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Background: Depression and anxiety are associated with poor health-related quality of life (HRQoL), lower functioning and decreased treatment adherence. In 2019, 7% adults in the US had moderate/severe symptoms of depression, while Disclosures Roberts: Genentech, Novo Nordisk, Octapharma, Pfizer, Sanofi, Takeda, uniQure: Consultancy; Takeda; Speakers Bureau: Novo Nordisk, Octapharma, Sanofi, Takeda.: Research Funding. Kulkarni: Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire/Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sidonio: Bayer: Consultancy; Catalyst: Consultancy; Genentech: Consultancy, Research Funding; Novo Nordisk: Consultancy; Guardian Therapeutics: Consultancy; Octapharma: Consultancy, Research Funding; Biomarin: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Research Funding. Carpenter: Genentech: Honoraria; Novo Nordisk: Honoraria; Kedrion Pharmaceuticals: Honoraria; Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees. Konkle: Pfizer, Sangamo, Sanofi, Sigilon, Spark, Takeda and Uniqure: Research Funding; BioMarin, Pfizer and Sigilon: Consultancy. Wu: Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., Octapharma USA, Inc., Genentech Inc.: Research Funding. Curtis: Pfizer, Bayer, and Novo Nordisk: Consultancy; University of Southern California: Consultancy. Nichol: Pfizer, Genentech Inc., Baxalta US Inc., Bannockburn, IL (a Takeda Company), Octapharma, CSL Behring, Global Blood Therapeutics, and Novo Nordisk: Research Funding.

Randall Curtis,1 Marilyn Manco-Johnson,2 Barbara A Konkle,3 Roshni Kulkarni,4 Joanne Wu,5 Judith R Baker,6 Megan Ullman,7 Duc Quang Tran Jr,8 Michael B Nichol5 1Factor VIII Computing, Berkeley, CA, USA; 2Hemophilia and Thrombosis Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 3Washington Center for Bleeding Disorders, BloodWorks Northwest and the University of Washington, Seattle, WA, USA; 4MSU Center of Bleeding and Clotting Disorders, Department Pediatrics and Human Development, Michigan State University, East Lansing, MI, USA; 5Sol Price School of Public Policy, University of Southern California, Los Angeles, CA, USA; 6Public Health Department, The Center for Comprehensive Care & Diagnosis of Inherited Blood Disorders, Orange, CA, USA; 7Department of Pediatrics, Gulf States Hemophilia & Thrombophilia Center, University of Texas Health Science Center at Houston, Houston, TX, USA; 8Department of Hematology and Medical Oncology, Hemophilia of Georgia Center for Bleeding & Clotting Disorders of Emory, Emory University School of Medicine, Atlanta, GA, USACorrespondence: Michael B Nichol, Sol Price School of Public Policy University of Southern California, 650 Childs Way, RGL 212, Los Angeles, CA, 90089, USA, Tel +1 213 740 2355, Fax +1 213 740 3460, Email mnichol@usc.eduPurpose: We compare the impact of hemophilia on comorbidities, joint problems, health-related quality of life (HRQoL) and health-care utilization between two age groups: 40– 49 years and ≥ 50 years.Patients and Methods: The HUGS VII study recruited persons with hemophilia A or B age ≥ 40 years. Participants completed surveys to collect data on sociodemographic and clinical characteristics, hemophilia treatment regimen, pain, joint problems, comorbidities, HRQoL, depression and anxiety, at baseline and 6-months later. Clinical chart reviews documented hemophilic severity and treatment.Results: The sample includes 69 males, 65.2% aged ≥ 50 years, 75.4% with hemophilia A. Individuals ≥ 50 years were more likely to have mild or moderate hemophilia (68.9% vs 41.7%, P = 0.03) than those 40– 49 years old. Among persons with mild/moderate hemophilia, those ≥ 50 years old reported a higher rate of joint pain (83.9% vs 70.0%, P = 0.34 at baseline, 91.3% vs 57.1%, P = 0.06 at follow up) or range of motion limitation (73.3% vs 60.0%, P = 0.43 at baseline, 73.9% vs 28.6%, P = 0.04 at follow up) than the younger group. Compared to the younger group, the older group reported fewer emergency room visits (4.5% vs 21.7%, P = 0.03), and physical therapy visits (15.9% vs 43.5%, P = 0.01) at baseline. The sample depression rate was 85.7%, but the differences among the age groups were not significant. The mean covariate-adjusted EQ-5D index score was lower in older persons (0.77 vs 0.89, P = 0.02).Conclusion: Older persons with hemophilia in this sample are over-represented by individuals with mild/moderate disease, potentially due to premature death among those with severe disease. Although this group included a larger proportion of individuals with mild disease than the younger group, they experienced lower quality of life, more comorbidities both of aging and of hemophilic arthropathy, and lower rates of health-care utilization.Keywords: hemophilia A, hemophilia B, burden of hemophilia, aging in hemophilia

Background: The Consensus Study report from National Academy of Science, Engineering, Medicine on September 2020 found a lack of data to characterize sickle cell disease (SCD) related disease burden, outcomes, and the unmet needs. This study’s objectives were to 1) assess the feasibility of collecting data to estimate illness burden in adults with SCD; 2) investigate factors associated with health-related quality of life (HRQoL); and 3) estimate the societal burden. Method: We recruited 32 adults aged ≥18 years with a diagnosis of SCD who obtained care at two adult SCD specialty centers in the US. We collected data on fatigue, HRQoL measured by the EQ-5D-3L and the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), and the Work Productivity and Activity Impairment via patient survey. Healthcare utilization was abstracted for the 12 months prior to enrollment using medical chart review. Factors associated with HRQoL scores were assessed by Pearson correlations. Results: Data collection was feasible, although prescription data could not be used to estimate medication costs. Mean age was 36.7±10.6 (standard deviation) years, 84.4% had hemoglobin (Hb)SS/Sbthal0 disease, and 81.3% reported chronic pain (experiencing pain on ≥3 days per week in the past 6 months). Mean EQ-5D VAS was 63.4. The mean EQ-5D index score was 0.79. ASCQ-Me scores are comparable to the referent population of adults with SCD. The mean fatigue score was 57.9 (range 33.7-75.9) and was negatively correlated with the EQ-5D index score (correlation coefficient r=-0.35, p=0.049), and ASCQ-Me scores, including pain (r=-0.47, p=0.006), sleep (r=-0.38, p=0.03), and emotion (r=-0.79, pConclusions: Fatigue, SCD complications, hospitalization and chronic pain negatively impact HRQoL in this small cohort of US adults with SCD. This sample experienced a high economic burden, largely from outpatient doctor visits.

