed a health literacy assessment using the newest vital sign (NVS). NVS is a validated tool with 6 questions that tests reading, mathematics and comprehension based on a nutrition label (Weiss et al. Ann Fam Med.2005). Score of 0-1 suggests high likelihood of limited health literacy, 2-3 indicates possibility of limited health literacy and 4-6 almost always suggests adequate health literacy. Self-reported demographic information was collected such as educational level, household income, age, sex, race. Additionally, SCD genotypes and hydroxyurea utilization were confirmed through chart review. Results A random sample of 125 adolescents and adults with SCD was evaluated (Table 1): 34 (28.1%) had Hb SC or Hb Sβ+-thalassemia, 87(71.9%) had Hgb SS or Hgb Sβ0-thalassemia, and 4 participants had unknown or other genotypes. Limited health literacy was prevalent, only 40 (32%) of subjects had adequate literacy, median NVS score was 2 for all participants. Participants with Hgb SS/Hgb Sβ0-thalassemia were more likely to be on hydroxyurea (p Conclusion This study shows a low prevalence of adequate health literacy amongst adolescents and adults with SCD. Our data corroborate previous literature which has reported limited health literacy in this population as well adds granularity to the factors that may influence this suboptimal outcome. There was a statistically significant association between health literacy, income level and education level in adolescents and young adults with SCD. Further, health literacy was not significantly associated with sickle cell genotype or hydroxyurea use. This study highlights the social determinants of health and specific need to address health literacy in SCD patients. To optimize the care of adolescents and young adults with SCD, targeted multimodal interventions that are tailored to low health literacy levels should be employed to reduce morbidity and mortality in this vulnerable population. Disclosures Kang: MBIO: Other: St. Jude Children's Research Hospital has an existing exclusive license and ongoing partnership with Mustang Bio for the further clinical development and commercialization of this XSCID gene therapy. King:Amphivena Therapeutics: Research Funding; Bioline: Consultancy; Celgene: Consultancy; Cell Works: Consultancy; Incyte: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; RiverVest: Consultancy; Tioma Therapeutics (formerly Vasculox, Inc.):: Consultancy; WUGEN: Equity Ownership. Zhao:MBIO: Other: St. Jude Children's Research Hospital has an existing exclusive license and ongoing partnership with Mustang Bio for the further clinical development and commercialization of this XSCID gene therapy. Hankins:NHLBI: Research Funding; National Committee for Quality Assurance: Consultancy; Global Blood Therapeutics: Research Funding; NHLBI: Honoraria; ASPHO: Honoraria; LYNKS Foundation: Research Funding; Novartis: Research Funding; Bluebird Bio: Consultancy.

Background Sickle cell disease (SCD) is one of the most common genetic conditions worldwide. In the United States it affects over 100,000 people, primarily African Americans, with increasing prevalence. With the widespread implementation of prophylactic penicillin, pneumococcal vaccinations and the use of disease modifying therapies such as Hydroxyurea, survival amongst children with SCD has improved greatly. Nonetheless, the life expectancy for adults with SCD remains 20 years lower than African Americans without SCD. The adolescent and young adult period is well described as time of increased healthcare utilization, high morbidity and mortality for patients with SCD. As a result, increased efforts to understand and improve the transition from pediatric to adult care are ongoing. Previous literature has eluded to the importance of patients' disease specific knowledge in improving this transition. However, there is limited literature that examines knowledge gaps across multiple domains. The goal of this study was to use qualitative methods to understand the role of health knowledge in the successful transition from pediatric to adult care for patients with SCD. Methods Participants were recruited using a purposeful recruitment approach from a large hospital system and local community. Stratified qualitative focus groups with patients (ages 15-25 years with any genotype of SCD) and their parents; and providers who cared for SCD patients were held. Semi-structured interviews with emergency department (ED) providers were also conducted. An interview guide was developed that specifically addressed faciltators and barriers to essential healthcare and educational attainment for young adults with SCD. Using an inductive and emergent coding approach, field notes and transcripts were analyzed for themes/subthemes. A focused sub-analysis looking at health knowledge was then conducted. Transcripts were double-coded by trained coders, discrepancies were resolved by consensus. Results 62 participants (23 patients, 20 caregivers, 20 providers) completed a total of 11 focus groups (8 patient-caregiver dyad focus groups, 3 provider focus groups) and 5 semi-structured interviews with ED providers. Analysis showed knowledge gaps across four major domains: patients, caregivers, educators and in the occupational setting. Patients expressed the desire to know more about treatment options for SCD. They noted specific challenges with self-management as new symptoms of SCD developed in adolescence and disease management increased in complexity. Patients