Distress effects are widely examined in cross-sectional studies with less known about effects on future health. This review summarizes distress impacts on health among adults in prospective studies and describes available distress measurement tools. Four inter-disciplinary databases were searched. Effects of distress on mortality and other outcomes were reviewed and estimated in a meta-analysis. A total of 19 studies were assessed which incorporated 10 distress tools. Distress had a detrimental effect on health regardless of the population studied, distress tool used, and health outcome examined. There was an increased mortality risk among those reporting high versus low distress (pooled hazard ratio (95% confidence interval) = 1.29 (1.15–1.46)).

Introduction The Patient‐Reported Outcomes Measurement Information System (PROMIS) provides measures of health status that assess physical, mental and social well‐being from the patient perspective. PROMIS measures are used in clinical practice and research across various patient populations but are not yet validated among patients with haemophilia. Aim Evaluate the sensitivity of PROMIS to indicators of haemophilia clinical severity and compare PROMIS measures to those from other PRO instruments. Methods Male adults with haemophilia (n = 115) completed the PROMIS‐29 short form which includes 4 questions for each of 7 domains: depression, anxiety, ability to participate in social roles and activities, physical function, pain interference, fatigue and sleep disturbance. Participant responses for each domain were scored on a T‐score metric with a mean of 50 and a standard deviation of 10 based on the original PROMIS reference sample of US adults. Participants also completed other generic and haemophilia‐specific health‐related quality of life questionnaires. Results Participants who experienced higher pain and depression levels reported significantly worse health in every PROMIS domain compared with their peers. Those who had recently needed to use crutches, visit an emergency department or were currently unemployed or disabled also reported poor PROMIS scores on most domains. Construct validity was supported by correlations between PROMIS domain scores and domain scores reported using the EQ‐5D‐5L and Haem‐A‐QoL. Conclusion The PROMIS instrument provides a potentially valuable tool to evaluate the impact of haemophilia and suggests usefulness in research and clinical practice.

Introduction: In chronic diseases such as diabetes and cancer, disease-related distress is known to impact disease management and health outcomes (Barry et al. J Health Psychol 2019). We sought to develop and validate an instrument to measure hemophilia-related distress (HRD). Methods: Using themes raised during qualitative interviews, questions were written to assess HRD. Questions were revised after review by clinicians and patient focus groups. The final formatted HRD instrument comprised 24 Likert scale questions (response level 0-5) plus a numerical rating of current distress on a 1-10 scale. The HRD total score is the sum of all domain scores and could range from 0-120 with lower scores indicating less HRD. Adults (≥18 years) with hemophilia receiving care at one of two hemophilia treatment centers were recruited to participate in the validation study. After informed consent, participants reported demographic and clinical information then completed the HRD instrument and questionnaires that measured characteristics similar to HRD including: the National Cancer Center Network (NCCN) Distress Thermometer, Kessler 6+ (K6), Patient Health Questionnaire (PHQ-9), Brief Pain Inventory (BPI), 5-level EuroQol-5D (EQ-5D-5L), Haem-A-Qol, Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment (WPAI), and PROMIS-29. Analysis included factor analysis and assessment of internal consistency using Cronbach's α, construct validity using Pearson's correlation coefficient and discriminant validity by comparing subgroups of patients. A subset of participants electronically completed the HRD instrument a second time within 7 days of initial assessment. Test-retest reliability was assessed using an interclass correlation coefficient (ICC). Results: Among 130 enrolled participants, 126 completed the HRD instrument in a median time of 5.4 minutes (Q1;Q3 3.5;14.4) with overall HRD scores ranged from 2-83 (median=31.5). Subject characteristics are shown in table 1. Factor analysis of 1-5 domains was undertaken with final selection of a 4-domain instrument (RMSEA 0.057 [90% CI 0.041,0.072]; CFI 0.97). The 4 domains are (# of items, Cronbach's α): Hemophilia Management Concerns (7 items, 0.81); Financial Concerns (3 items, 0.81); Perceived Self-efficacy (3 items, 0.79); Daily Function Concerns (7 items, 0.85). Assessment of convergent validity (table 2) demonstrated a moderate correlation (>0.60) of the HRD total score with the NCCN Distress Thermometer, Haem-A-Qol total Score, and PROMIS social role domain. The HRD 0-10 scale correlated well with NCCN Distress Thermometer, PHQ-9 score, EQ-5D Index score, Haem-A-Qol total score, PROMIS anxiety, depression, and pain interference domains. Domain 4 (Daily Function Concerns) was well correlated with Haem-A-Qol total score as well as physical health and view of self domains, WPAI total activity impairment, and PROMIS pain interference. The HRD total score and domains 1-4 were mild to moderately correlated with the K6 measure of general psychological distress (0.3-0.54, p< 0.05). Distress was higher among those with less education than standard college or graduate degree (median score 36 vs. 23, p=0.018), not employed (median total score 42 vs 26, p=0.002), and disabled (median score 43 vs 30, p=0.010). The total score was not significantly different among those with severe hemophilia compared with non-severe disease. However, domain 1 (hemophilia management concerns) was higher among those with non-severe disease (median 9 vs 6, p=0.033). Test-retest reliability was assessed in 38 subjects. ICC values were 0.84 (95% CI 0.71-0.91) for the total score and 0.56 (95% CI, 0.30-0.75), 0.51 (95% CI 0.40-0.81), 0.67 (95% CI 0.45-0.81) and 0.72 (95% CI 0.53-0.85) for domains 1-4 respectively. Conclusions: The HRD instrument measures the subjective emotional state associated with chronic management of hemophilia. The instrument demonstrates good internal consistency, construct and discriminant validity, and retest-reliability with a low responder burden. Interestingly HRD was not greater among those with severe disease, which in combination with results from analysis of domain 1, may reflect greater unease and less mastery in managing their disease among adults with non-severe hemophilia. Future studies can explore how HRD is associated with disease management and outcomes and healthcare utilization. Disclosures Kempton: Novo Nordisk: Research Funding; Octapharma: Honoraria; Genentech: Honoraria; Spark Therapeutics: Honoraria. Buckner:Genentech: Consultancy; Spark Therapeutics: Consultancy; Shire: Consultancy; Kedrion: Consultancy; Pfizer: Consultancy; Novo Nordisk: Consultancy.