Background Knowledge about sexual health, difficulty with sexual activity and intimacy (sexual difficulty), in people with hemophilia is little understood. Objectives The objectives were to determine the prevalence of sexual difficulty in people living with hemophilia (PWH) compared to people with no bleeding disorders (PWNoBD), and to determine factors associated with it. Methods This was an analysis of the PROBE study. We recruited individuals who had hemophilia A or B (PWH) and PWNoBD who were 18 years old or older. We calculated proportions of participants with sexual difficulty and odds ratios (ORs) adjusted for sex and age with 95% confidence intervals. Results There were 2007 PWH and 1972 PWNoBD. Mean (standard deviation) age was 41 (15) years in PWH and 42 (13) years in PWNoBD. Sexual difficulty was reported in 302 (15.1%) PWH and 79 (4.0%) PWNoBD. The odds of sexual difficulty were significantly higher in PWH (OR 3.82, 95% CI 2.85, 5.11). Among PWH, older age, experiencing acute or chronic pain in the past 12 months, bleeds within the past two weeks, ≥3 spontaneous joint bleeds (past six months), limitation of range of motion of any joints, and any life- or limb-threatening bleeds in the past 12 months were associated with sexual difficulty. Conclusions Sexual difficulty is more prevalent in people living with hemophilia and associated with markers of disease severity. Sexual health issues should be incorporated in comprehensive hemophilia care, future research, and hemophilia related health policy.

Introduction There are limited data on the impact of haemophilia on health status and health-related quality of life (HRQL) in people with non-severe (mild and moderate) haemophilia. Aim To evaluate the health status of people living with mild or moderate haemophilia. Methods Data on respondents with no bleeding disorder (NoBD), mild and moderate haemophilia patients were drawn from the PROBE study. Respondents were enrolled using network patient organizations. This analysis was performed as a cross-sectional study. Primary outcomes were reported bleeding, acute and chronic pain, activities of daily living and HRQL. Results A total of 862 respondents with NoBD (n = 173), mild (n = 102) and moderate (n = 134) haemophilia were eligible, with a median age of 33, 42 and 43, respectively. In relation to haemophilia-related sequalae, 53% of male and 29% of female patients with mild and 83% of males with moderate haemophilia had more than 2-3 bleeds in the last 12 months. Reporting of acute and chronic pain is less in those with NoBD compared to the mild and moderate cohorts for both genders. Multivariate analysis demonstrates significant reductions in quality of life using VAS, EQ-5D-5L and PROBE for males with mild and moderate haemophilia (P ≤ .001) with only PROBE indicating a significant reduction for females with mild (P = .002). Conclusion People affected by mild or moderate haemophilia report a significant HRQL impact due to haemophilia-related bleeding. Future research is needed to identify the optimal care management of patients with mild and moderate haemophilia.

Background The Patient Reported Outcomes, Burdens and Experiences (PROBE) study aims to develop and validate questionnaire for assessing health status in patients with haemophilia and participants without bleeding disorders. Objective To investigate the test-retest properties of the PROBE questionnaire. Methods The PROBE questionnaire covers four domains and is comprised of 29 questions. People with haemophilia (PWH) and participants without bleeding disorder were invited to participate in this study. All participants were asked to complete the PROBE questionnaire three times (paper-based survey on two consecutive days: T1 and T2 and then a web-based version: T3). Test-retest properties and percentage agreement were analysed. Results A total of 63 participants were enrolled in this study with a median age of 50 (range: 17-76) years. Of these, 30 (47.6%) were PWH. On the questions common to PWH and participants without bleeding disorder, Kappa coefficients ranged from 0.69 to 1.00, indicating substantial to almost perfect agreement (T1 vs T2). For haemophilia-related questions (T1 vs T2), Kappa coefficients ranged from 0.5 to 1.0. Of these, 5 of 11 items were in perfect agreement (Kappa = 1.0). The web-based questionnaire (T3) showed substantial to almost perfect agreement with the paper version (T1 test-retest properties were comparable between PWH and individuals without a bleeding disorder). Conclusions The results suggest that PROBE is a reliable tool to assess patient-reported outcomes for PWH and benchmark data in participants without bleeding disorder. The web-based questionnaire and the standard paper-based version can be used interchangeably.

Aim: The recommended low-density lipoprotein cholesterol (LDL-C) levels of the guideline may be appropriate for Caucasian patients but not for other ethnic groups. Methods: A cohort study was conducted in Hong Kong, and acute coronary syndrome (ACS) patients who received percutaneous coronary intervention (PCI) between 2005 and 2015 were enrolled. The primary outcomes of interest were the total cost of care and cardiovascular-related cost during one-year follow-up. The cost difference by lipid goal attainments was analyzed by Poisson regression with multivariate treatment effects. The clinical outcomes achieved by lipid goal attainments in terms of major adverse cardiovascular events were analyzed by multivariate Cox regression. Results: Among the 4638 patients, 79.50%, 48.64%, and 36.14% attained the LDL-C goals of < 2.6, < 2.0, and < 1.8 mmol/L for one year, respectively. Only about 16% patients achieved the ≥ 50% reduction from baseline. None of these lipid goals was associated with a significant reduction in the total cost of care. We only identified the clinical benefits associated with the lipid goal of < 2.6 mmol/L. Other more stringent lipid goals seemed to bring a significant economic burden on cardiovascular-related cost, but their clinical benefits were uncertain. Conclusions: Lowering LDL-C to achieve the guideline-recommended target levels for post-PCI ACS patients may lead to fewer cardiovascular events, but it may not necessarily lead to economic benefits within one year of follow-up.

We estimate multiple treatment effects in presence of selection-bias and response heterogeneity, using panel data. A control function was added to a fixed-effects based correlated random coefficients model. Selection model to create the control function was contrasted between multinomial logit and multinomial probit. For the multinomial logit model, parametric and semi-parametric bias correction techniques, as proposed in Lee (Econometrica 51(2):507–512, 1983), Dubin and McFadden (Econometrica 52(2):345–362, 1984) and Dahl (Econometrica 70(6):2367–2420, 2002) respectively, were implemented. We find that controlling time-varying endogeneity, allowing response heterogeneity, the type of bias correction method and the choice of the selection model, each had significant impact on the estimated treatment effects. Using the case of biologic DMARDs, we show that in the presence of heterogeneity and multiple treatments, the specification of the latent index model should be carefully chosen along with selection bias correction techniques appropriate to the choice of the latent index model. These issues have an important impact on policy. Under one set of assumptions, we may accept a formulary expansion policy on biologic DMARDs to be cost-neutral, while rejecting the same policy as not cost-saving under another set of assumptions.

Background The interest of health care agencies, private payers and policy makers for patient-reported outcomes (PRO) is continuously increasing. There is a substantial need to improve capacity to collect and interpret relevant PRO data to support implementation of patient-centered research and optimal care in haemophilia. The Patient Reported Outcomes, Burdens and Experiences (PROBE) Project aims to develop a patient-led research network, to develop a standardized questionnaire to gather patient-reported outcomes and to perform a feasibility study of implementing the PROBE questionnaire. Methods A pilot questionnaire was developed using focus group methodology. Content and face validity were assessed by a pool of persons living with haemophilia (PWH) and content experts through interactive workshops. The PROBE questionnaire was translated with the forward-backward approach. PROBE recruited national haemophilia patient non-governmental organizations (NGOs) to administer the questionnaire to people with and without haemophilia. PROBE measured the time to complete the questionnaire and gathered feedback on its content and clarity; staff time and cost required to implement the questionnaire were also collected. Results The PROBE questionnaire is comprised of four major sections (demographic data, general health problems, haemophilia-related health problems and health-related quality of life using EQ-5D-5L and EQ-VAS). Seventeen NGOs participated in the pilot study of the PROBE Project, recruiting 656 participants. Of these, 71% completed the questionnaire within 15 min, and all participants completed within 30 min. The median total staff and volunteer time required for the NGOs to carry out the study within their country was 9 h (range 2 to 40 h). NGO costs ranged from $22.00 to $543.00 USD per country, with printing and postage being the most commonly reported expenditures. Conclusions The PROBE questionnaire assesses patient-important reported outcomes in PWH and control participants, with a demonstrated short completion time. PROBE proved the feasibility to engage diverse patient communities in the structured generation of real-world outcome research at all stages. Trial registration Trial registration: NCT02439710. Electronic supplementary material The online version of this article (10.1186/s40814-018-0253-0) contains supplementary material, which is available to authorized users.

