BACKGROUND: After a dramatic increase in prevalence over several decades, obesity has become a major public health crisis in the United States. Research to date has consistently demonstrated a correlation between obesity and higher medical costs for a variety of U.S. subpopulations and specific categories of care. However, by examining associations rather than causal effects, previous studies likely underestimated the effect of obesity on medical expenditures. OBJECTIVE:To estimate the causal effect of obesity on direct medical care costs at the national and state levels.

BACKGROUND: Obesity imposes a substantial economic burden on the United States. The short-term value of nonsurgical weight loss (WL) and nonsurgical sustained WL (i.e., WL not resulting from bariatric surgery) is poorly understood. OBJECTIVES:To assess short-term (1 year) effect of nonsurgical WL and sustained nonsurgical WL (i.e., approximately 2 years) on per-patient-per-month (PPPM) total allcause health care costs among adults with obesity in the United States.

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Background In patients with sickle cell disease (SCD), health-related quality of life (HRQoL) is worse than in the general population and comparable or worse than in patients with other chronic or painful diseases such as cystic fibrosis or cancer. Targeting SCD pathophysiology may significantly improve HRQoL in addition to clinical outcomes. In the ongoing phase 1/2 HGB-206 Study (NCT02140554), which evaluates the safety and efficacy of LentiGlobin for SCD (bb1111) gene therapy (GT), the most recently treated cohort of patients (Group C) have demonstrated improvements in laboratory assessments, including a trend toward normalization in key hemolysis markers and improvements in total hemoglobin values, and near resolution of vaso-occlusive crises and acute chest syndrome (ACS), suggesting a fundamental effect on sickle cell pathophysiology. Patient-reported HRQoL outcomes through 12 months post-treatment are presented here. Methods Patients (≥12 and ≤50 years of age) with SCD and history of stroke or severe vaso-occlusive events, including acute episodes of pain and ACS, were enrolled. CD34+ cells collected by plerixafor mobilization/apheresis were transduced with BB305 lentiviral vector. LentiGlobin was infused following myeloablative busulfan conditioning. In addition to laboratory and clinical assessments, patients were monitored for patient-reported outcomes (PROs) using the PRO Measurement Information System (PROMIS)-57. PROMIS-57 assesses HRQoL using collection of short forms containing 8 questions for each of the 7 PROMIS domains (Depression, Anxiety, Pain Interference, Fatigue, Sleep Disturbance, in which a lower score denotes improvement, and Physical Function, Satisfaction with Participation in Social Roles, in which a higher score denotes improvement) and a 0-10 Pain Intensity numeric rating scale (NRS). PROMIS-57 has been validated in patients with SCD. Data were analyzed for ten Group C patients who had at least 12 months of follow-up and had completed PROMIS-57 assessments as of March 3, 2020. For each domain, patients were stratified into 2 sub-groups based on baseline scores and population norm (i.e., baseline scores "better" than or near the population norm and baseline scores "worse" than the population norm). The stratification was built upon the premise that patients with baseline scores "better" or near the population norm would not be expected to improve. The US general population norm was 2.6 for Pain Intensity and a T-score of 50 for all other domains. The minimal clinically importance difference (2-point difference for pain intensity NRS and 5-point difference for other domains) was selected based on the PROMIS guidelines and literature. Results Patients who had baseline scores "worse" than the population norm reported improvements in all domains at Month 6, which were sustained through Month 12. These patients reported clinically meaningful improvement in 6/8 domains; mean T-scores at baseline and Month 12 were 6 and 2.4 for Pain Intensity (n=5); 63 and 48 for Pain Interference (n=7); 62 and 48 for Anxiety (n=3); 62 and 44 for Depression (n=4); 39 and 60 for Satisfaction with Social Roles (n=5); and 40 and 56 for Physical Function (n=4), respectively. Only 1 patient was included in the analysis of Fatigue and Sleep Disturbance domains, thereby limiting the conclusions in these 2 domains (Figure 1). Patients who had baseline scores that were "better" or near than the population norm reported clinically meaningful improvements in the Physical Function (n=6) and Fatigue domains (n=9); mean scores at baseline and Month 12 were 49 and 55 for Physical Function and 50 and 43 for Fatigue, respectively. Among patients in this sub-group, Pain Intensity (n=5) and Pain Interference (n=3) scores were stable from Month 6 through Month 12; there was no clinically meaningful change for the Anxiety (n=7) and Depression (n=6) domains, however, worsening was observed in the Satisfaction with Social Role (n=4) and Sleep Disturbance (n=9) domains (Figure 1). Summary LentiGlobin for SCD GT improved HRQoL in all domains of PROMIS-57 for patients whose baseline scores were "worse" than the population norm, including clinically meaningful improvements in all evaluable (6/8) domains. Larger sample sizes are required to clarify the impact of LentiGlobin for SCD for some PROMIS-57 domains. Disclosures Kanter: SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; bluebird bio, inc: Consultancy, Honoraria; Novartis: Consultancy; Sanofi: Consultancy; Medscape: Honoraria; Guidepoint Global: Honoraria; GLG: Honoraria. Kwiatkowski:Terumo Corp: Research Funding; Imara: Consultancy; Celgene: Consultancy; Agios: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Novartis: Research Funding; Sangamo: Research Funding; Apopharma: Research Funding; Bristol Myers Squibb: Consultancy. Chen:bluebird bio, Inc.: Consultancy. Gallagher:bluebird bio, Inc.: Current Employment, Other: Ownership Interest and Salary. Ding:bluebird bio, Inc.: Current Employment, Other: Salary. Goyal:bluebird bio, Inc.: Current Employment, Other: Ownership Interest and Salary. Paramore:bluebird bio, Inc.: Current Employment, Other: Ownership Interest and Salary. Thompson:bluebird bio, Inc.: Consultancy, Research Funding; BMS: Consultancy, Research Funding; CRISPR/Vertex: Research Funding; Baxalta: Research Funding; Biomarin: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Walters:AllCells, Inc: Consultancy; Veevo Biomedicine: Consultancy; Editas: Consultancy.