noted that increased disease education and earlier transition planning may be helpful to improve this gap. Caregivers noted challenges with supporting their loved ones during the transition period due to limited knowledge about disease complications and management as they age. Patients and caregivers noted that this was mediated by patient-provider communication. Patients expressed educators' lack of knowledge about SCD as a barrier in the school setting. Participants noted that the implementation of formalized educational plans as well as educating teachers improved their academic experiences. Similarly, participants expressed that the lack of understanding about SCD related disease complications was a barrier to success in the occupational setting. Conclusions Multi-level knowledge gaps exist when examining the transition from pediatric to adult care. This study supports previous literature that highlights the need for patient education to improve disease specific knowledge, health literacy and self-management for young adults transitioning to adult care. This data also suggests that educational interventions across multiple settings may optimize this process. Focused interventions designed to increase SCD specific knowledge amongst caregivers, educators and in the occupational setting represent a feasible and readily implementable point of impact to improve patient-provider communication and overall outcomes in adolescents and young adults with SCD. The successful transition from pediatric to adult care requires a multidisciplinary approach in which the onus is not simply on the patient, but all involved in the care of the patient. Closing knowledge gaps across multiple domains is essential in improving care, quality of life and educational attainment in this vulnerable population. Disclosures No relevant conflicts of interest to declare.

Higher Prevalence of Hydroxyurea Use Is Associated with Lower Hospitalization Rate in a Population of Children with Sickle Cell Disease Cecelia L. Calhoun, MD; Ryan Colvin, MPH; Sherry Lassa-Claxton, MS; Arti Verlekar MS; F. Sessions Cole, MD; Monica L. Hulbert, MD Background Individuals with sickle cell disease (SCD) treated with hydroxyurea (HU) in clinical trials have had fewer hospitalizations and vaso-occlusive pain episodes than those on placebo. Since 2014, HU has been recommended for all children with Hemoglobin SS/S-β0 thalassemia, and many SCD centers have increased HU utilization. The effect of expanded HU treatment on hospitalization rate has not been reported in a population of children clinically treated with HU. In a pediatric SCD center cohort, we tested the hypothesis that increasing prevalence of HU treatment was associated with reduced hospitalization rate per patient-year and in total hospitalizations. Methods PedsNet, a PCORI-funded clinical research initiative, was queried for all patients with inpatient or outpatient encounters for SCD at St. Louis Children's Hospital (SLCH) from 2010 through 2015. Data from patients with ICD-9 codes indicating any genotype of SCD were included. Patients were considered to be receiving HU when it was prescribed on 2 or more outpatient encounters. Exclusion criteria were lack of SCD diagnosis confirmation, lack of outpatient visits at SLCH, and presence of a significant unrelated medical condition. Patients were censored at their 21st birthday or date of hematopoietic stem cell transplant. Data generated at the adult hospital were excluded. All hospitalizations in the final cohort were included for analysis, regardless of diagnosis code. For comparisons, patients were grouped as having a severe genotype (SS, S-β0 thalassemia, SD) or less-severe genotype (SC, S-β+ thalassemia). Statistical analysis was performed using SAS 9.4. Logistic and Poisson regression were used to compare proportions and rates between groups, respectively. Generalized Estimating Equations were used to account for within patient correlation. Results The PedsNet query identified 646 patients. Sixty patients were excluded due to lack of SCD diagnosis, 78 due to lack of outpatient care, and 4 due to severe unrelated disease (3 with congenital disease/malformation, 1 with cancer), leaving 504 who met all inclusion criteria (51.6% male). Hematopoietic stem cell transplant was performed in 23 patients during the study period. Of patients with a severe genotype, 28 (20.1%) received HU in 2010 compared with 111 (65.6%) in 2015 (p Conclusions In this clinical cohort of children with SCD, increasing prevalence of HU treatment was associated with significantly fewer total hospitalizations and a lower hospitalization rate per patient-year. The constant hospitalization rate in the less-severe genotype group suggests that the reduction is attributable to HU, rather than to other changes in clinical practice affecting patients with all genotypes. Hospitalization rates were higher among HU-treated patients, suggesting that more symptomatic children remain more likely to receive HU despite published recommendations to treat all children with severe genotypes. Families and clinicians may be reluctant to initiate HU for primary prevention of pain and hospitalizations in asymptomatic children. Future work should examine HU effects on specific SCD complications and on costs of care. Family and clinician interventions are needed to promote HU utilization in targeted patient groups. Table. Table. Disclosures Hulbert: Pfizer, Inc.: Other: spouse employment.