Introduction: Over the past 21 years, treatment options for hemophilia have evolved significantly. The objective of this study is to describe the trends observed in clinician prescribing practices for management of hemophilia A (HA) and B (HB) in the United States (US) via three surveys from 1999-2021. Methods: We administered surveys to members of the Hemostasis & Thrombosis Research Society (HTRS) via an in-person paper survey at its annual symposia in 1999 and 2015, and an online survey in 2021. The survey participants included physicians, physician assistants, and nurse practitioners who manage the care of hemophilia patients at hemophilia treatment centers in the US. The surveys collected information regarding: 1) characteristics of clinician practice, 2) prescribed clotting factor products and dosages used for routine bleeds or major life-threatening bleeding, total joint replacement, and port placement, 3) reasons for changing doses, 4) frequency of recommendation for prophylaxis and inhibitor treatment for associated factor and non-factor products, and 5) gene therapy. Results: Forty-one clinicians completed the survey in 1999 and 2021, 53 in 2015. The mean number of patients seen by respondents increased from 142 (range: 0-314) for children and 101 (0-480) for adults in 1999 to 202 (0-900) for children and 154 (0-500) for adults in 2021. The proportion of clinicians prescribing >40 units/kg of Standard Half Life (SHL) Factor IX concentrates for routine bleeding events in HB patients increased from 22.5% in 1999 to 50.9% in 2015, and 87.8% in 2021. The proportion of clinicians reported SHL Factor VIII usage for routine bleeding at a dose of >40 units/kg in HA patients increased from none in 1999 to 11.3% in 2015 and 29.3 % in 2021. The reported rates of prescribing an average >60 units/kg factor to treat major life-threatening bleeds increased from 67.5% in 1999 to 90.3% in 2021 for HB; rates were 2.5% in 1999, 17.3% in 2015 and 7.3% in 2021 for treating HA. For children 91% of clinicians reported prescribing emicizumab to treat HA inhibitors in patients of all ages, while >87% reported prescribing it to treat HA without inhibitor. Clinicians were more likely to always prescribe emicizumab to treat HA patients with inhibitors (63.2% for children and 57.1% for adults), as compared to always prescribing it for those without inhibitors (13.2% for children and 5.7% for adults). The most frequent reported method to treat a patient with a history of inhibitors on emicizumab who had break through bleeds was rFVIIa: 85.4% for children, and 75.6% for adults. The most frequently reported reasons for switching from FVIII to emicizumab were fewer injections/visits (87.8%), and improved patient quality of life (82.9%). Thirty-nine percent of clinicians reported caring for patients currently in gene therapy trials, 27.5% had patients who had completed gene therapy. When asked about potential future prescribing practices, 14.6% reported that they would prescribe gene therapy "all the time", 4.9% would prescribe it "about 3/4 of the time", 29.3% "about 1/2 the time", 29.3% "about 1/4 the time", and 22.0% "rarely or never". Conclusion: These data indicate changes in prescribing practices among hemophilia specialists in the US over the past 21 years. Prescribing of high doses of factor (>40 units/kg) increased, while ITI prescribing practices remained similar over time. To treat patients with major life-threatening bleeds, a larger proportion of clinicians prescribed high doses of factor (>60 units/kg) for patients with HB as compared to HA. Most clinicians frequently prescribed emicizumab for patients with HA inhibitors, but less frequently for those without inhibitors. At this time, there is wide diversity among clinicians in the expected uptake of gene therapy. Disclosures Curtis: Pfizer, Bayer, and Novo Nordisk: Consultancy; University of Southern California: Consultancy. Roberts: Takeda; Speakers Bureau: Novo Nordisk, Octapharma, Sanofi, Takeda.: Research Funding; Genentech, Novo Nordisk, Octapharma, Pfizer, Sanofi, Takeda, uniQure: Consultancy. Decker-Palmer: Genentech Inc. --A member of the Roche Group.: Current Employment, Current equity holder in publicly-traded company. Khairnar: Genentech Inc - A Member of The Roche Group: Current Employment; University of Maryland, Baltimore: Ended employment in the past 24 months; Roche: Current equity holder in publicly-traded company. Wu: Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., Octapharma USA, Inc., Genentech Inc.: Research Funding. Nichol: Pfizer, Genentech Inc., Baxalta US Inc., Bannockburn, IL (a Takeda Company), Octapharma, CSL Behring, Global Blood Therapeutics, and Novo Nordisk: Research Funding.