BACKGROUND There are limited longitudinal studies following up persons with hemophilia (PWH) in adherence to clotting factor treatment and health outcomes. The Hemophilia Utilization Group Studies part Va (HUGS Va) was a two-year observational study of persons with hemophilia A conducted from 2005-2007. Participants from HUGS Va were enrolled to the long-term follow-up study (HUGS LTS) in 2014. OBJECTIVES To compare participants' characteristics between baseline of HUGS Va and follow-up in LTS; and investigate the impacts of changes of participants' characteristics on annualized bleeding rates. METHODS We collected data on sociodemographic and clinical characteristics. Self-reported bleedings were obtained from periodic surveys for 2-years in HUGS Va, and a survey that asked bleedings in the past 6-month in HUGS LTS. Clotting factor dispensing records were collected prospectively for two years in HUGS Va, and retrospectively for six months prior to HUGS LTS enrollment. Annualized bleeding rates and factor dispensing (unit/kg body weight) were calculated. Adherence to factor treatment was determined by the ratio of dispensed clotting factor to clinical recommended factor usage. We classified age at baseline of HUGS Va into three groups: children (aged 2-11 years), adolescents (aged 12-20 years), and adults (aged ≥21 years). The characteristics of participants were compared among the three age groups using Chi-square tests for categorical variables and ANOVA for continuous variables for each study. Annualized factor dispensed and bleeding rates were compared between HUGS Va and HUGS LTS using paired T-tests. RESULTS A total of 74 persons participated in both HUGS Va and LTS with completed data to calculate annualized factor dispensed and bleeding rates were included to the analyses. The mean age was 17.8±11.4 years in HUGS Va, and 26.2±11.5 years in LTS, respectively. The sample had 43% of children, 22% adolescents, and 35% adults at baseline. All adolescents at baseline transitioned to young adults in LTS. Approximately 80% of participants were severe hemophilia. Adults (73%) were less likely to have an entire year of health insurance as compared to children (100%) or adolescents (93.8%, P<0.01) in HUGS Va. Health insurance status was not significantly different among age groups in LTS. In HUGS Va, children had the highest rate of prophylactic treatment (74%), adherence to factor treatment (62%), highest mean annualized factor dispensed (4724±4090 u/kg), lowest rate of self-reported moderate or severe joint pain (31%), and lowest mean annualized bleeding rate (4.2±4.7); while adults had the lowest rate of prophylactic treatment (31%), adherence (28%), lowest mean annualized factor dispensed (2084±1870 u/kg), highest rate of self-reported moderate or severe joint pain (73%), and highest mean annualized bleeding rate (11.9±9.3), all P<0.05 among age group comparisons for these variables. There were 18 (26%) people (22% children, 17% adolescents, and 61% adults) switching from episodic treatment to prophylactic treatment from HUGS Va to LTS; others remained on the same treatment regimens. Adolescents and adults increased in prophylactic treatment (63% to 80% for adolescents, 31% to 69% for adults, respectively), adherence (36% to 75%, 28% to 61%), and mean annualized factor dispensed (3206±2581 to 4931±2945 u/kg, 2084±1870 to 4612±2577 u/kg) from HUGS Va to LTS. Mean annualized bleeding rates were not statistically significant different between HUGS Va (7.3±8.4) and LTS (10.6±22.0, P>0.05). The bleeding rates were not significantly different among age groups in LTS (P=0.06). CONCLUSIONS Although current literature indicated that PWH in transition from childhood to adulthood maybe at high risk of adverse health outcomes due to poor management of their condition with diminishing influence from parents, adolescents showed a significant increase in prophylactic treatment, adherence to factor treatment, and annualized factor dispensed, which may be associated with unchanged annualized bleed rates after they transitioned to adulthood in this study. Adults had a larger increase in dispensed factors than adolescents. Prophylaxis and adherence to clotting factor treatment were associated with a lower bleeding rate. Our current analyses reinforce the importance of prophylaxis and adherence to factor treatment for decreasing bleedings in persons with hemophilia A. Disclosures Nichol: Bayer: Research Funding; CSL Behring: Research Funding; Bioverativ: Research Funding; Shire/Baxter: Research Funding; Pfizer: Research Funding; Novo Nordisk: Research Funding; Genentech: Research Funding. Curtis:Gilead: Honoraria; Pfizer: Research Funding; Novo Nordisk: Honoraria, Research Funding; Shire/Baxter: Research Funding; Bioverativ: Research Funding; National Hemophilia Foundation: Honoraria; CSL Behring: Research Funding; Bayer: Research Funding, Speakers Bureau; Genentech: Honoraria, Research Funding. Ding:Novo Nordisk: Employment; Bioverativ: Research Funding. Aliyev:Genentech: Research Funding. Lou:Bioverativ: Research Funding; Novo Nordisk: Research Funding; Genentech: Research Funding; Bayer: Research Funding; Pfizer: Research Funding; CSL Behring: Research Funding; Shire/Baxter: Research Funding. Ullman:Genentech: Research Funding. Tran:Bioverativ: Honoraria; Novo Nordisk: Honoraria; Bayer: Honoraria; Genentech: Research Funding. Baker:Genentech: Research Funding. Riske:Genentech: Research Funding. Wu:Pfizer: Research Funding; Genentech: Research Funding; Bioverativ: Research Funding; CSL Behring: Research Funding; Bayer: Research Funding; Shire/Baxter: Research Funding; Novo Nordisk: Research Funding.

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