Background: The transition from the pediatric setting to adult care is a challenge for many adolescents with chronic disease. Patients with sickle cell disease (SCD) represent a unique cohort as the timing of psychosocial development of adolescence often coincides with worsening end organ damage. Previously, we used the Adolescent Autonomy Checklist (AAC) modified to include SCD specific tasks that patients with SCD need to practice in order to transition to adult healthcare and independent living. This study sought to use the AAC to measure the effects of skill based educational handouts on improving self-management and transition readiness in adolescents with SCD. Methods: This was a single center, retrospective study approved by the Washington University Institutional Review Board. Inclusion criteria were patients with SCD, age 13-21 years, and completion of pre and post assessments. As standard care, patients from a pediatric hematology clinic completed the AAC-SCD. The AAC-SCD assesses skill level in twelve domains (Table). The tool includes 100 items, and users check "can do already" or "needs practice" for each item. After review with the coordinator, participants were given skill-based handouts based on up to five noted deficits. Patients completed the AAC-SCD at the subsequent clinic visit. In addition to baseline and follow up AAC-SCD data, medical and demographic data were collected via chart abstraction. All data were entered into SPSS for statistical analysis, including descriptives, paired sample T-tests, and bivariate Pearson's correlations. Results: A total of 61 patients completed baseline and follow up. Of those participants, 49.2% were female. The mean age was 15.4 (+ 2.2) years. The genotypic distribution was as follows: 67.2% HbSS, 19.7% HbSC, 3.3% HbS-beta-thal+ and 9.8% HbS-beta-thal0. The majority of patients received healthcare coverage via Medicaid (52.5%), private insurance (45.6%) and 1.6% had no insurance coverage. Twenty-five patients (42.0 %) had a history of stroke or silent cerebral infarct and 34 (55.7%) were currently taking or were previously prescribed hydroxyurea. Formal academic support (IEP or 504 Plan) was reported for 20 (32.8%) of patients. At baseline, patients needed the most help with skills in the kitchen, housekeeping, personal care and leisure. Statistically significant improvements (p< 0.05) occurred in skills related to laundry, housekeeping, healthcare, sexual development and living arrangements. Modest sized and statistically significant correlation between the receipt of the educational handouts and decreased number of items marked "needs help" occurred in the areas of money management (r=-0.27, p=0.044), vocational skills (r=-0.27, p=0.046;) and laundry (r=0.32, p=0.015). A post hoc analysis by age groups 13-15 (n= 34),16-18 (n=24) and 19-21 (n=3) showed a decreased amount of items marked "needs help" in the areas of sexual development for both 13-15 year olds (r=0.42, p=0.024) and 16-18 year olds (r=0.93, p=0.001) as well. Conclusion: Transition skills improved over time among adolescents with SCD. While we cannot say for certain if gains in knowledge occur with age as development progresses or if a formal transition program can be credited, providing educational materials on transition related skills within a clinic setting was associated with significant improvements in three of the domains. Our preliminary data offers insight into what skill deficits may be most amenable to educational interventions based on age group. As is the case with medical management, the development of a multimodal intervention is needed to prepare adolescents with SCD to transition to adult care and independent living. Clinic based education is a simple intervention that could be one component of future approaches to transition. Disclosures No relevant conflicts of interest to declare.