Introduction: Persons with hemophilia suffer from recurrent bleeds, especially hemarthrosis, which results in joint damage. Hemophilia inhibitor status impacts bleeding, which is associated with acute and chronic pain. To better characterize the impact of inhibitor status, we compared patient-reported outcomes (bleed rate, pain, and joint health), work productivity and activity impairment (WPAI), and health-related quality of life (HRQoL) by inhibitor status, and investigated the correlation of patient-reported outcomes with WPAI and HRQoL. Methods: The U.S. Hematology Utilization Group Studies Part VIII prospectively collected data to examine the cost and burden of hemophilia in persons with hemophilia A (PwHA) aged ≥2 years obtaining care at four federally-supported hemophilia treatment centers. From April 2019 to May 2021 we enrolled PwHA with and without inhibitors at a 1:2 ratio. Parents/adult participants completed a survey at enrollment to collect sociodemographic and clinical characteristics, self-reported bleeds in the last month, pain, and joint stiffness (5-item scale). We also measured WPAI and HRQoL using EQ-5D-3L. Clinical chart review documented hemophilic severity, inhibitor level and treatment regimen. Participants were classified into three groups: 1) active inhibitor (inhibitor titer ≥1.0 Bethesda Units (BU) six months prior to enrollment), 2) tolerized inhibitor (history of inhibitor titer ≥1.0 BU, immune tolerance induction (ITI) and/or currently using factor VIII for prophylaxis), and 3) no inhibitor. Patient-reported data were compared across these groups using Chi-square tests for categorical variables and generalized linear models for continuous variables. Association of bleeds, pain, and joint stiffness with HRQoL and WPAI were assessed using Pearson correlation. Results: Among 80 PwHA enrolled, 9 (11%) had active inhibitors, 22 (27.5%) had tolerized inhibitors, and 49 (61.3%) had no inhibitors. Mean age was 24.9±14.3 (standard deviation) years, 66.3% were adults, 87.5% had severe hemophilia, and 87.5% used prophylaxis. Mean age of the non-inhibitor group (29.3±13.5) was older than the tolerized inhibitor group (16.3±9.5 years, p0.05). The non-inhibitor group had a lower rate of severe hemophilia (81.6%) or prophylactic treatment (81.6%) than those in the active (100%) or tolerized groups (95.5%, p=0.13). Larger proportions of participants with active inhibitors (66.7%) and no inhibitors (57.1%) reported having bleeds in the last month compared to those with tolerized inhibitors (22.7%, p=0.01). Participants without inhibitors had a greater mean number of bleeding episodes (1.09±standard error (SE) 0.26 vs. 0.23±0.38, p=0.03), specifically joint bleeds (0.58±0.16 vs. 0.08±0.24, p=0.03,) than the tolerized group. Those with active inhibitors reported significantly higher mean joint stiffness scores (35.1±2.6 vs. 27.5±1.9, p=0.006) or more joint pain (77.8% vs. 54.5%, p=0.23) than the tolerized group. Mean EQ-5D index score was significantly lower in the active inhibitor group (0.79±SE (0.07) than in the tolerized group (0.96±0.05, p=0.03). Joint bleeding, chronic pain, and joint stiffness were negatively correlated with the EQ-5D visual analogue scale, and index scores (all correlation coefficients |r|>0.43, all p Conclusions: This study is limited to a small sample skewed toward a younger age in the tolerized inhibitor group. PwHA in the active and no inhibitor groups experienced greater clinical burden as measured by bleeds compared to the tolerized group. Those with active inhibitor displayed lower HRQoL scores than the tolerized inhibitor group. Bleeds, chronic pain and joint stiffness were inversely correlated with HRQoL, resulting in lower work productivity and activity. Figure 1 Figure 1. Disclosures Roberts: Takeda; Speakers Bureau: Novo Nordisk, Octapharma, Sanofi, Takeda.: Research Funding; Genentech, Novo Nordisk, Octapharma, Pfizer, Sanofi, Takeda, uniQure: Consultancy. Khairnar: University of Maryland, Baltimore: Ended employment in the past 24 months; Roche: Current equity holder in publicly-traded company; Genentech Inc - A Member of The Roche Group: Current Employment. Decker-Palmer: Genentech Inc. --A member of the Roche Group.: Current Employment, Current equity holder in publicly-traded company. Curtis: Pfizer, Bayer, and Novo Nordisk: Consultancy; University of Southern California: Consultancy. Wu: Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., Octapharma USA, Inc., Genentech Inc.: Research Funding. Nichol: Pfizer, Genentech Inc., Baxalta US Inc., Bannockburn, IL (a Takeda Company), Octapharma, CSL Behring, Global Blood Therapeutics, and Novo Nordisk: Research Funding.

To determine US societal burden of illness, including direct and indirect costs and annual bleed rate (ABR), for persons with hemophilia B (HB), a rare and debilitating genetic disorder, and to examine associations of hemophilia severity and treatment regimens with costs and ABR.From 2009 to 2014, the Hemophilia Utilization Group Studies Part Vb collected prospective data from 10 US hemophilia treatment centers. Participants with HB completed initial surveys on sociodemographic characteristics, clinical characteristics, and treatment patterns. During the 2-year follow-up, participants reported bleeding episodes, work absenteeism, and caregiver time quarterly. These data were used to calculate ABR and indirect costs. Direct costs were calculated using 1-year clinical chart records and 2-year dispensing records.Of the 148 participants, 112 with complete medical records and one or more follow-up survey were included. Total mean annual per-person costs were $85,852 (median $20,160) for mild/moderate HB, $198,733 (median $147,891) for severe HB, and $140,240 (median $63,617) for all participants without inhibitors (P0.0001). Mean ABR for participants with severe HB on prophylaxis (5.5 ± 7.9 bleeds/y) was almost half that of those treated episodically. Clotting factor and indirect costs accounted for 85% and 9% of total costs, respectively. Compared with episodic treatment, prophylaxis use was associated with 2.5-fold higher clotting factor costs (P0.01), low but significantly more missed parental workdays (P0.0001) and clinician (P0.001) or nursing visits (P0.0001), less part-time employment and unemployment, and lower hospitalizations costs (P = 0.17) and ABR (P0.0001).HB is associated with high economic burden, primarily because of clotting factor costs. Nevertheless, prophylaxis treatment leads to clinical benefits and may reduce other nonfactor costs.

Background: von Willebrand disease (VWD) is the most common inherited bleeding disorder. Questions remain regarding the impact of VWD related bleeding phenotype on healthcare utilization, joint health, and health-related quality of life (HRQoL) in the US. Objective: Our study investigated the impact of VWD bleeding phenotype on healthcare utilization, joint health, and HRQoL in a geographically diverse cohort of individuals with VWD who obtain care at seven US Hemophilia Treatment Centers (HTCs). Methods: Hematology Utilization Group Studies (HUGS) prospectively examined the cost and burden of illness in persons with VWD. The current study enrolled individuals age ≥12 with VWD Type 1 (VWF:Ag/RCo: ≤30%), low VWF (VWF:Ag/RCo: 30-50%), Type 2, and 3. Participants completed a standardized interview to collect sociodemographic and clinical data, self-reported healthcare utilization and bleeding in last 6 months, self-reported pain, joint health and HRQoL measured by EQ-5D-3L. Clinical chart reviews abstracted information about VWD type and treatment. Association of bleeding and VWD type with healthcare utilization, joint health, and HRQoL were assessed using Chi-square or Fisher exact tests for categorical variables and Student T-tests or one-way ANOVA for continuous variables. P value ≥0.05 indicates not statistically significant (NS). Results: We analyzed 100 participants with complete baseline information. Mean age was 31.7 (SD=18.6) years, 67.0% were adults ≥18 years, 80.0% were female, 67.7% had Type 1/low VWF, and 3.0% had Type 3 VWD. Mean age at VWD diagnosis was 13.6 (SD=13.0) years. Persons with low VWF were diagnosed and received VWD treatment at an older age (mean 19.2, SD=11.8; 19.4, SD=11.9 years for diagnosis and treatment respectively) than those with Type 1 (13.7, SD=12.7; 15.6, SD=13.7), or Types 2&3 (9.4, SD=12.9; 13.3, SD=16.6), p=0.03 and p=NS. As compared to individuals without bleeding in the previous 6 months, those reported bleeding had significantly higher rate of medical procedures related to treating bleeding events (42.5% vs. 13.3%, p=0.001), and overnight hospitalization (20.0% vs. 3.3%, p Conclusions: Our study demonstrates that persons with VWD who obtain care at US HTCs experience significant illness burden regardless of severity. Self-reported recent bleeding as expected was associated with increased healthcare utilization and negative impact on joint health and HRQoL. Bleeding phenotype was significantly associated with healthcare utilization differences. Delayed diagnosis and treatment for persons with low VWF may impact their HRQoL, and if confirmed in a larger sample size would underscore the fact that low VWF is not necessarily a mild disorder compared to other VWD subtypes. Disclosures Roberts: Octapharma: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Pfizer: Consultancy; Takeda: Consultancy, Research Funding, Speakers Bureau; uniQure: Consultancy. Kulkarni:Bioverativ/Sanofi, BPL, Genentech, Kedrion, Novo Nordisk, Octapharma, Pfizer, Takeda, Catalyst Bioscience Bayer: Membership on an entity's Board of Directors or advisory committees; Sanofi/ Bioverativ, Bayer, Biomarin, Shire/Takeda, Novo Nordisk, Freeline: Other: clinical trial research grants . Sidonio:Octapharma, Grifols, Takeda and Genentech: Research Funding; Bayer, Bioverativ/Sanofi, Novo Nordisk, Takeda, Uniqure, Biomarin, Octapharma, Catalyst, Grifols, Sigilon, Tremeau, Genentech/Roche: Consultancy. Carpenter:Kedrion: Honoraria; Novo Nordisk: Honoraria; Genentech, Inc.: Honoraria; American Thrombosis and Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Research Funding; Shire: Research Funding; Hemostasis & Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; American Academy of Pediatrics: Other: PREP Heme/Onc editorial board. Konkle:Sigilon: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BioMarin: Consultancy; Sanofi: Consultancy, Research Funding; Takeda: Research Funding; Uniquire: Research Funding; CSL Behring: Consultancy; Roche: Consultancy; Baxalta: Research Funding; Spark: Consultancy, Research Funding. Wu:Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., and Octapharma USA, Inc.: Research Funding. Curtis:USC Hemophilia Utilization Group Study (HUGS): Consultancy; Bayer: Consultancy; Novo Nordisk: Consultancy; Patient Reported Outcomes, Burdens and Experiences: Consultancy. Carrasco:Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., and Octapharma USA, Inc.: Research Funding. Tran:Novo Nordisk: Consultancy; Bioverativ: Consultancy; Takeda: Consultancy; Bayer: Consultancy. Nichol:Global Blood Therapeutics: Research Funding; Octapharma: Research Funding; CSL Behring: Research Funding; Pfizer: Research Funding; Baxalta US Inc., Bannockburn, IL (a Takeda Company): Research Funding; Genentech Inc.: Research Funding.