Background: The Patient Reported Outcomes Measurement Information System (PROMIS) provides measures of health status that assess physical, mental, and social well-being from the patient perspective. As a complement to disease-specific measures, standardized PROMIS measures allow for comparisons across health attributes, health conditions, and with general populations. The validity and utility of PROMIS measures have been established in numerous adult and pediatric patient populations encompassing a broad range of diseases and chronic conditions but has not yet been evaluated in hemophilia. The aims of this study are to: 1) describe PROMIS measures reported by adults with hemophilia during routine non-acute care encounters, 2) assess how measures compare to those reported by the PROMIS reference sample, and 3) evaluate the sensitivity of PROMIS to indicators of hemophilia clinical severity. Methods: Adult hemophilia patients were recruited to participate in this cross-sectional study during routine clinic visits that occurred at either of two U.S. Hemophilia Treatment Centers during October 2017 through June 2018. After consent was obtained, participants completed the PROMIS-29 on a tablet. The PROMIS-29 short form includes 4 questions for each of 7 domains: depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities. Questions were based on the previous 7 days and used a 5-point response option. Responses were then scored on a T-score metric with a mean of 50 and a standard deviation (SD) of 10 based on the original PROMIS reference sample of US adults. Higher scores indicate worse severity for depression, anxiety, pain interference, fatigue, and sleep and better functioning for physical and social roles. Scores 5 or more away from 50 indicate at least mild impairment. Demographic characteristics were self-reported. Clinical characteristics including hemophilia severity (defined by factor levels) were obtained from medical records. Patients also completed the Brief Pain Inventory where they rated their average pain from 0-10. Responses were categorized as no (0), low (1-4), and high pain (5-10). Mean PROMIS measures were compared using T-tests or unadjusted linear regression. Results: Of 112 participants, 103 were males who completed the PROMIS questionnaire. Median age was 33 years and ranged from 18-75 years. Half had severe hemophilia and 60% reported using routine continuous factor prophylaxis. Two-thirds of patients reported no pain on average while another 14% reported high pain. Overall PROMIS scores for each domain among the hemophilia cohort were similar to scores reported in the PROMIS normative sample with mean T-scores near 50 (domain means ranged from 45.7-52.9). However, PROMIS domain scores differed significantly by certain characteristics revealing sub-groups of patients who experienced significantly worse health compared to the normative reference sample. Patients reporting higher average pain reported worse health across all 7 domains compared to those with less pain. Physical function was most impacted by pain: those reporting the highest pain reported worse physical function (mean=36.8, SD=7.9) compared to those with low (mean=41.6, SD=8.3) and no pain (mean=50.7, SE=7.7). Patients with HIV reported higher depression, anxiety, pain, and fatigue, and worse physical function compared to patients without HIV. An emergency department visit in the past 6 months was also related to worse depression, anxiety, fatigue, sleep, and social functioning. Scores did not vary by hemophilia severity, prophylaxis use, or current inhibitor status and were similar to those reported by the referent population. Conclusion: The 7 PROMIS domains were sensitive to several adult hemophilia disease severity indicators in a non-acute care setting. Overall scores reported by patients with hemophilia generally mirrored the normative PROMIS sample scores. However, patients with hemophilia who experienced pain reported scores significantly worse than the normative sample. PROMIS instruments provide a potentially valuable tool to study the impact of hemophilia and suggest usefulness in research and clinical practice. Additional studies are needed to assess responsiveness in PROMIS score with changes in disease status over time and in women with hemophilia. Disclosures No relevant conflicts of interest to declare.