BACKGROUD Improved care and prophylactic factor replacement therapy have lengthened life expectancy for persons with hemophilia (PWH). These advancements have created a new hemophilia cohort of senior persons not seen since the previous human immunodeficiency viruses (HIV) years, and little is known about their age-related health outcomes. OBJECTIVES We describe the impact of hemophilia on comorbidities, joint problems, healthcare utilization and health related quality of life (HRQoL) from the HUGS VII baseline data. METHODS HUGS VII prospectively examines the cost and burden of hemophilia, including HRQoL, arthropathy, and economic impact in persons with hemophilia A or B age ≥ 40 years who obtained care from three US Hemophilia Treatment Centers. Participants completed a standardized interview to collect clinical and sociodemographic characteristics, hemophilia treatment regimen, pain, joint problems, comorbidities, and HRQoL using EQ-5D-3L. Clinical chart reviews documented hemophilic severity and treatment. Participants' characteristics were compared between two age groups: 40-49 years and ≥ 50 years using Chi-square tests for categorical variables and T-tests for continuous variables. RESULTS This analysis includes a total of 70 male with hemophilia, 64.3% aged ≥50 years, 75.7% with hemophilia A. Individuals ≥ 50 years had higher rates of being married or with a partner (71.11% vs. 56.0%, P=0.20), retired/not employed (66.7% vs. 28.0%, P=0.002), and having mild or moderate hemophilia (68.9% vs. 40.0%, P=0.02) than those 40-49 years old. Use of prophylaxis was similar among age groups in severe hemophilia but lower for older mild/moderate PWH. Among persons with mild/moderate hemophilia, those ≥ 50 years old reported a higher rate of joint pain (83.8% vs 70.0%, P=0.37) or range of motion limitation (73.3% vs, 60.0%, p=0.45) than the younger group, although the differences were not statistically significant. Compared to those 40-49 years old, individuals ≥ 50 years old reported fewer emergency room visits (4.6% vs. 20.8%, P=0.03), and physical therapy visits (16.0% vs. 41.7%, P=0.06). The older age group had significantly higher rates of self-reported myocardial infarction (11.6% vs. 0%, P=0.08) and diabetes (24.4% vs. 4.0%, P=0.03) than those 40-49 years. Self-reported comorbidities were measured by asking "Has a doctor ever told you that you have certain conditions?" The most frequently reported comorbidities were hepatitis C infection (75.7%, 79.3% of persons with infected hepatitis C had been treated and, 82.7% cleared the hepatitis C virus), hypertension (47.1%), depression (23.2%) and anxiety (21.7%). Mean covariates adjusted EQ-5D index score was lower in older persons (0.79 vs. 0.87, P=0.09). CONCLUSIONS Older PWH are over-represented by individuals with mild/moderate disease, potentially due to premature death among those with severe disease. Although this group included a larger proportion of mild disease than younger PWH, it presented prevalent comorbidities both of aging and of hemophilic arthropathy, despite lower rates of healthcare utilization and use of preventive therapies. Disclosures Curtis: USC Hemophilia Utilization Group Study (HUGS): Consultancy; Patient Reported Outcomes, Burdens and Experiences: Consultancy; Bayer: Consultancy; Novo Nordisk: Consultancy. Konkle:Pfizer: Consultancy, Research Funding; Roche: Consultancy; BioMarin: Consultancy; Sigilon: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Takeda: Research Funding; Uniquire: Research Funding; CSL Behring: Consultancy; Baxalta: Research Funding; Spark: Consultancy, Research Funding. Kulkarni:Sanofi/ Bioverativ, Bayer, Biomarin, Shire/Takeda, Novo Nordisk, Freeline: Other: clinical trial research grants ; Bioverativ/Sanofi, BPL, Genentech, Kedrion, Novo Nordisk, Octapharma, Pfizer, Takeda, Catalyst Bioscience Bayer: Membership on an entity's Board of Directors or advisory committees. Wu:Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., and Octapharma USA, Inc.: Research Funding. Tran:Takeda: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Bioverativ: Consultancy. Nichol:Global Blood Therapeutics: Research Funding; CSL Behring: Research Funding; Octapharma: Research Funding; Genentech Inc.: Research Funding; Baxalta US Inc., Bannockburn, IL (a Takeda Company): Research Funding; Pfizer: Research Funding.

To estimate longitudinal trends in prevalence and incidence rates of adult ADHD 2006–2009. Kaiser Permanente Southern California (KPSC) electronic medical records were analyzed to assess prevalence and incidence rates for adult ADHD. Trends over time were estimated and compared using three case definitions (ADHD diagnosis only [DX], ADHD DX and ≥2 FDA-approved ADHD prescriptions [DX + RX], and ADHD DX and ≥1 behavioral therapy visit [DX + BT]). Prevalence and incidence rates of adult ADHD. Prevalence ranged from 151 (DX + RX) to 312 (DX) cases per 100,000 members in 2006, increasing to 239 (DX + RX) and 415 (DX) cases in 2009. Prevalence based on DX + BT declined from 185 in 2006 to 94 cases per 100,000 in 2009. In 2006, incidence ranged from 15 (DX + BT) to 68 (DX) cases per 100,000 person-years. Incidence rates remained stable throughout the study period. Stratified analyses based on DX + RX revealed only slight variations by gender, but sharp differences by age, with younger adults demonstrating a higher prevalence overall as well as dramatic increases over the study period. Prevalence was highest among Caucasians, increasing substantially across all race groups over time. A limitation of this study is that incidence rates may not be representative of new cases if diagnoses existed prior to enrollment in KPSC. Similarly, prevalence rates may be affected if patients sought care outside of the health plan. Adult ADHD prevalence in this managed care organization appears low, but showed increasing prevalence and incidence rates over time.

ObjectivesThe objective was to explore the differences in medication use pattern of lipid-lowering drug (LLD) and antiplatelet agents among post-percutaneous coronary intervention patients with acute coronary syndrome aged DesignRetrospective study.SettingThis study used deidentified claims data from Clinformatics Data Mart database (OptumInsight, Eden Prairie, Minnesota, USA) and electronic health records from HK Hospital Authority Clinical Data Analysis and Reporting System database.ParticipantsWe used 1 year prescription records of LLDs and antiplatelet agents among 1013 USA patients and 270 HK Chinese patients in 2011–2013.Primary and secondary outcome measuresContinuity was investigated on the assumption that one defined daily dose represented 1 day treatment. Medication possession ratio method was used to evaluate the adherence. Multivariate-adjusted logistic regressions were constructed to compare the good continuity and adherence levels in the merged database with the cutoffs set at 80%, and Cox proportional hazard models were built using the time to discontinuation as the dependent variable, to assess the persistence level.ResultsHK Chinese patients were less adherent (67.41% vs 84.60%, adjusted odds ratio (AOR) for Americans over Chinese=2.23 (95% CI=1.60 to 3.12), pConclusionsWe seemed to find HK physicians tended to prescribe cheaper and lower doses of statins and antiplatelet agents when compared with the privately insured patients in the USA, though the adherence and persistence levels of HK patients with statins were relatively good.

INTRODUCTION Depression can impact quality of life, functioning, and treatment adherence. However, depression in persons with hemophilia A (PwHA) is not uniformly examined nationwide. We report on depression and treatment-related hemophilia symptoms and utilization in a sample from six geographically representative U.S. Hemophilia Treatment Centers (HTCs). METHODS Hematology Utilization Group Studies part Va (HUGS Va, 2005-2007) was an observational study that collected data on sociodemographics and 12-Item Short Form Health Survey (SF-12) via patient survey, and clinical characteristics via medical chart review for adults (≥18 years old) with hemophilia A. Depressive disorders were assessed by the SF-12 mental component score (MCS), a validated population-based measure including depressive disorders. MCS≤45 has been identified as a depressive symptom threshold suggestive of a disorder. MCS≤36 indicate more severe psychological symptomatology and/or impairment. Demographic and clinical characteristic associations with depression were assessed using Chi-square tests. RESULTS The analysis included 147 adults with mean age 33.0±12.5 years old, 64% with severe hemophilia. Using the criteria of MCS≤45, 27.9% of sample had depressive disorder, and 10.2% had more severe depression at MCS≤36, higher than the 9.0% prevalence of current depression in the general U.S. population studied by CDC's Behavioral Risk Factor Surveillance System survey data (2006 and 2008). Compared with individuals with no depressive disorder, those with depression were less likely to complete their high school education (51.2% vs. 75.2%, P CONCLUSIONS This sample of PwHA reported higher rates of potentially depressive disorders than the general USA population. Lower educational levels, joint problems, and barriers to accessing care may be high-risk factors for depressive disorders. Disclosures Wu: Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., and Octapharma USA, Inc.: Research Funding. Curtis:USC Hemophilia Utilization Group Study (HUGS): Consultancy; Patient Reported Outcomes, Burdens and Experiences: Consultancy; Bayer: Consultancy; Novo Nordisk: Consultancy. Tran:Bayer: Consultancy; Takeda: Consultancy; Bioverativ: Consultancy; Novo Nordisk: Consultancy. Nichol:Octapharma: Research Funding; CSL Behring: Research Funding; Baxalta US Inc., Bannockburn, IL (a Takeda Company): Research Funding; Genentech Inc.: Research Funding; Pfizer: Research Funding; Global Blood Therapeutics: Research Funding.

BACKGROUND The Patient Reported Outcomes Burdens and Experience (PROBE) study has developed and validated the PROBE questionnaire for assessing patient-reported outcomes in people with haemophilia and participants without bleeding disorders. OBJECTIVE To explore the regional variations in the international implementation of the PROBE questionnaire. METHODS Data were collected from participants in four regions (Western Pacific, South America, North America and Europe). Participants were able to choose English or translated versions of the PROBE questionnaire into their first language. We used analysis of variance methods and multivariable regression to determine the relative contribution of the variance explained by region controlling for haemophilia diagnosis, age group and levels of educations. We also explored interactions between region and the other components. RESULTS We used 862 questionnaires from 14 countries. Mean age of participants was 40.03 years (standard deviation 13.89), and 73.67% were male. After adjusting, region contributed 0.44%-7.98% of the variance component in subitem scores and 0.26% in the PROBE score. Years of education contributed 0.34% in the PROBE score. Age and haemophilia diagnosis contributed 3.42% and 22.42% of the PROBE score. CONCLUSIONS The results demonstrate that the PROBE questionnaire is valid to implement for assessing health status among patients with haemophilia and participants without bleeding disorders across regions.

Improvements in hemophilia care over the last several decades might lead to expectations of a near-normal quality of life for young adults with hemophilia. However, few published reports specifically examine health status indicators in this population. To remedy this knowledge gap, we examined the impact of hemophilia on physical and social functioning and quality of life among a national US cohort of 141 young men with hemophilia aged 18-34 years of age who received care at 10 geographically diverse, federally funded hemophilia treatment centers in 11 states between 2005 and 2013 and enrolled in the Hemophilia Utilization Group Studies. Indicators studied included educational achievement, employment status, insurance, health-related quality of life, and prevalence of the following comorbidities: pain, range of motion limitation, overweight/obesity, and viral status. The cohort was analyzed to compare those aged 18-24 to those aged 25-34 years. When compared to the general US adult population, this nationally representative cohort of young US adults with hemophilia experienced significant health and social burdens: more liver disease, joint damage, joint pain, and unemployment as well as lower high-school graduation rates. Nearly half were overweight or obese. Conversely, this cohort had higher levels of health insurance and equivalent mental health scores. While attention has typically focused on newborns, children, adolescents, and increasingly, on older persons with hemophilia, our findings suggest that a specific focus on young adults is warranted to determine the most effective interventions to improve health and functioning for this apparently vulnerable age group.

Allergy immunotherapy (AIT) is the only available treatment that alters the natural course of allergies and has possible disease-modifying effects. AIT is administered primarily via subcutaneous injection delivered in a physician's office. Few studies have been conducted in the United States or Canada to evaluate the costs of subcutaneous immunotherapy (SCIT).To (a) describe SCIT administration processes, resources, and costs and (b) characterize the patient population receiving SCIT.A multisite, prospective, observational time and motion study was conducted. Injection and wait times were collected by a third-party observer on 1 visit for each patient. Extract preparation processes were also observed. Site staff reported on treatment protocols, administrative time, supplies, and patient medical history. Patients responded to questionnaires on demographics, reasons for treatment, medication use, productivity, and travel time. Costs were estimated by applying unit costs to the time observations and the patient- and staff-reported data.A total of 670 SCIT patients were enrolled at 6 sites in the United States and 6 sites in Canada. Average age in the United States was 41 years (SD = 18) and 44 years (15) in Canada, with 10% of the patients aged ≥ 65 years. Annual incomes were over $100,000 for 40% of U.S. patients and 30% of Canadian patients. U.S. patients had over 4 times as many different allergens in their SCIT treatments as Canadian patients, with a mean of 18 versus 4. The most common reasons reported for starting SCIT was a "desire to cure allergies once and for all" (73%) and that "symptoms are not improved by allergy medications" (60%). Percentages of patients taking allergy medications in the 4 weeks prior to observation were 86% in the United States and 66% in Canada: antihistamines 75% United States, 54% Canada; inhaled corticosteroids 32% United States, 22% Canada. The predominant comorbidity was asthma, 43% United States, 24% Canada. Site protocols for build-up treatment phases were 1 to 2 injections per week for an average of 25 weeks (range 12-52). Maintenance phases were 1 injection every 3 to 4 weeks for an average of 4 years (range 2.5-5). Eight of the sites had total mean staff times per injection visit of 7 to 22 minutes; 1 site averaged fewer minutes, and 3 sites averaged more. Total direct medical costs were an average of $30 for Canadian patients per visit and $32 per visit for U.S. patients, half accounted for by the cost of the extract. Pre- and postinjection administrative tasks were the second largest driver of direct costs. Total injection visit-related time for patients, including round-trip travel time, averaged about 80 minutes per visit in the United States and in Canada.Analyses revealed substantial variation in SCIT regimens among sites, but the sites had commonalities in the injection process components. SCIT requires patient commitment to a long-term treatment regimen involving numerous clinic visits and resources for administration.

OBJECTIVE: Preliminary evidence suggests that elder abuse forensic centers improve victim welfare by increasing necessary prosecutions and conservatorships and reducing the recurrence of protective service referrals. Center team members gather information and make decisions designed to protect clients and their assets, yet the collective process of how these case reviews are conducted remains unexamined. The purpose of this study is to present a model describing the interprofessional approach of investigation and response to financial exploitation (FE), a frequent and complex type of abuse of vulnerable adults. METHODS: To develop an understanding of the case review process at the Los Angeles County Elder Abuse Forensic Center (Center), a quasi-Delphi field study approach was used involving direct observations of meetings, surveying team members, and review from the Center's Advisory Council. The goal of this iterative analysis was to understand the case review process for suspected FE in Los Angeles County. RESULTS: A process map of key forensic center elements was developed that may be useful for replication in other settings. The process map includes: (a) multidisciplinary data collection, (b) key decisions for consideration, and (c) strategic actions utilized by an interprofessional team focused on elder justice. DISCUSSION: Elder justice relies on a complex system of providers. Elder abuse forensic centers provide a process designed to efficiently address client safety, client welfare, and protection of assets. Study findings provide a process map that may help other communities replicate an established multidisciplinary team, one experienced with justice system outcomes designed to protect FE victims. Language: en

This study aimed to assess the effect of low-density lipoprotein cholesterol (LDL-C) goal attainments (of2.6mmol/L and1.8mmol/L) on first major adverse cardiovascular events (MACEs) for acute coronary syndrome (ACS) patients who underwent percutaneous coronary intervention (PCI).A retrospective cohort study was conducted using case reviews of post-PCI ACS patients at an acute public hospital in Hong Kong between January 2009 and August 2015. Patients were followed from the date of PCI procedure until the first documented MACE (including all-cause death, myocardial infarction, heart failure, documented unstable angina, revascularization, and stroke) or to the end of the first year. Kaplan-Meier estimates were used to evaluate the impact of LDL-C goal attainments prior to the event on event-free time.A total of 1684 patients were identified (79.0% males). At one-year endpoint, 658 (39.1%) attained the LDL-C goal of1.8mmol/L, 727 (43.2%) had the LDL-C level between 1.8mmol/L and 2.6mmol/L, and 299 (17.8%) had the LDL-C level≥2.6mmol/L. About 10% experienced a MACE within one year. After adjustment for other available risk factors, attainment of LDL-C goal2.6mmol/L was significantly associated with lower rates of MACEs during the one-year follow-up; and those who achieved the LDL-C level of 1.8mmol/L did not seem to carry any incremental clinical benefits.Among post-PCI ACS patients, we merely observed a high correlation between the lipid goal attainment of2.6mmol/L and MACEs through one-year follow-up, but not for the goal of1.8mmol/L.

Advocacy coalitions often play an important role in the state health policymaking process, yet little is known about their structure, composition, and behavior. In 2008, California became the first state to enact a menu labeling law. Using the advocacy coalition framework, we examine different facets of the coalitions involved in California's menu labeling policy debate. We use a qualitative research approach to identify coalition members and explore their expressed beliefs and policy arguments, resources, and strategies by analyzing legislative documents (n = 87) and newspaper articles (n = 78) produced between 1999 and 2009. Between 2003 and 2008, six menu labeling bills were introduced in the state's legislature. We found the issue received increasing media attention during this period. We identified two advocacy coalitions involved in the debate-a public health (PH) coalition and an industry coalition. State organizations acted as coalition leaders and participated for a longer duration than elected officials. The structure and composition of each coalition varied. PH coalition leadership and membership notably increased compared to the industry coalition. The PH coalition, led by nonprofit PH and health organizations, promoted a clear and consistent message around informed decision making. The industry coalition, led by a state restaurant association, responded with cost and implementation arguments. Each coalition used various resources and strategies to advance desired outcomes. PH coalition leaders were particularly effective at using resources and employing advocacy strategies, which included engaging state legislators as coalition members, using public opinion polls and information, and leveraging media resources to garner support. Policy precedence and a local policy push emerged as important policymaking strategies. Areas for future research on the state health policymaking process are discussed.

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%, P0.05). 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.

ObjectiveTo assess the psychometric properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire.MethodsThis study was a cross-sectional, multinational study. Participants were enrolled if they were more than 10 years old and people with haemophilia A or B or people without a bleeding disorder. Participants were invited through non-governmental patient organisations in 21 countries between 01/27/2016 and 02/23/2017. The following psychometric properties: missing data, floor and ceiling effects, exploratory factor analysis and internal consistency reliability were examined. A PROBE Score was derived and assessed for its convergent and known groups validity.ResultsThe study analysed the data on 916 participants with median age of 37.0 (IQR 27.0 to 48.0) years, 74.8% male. In the domain assessing patient-reported outcomes (PROs), more than 15% of participants presented a ceiling effect for all items but two, and a floor effect for one item. Factor analysis identified three factors explaining the majority of the variance. Cronbach’s alpha coefficient indicated good internal consistency reliability (0.84). PROBE items showed moderate to strong correlations with corresponding EuroQol five dimension 5-level instrument (EQ-5D-5L) domains. The PROBE Score has a strong correlation (r=0.67) with EQ-5D-5L utility index score. The PROBE Score has a known groups validity among various groups.ConclusionsThe results of this study suggest that PROBE is a valid questionnaire for evaluating PROs in people with haemophilia as well as control population. The known-group property of PROBE will allow its use in future clinical trials, longitudinal studies, health technology assessment studies, routine clinical care or registries. Additional studies are needed to test responsiveness and sensitivity to change.Trial registration numberNCT02439710; Results.

Improvements in hemophilia care over the last several decades might lead to expectations of a near-normal quality of life for young adults with hemophilia. However, few published reports specifically examine health status indicators in this population. To remedy this knowledge gap, we examined the impact of hemophilia on physical and social functioning and quality of life among a national US cohort of 141 young men with hemophilia aged 18-34 years of age who received care at 10 geographically diverse, federally funded hemophilia treatment centers in 11 states between 2005 and 2013 and enrolled in the Hemophilia Utilization Group Studies. Indicators studied included educational achievement, employment status, insurance, health-related quality of life, and prevalence of the following comorbidities: pain, range of motion limitation, overweight/obesity, and viral status. The cohort was analyzed to compare those aged 18-24 to those aged 25-34 years. When compared to the general US adult population, this nationally representative cohort of young US adults with hemophilia experienced significant health and social burdens: more liver disease, joint damage, joint pain, and unemployment as well as lower high-school graduation rates. Nearly half were overweight or obese. Conversely, this cohort had higher levels of health insurance and equivalent mental health scores. While attention has typically focused on newborns, children, adolescents, and increasingly, on older persons with hemophilia, our findings suggest that a specific focus on young adults is warranted to determine the most effective interventions to improve health and functioning for this apparently vulnerable age group.

To examine the direct and indirect costs of hemophilia care among persons with hemophilia A in the US.Observational data were obtained from HUGS-Va, a multi-center study from six federally supported hemophilia treatment centers (HTCs). Eligible individuals completed a standardized initial questionnaire and were followed regularly for 2 years to obtain information on work or school absenteeism, time spent arranging hemophilia care, and unpaid hemophilia-related support from caregivers. Data from 1-year healthcare utilization records and 2-year clotting factor dispensing records measured direct medical costs. Indirect costs were imputed using the human capital approach, which uses wages as a proxy measure of work time output.A total of 222 patients with complete data were included in the analysis. Two-thirds had severe hemophilia and the mean age was 21.1 years. The use of prophylaxis in severe hemophilia patients is associated with statistically significant reduction in the numbers of emergency department (ED) visits and bleeding episodes compared with those who were treated episodically. From the societal perspective, mild hemophilia costs $59,101 (median: $7519) annually per person, $84,363 (median: $61,837) for moderate hemophilia, $201,471 (median: $143,431) for severe hemophilia using episodic treatment, and $301,392 (median: $286,198) for severe hemophilia receiving prophylaxis. Clotting factor contributed from 54% of total costs in mild hemophilia to a maximum of 94% for patients with severe hemophilia receiving prophylaxis.Hemophilia is a costly disorder not only because of its high medical expenses, but also due to the high indirect costs incurred.

INTRODUCTION:The Patient Reported Outcomes Burdens and Experiences (PROBE) questionnaire was developed with direct patient involvement in questionnaire design, conduct and analysis using patient-centered outcomes to assess health status in patients with hemophilia (PWH). Phase 1 confirmed robustness of the methodology and feasibility. Phase 2a investigated individual test-retest reliability. Phase 2b will explore population level reproducibility.METHODS:PWH and non-PWH individuals who attended a hemophilia-related workshop were asked to complete the PROBE questionnaire 3 times (paper-based survey on 2 consecutive days and then a web-based version). Test-retest reliability was analyzed using the percentage agreement and Kappa statistic. Kappa coefficient interpretation .81-1.00 almost perfect, .61- .80 substantial; .41- .60 moderate; .21 -.40 fair; .00 -.20, slight; and < .00 poor agreement.RESULTS:Sixty-three participants from twenty-one countries were enrolled with a median age of 50 (range 14–76) years. Of these, thirty (47.6 percent) were PWH or carriers, thirty-three (52.5 percent) were participants with no known bleeding disorders. On general health domain, Kappa coefficients ranged from .69 to .92, indicating substantial to almost perfect agreement, for all items. Reliability of the web-based questionnaire showed moderate to substantial agreement for all except one item. For the hemophilia-related domain, Kappa coefficients ranged from .5-1.0. Of these, five of eleven items were in perfect agreement (Kappa = 1.0). Reliability of web-based questionnaire items were in substantial to almost perfect agreement. For overall health related quality of life, the EuroQol five dimensions questionnaire (EQ-5D) had Kappa coefficients of .62 to .92. Intraclass correlation coefficient of visual analog scale (VAS) was .90 (95 percent Confidence Interval, CI; .83-.94). Test-retest reliability was comparable between hemophilia patients and participants with no known bleed.CONCLUSIONS:Phase 2a demonstrated individual test-retest reliability and suggests PROBE is a reliable tool to assess Patient Reported Outcomes in PWH. The Web-based questionnaire has an acceptable agreement with the standard paper-based version in all domains. PROBE Phase 2b, to demonstrate reproducibility at the population level, is on-going. To date, 1,039 participants have been recruited from 10 countries.

Background: Patient Reported Outcomes Burdens and Experiences (PROBE) questionnaire was developed for assessing health status in patients with bleeding disorders, specifically, hemophilia. Phase I of PROBE study confirmed robustness of methodology and feasibility of the questionnaire. Objective: To investigate the test-retest reliability of PROBE questionnaire Methods: Patients and non-hemophilia individuals who attended an hemophilia related workshops were invited to participate in this study. All participants were asked to fill out a PROBE questionnaire for 3 times. The paper-based questionnaires were collected immediately after being filled out on day 1 and day 2. Participants were instructed to log into the website within 2 weeks and fill out the web-based questionnaire. Test-retest reliability was analyzed. Results: A total of 63 participants were enrolled in this study with a median age of 50 (range 14-76) years. Of these, 30 (47.6%) were hemophilia patients or carriers, 33 (52.5%) were participants with no known bleeding disorders. On general health domain, Kappa coefficients ranged from 0.69 to 0.90, indicating substantial to almost perfect agreement for all items. Reliability of web-based questionnaire showed moderate to substantial agreement for all except 1 item. For hemophilia related domain, Kappa coefficients ranged from 0.5-1.0. Of these, 5 of 11 items were in perfect agreement (Kappa=1.0). Reliability of web-based questionnaire were in substantial to almost perfect agreement. For overall health related quality of life, EQ-5D had Kappa coefficients of 0.62 to 0.89. Intraclass correlation coefficient of visual analog scale (VAS) was 0.90 (95% confidence interval; 0.83-0.94). Test-retest reliability was comparable between hemophilia patients and participants with no known bleeding disorders. Conclusions: The results suggest that PROBE is a reliable tool to assess patients reported outcomes for hemophiliacs. Test-retest reliability analysis showed that the agreement was comparable between two participant populations. This result suggests that PROBE tool may be used to collect and compare not only patient reported outcome in hemophilia, but to generate norm values in appropriate control population. The Web-based questionnaire has an acceptable agreement with the standard paper-based version. Disclosures No relevant conflicts of interest to declare.