Test-retest reliability of a mobile application of the patient reported outcomes burdens and experiences (PROBE) study.

INTRODUCTION: The Patient Reported Outcomes, Burdens, and Experiences (PROBE) questionnaire is a patient-reported outcome tool that assesses quality of life and disease burden in people with haemophilia (PWH). AIM: To assesses the test-retest reliability of PROBE when completed using the mobile phone application. METHODS: We recruited PWH, including carriers, and individuals with no bleeding disorders who attended haemophilia-related workshops or via social media. Participants completed PROBE three times (twice on the app: T1 and T2, and once on the web, T3). Test-retest reliability was analysed for T1 versus T2 (app to app, time period one) and T2 versus T3 (app to web, time period two). RESULTS: We enrolled 48 participants (median age = 56 [range 27-78] years). Eighteen participants (37.5%) were PWH and seven (14.6%) were carriers. On general health domain questions, we found almost perfect agreement, except for a question on the frequency of use of pain medication in the last 12 months [Kappa coefficient (κ) .72 and .37 for time period one and two, respectively] and any use of pain medications (κ .75) for time period two. For haemophilia-related questions, we found substantial to perfect agreement, except for the questions on the number of joint bleeds in the previous 6 months for time period one (κ .49) and the number of bleeds in the previous two weeks for time period two (κ .34). CONCLUSIONS: The results demonstrate the reliability of the PROBE app. The app can be used interchangeably with the paper and web platforms for PROBE administration.

A pilot study of US HTC physical therapists' concordance of PT MASAC recommendations and educational needs.

INTRODUCTION: Physical therapists (PTs) are essential providers within the Hemophilia Treatment Centers (HTCs) team caring for persons with inherited blood disorders (PWBD). OBJECTIVE: Little is known regarding PTs understanding and concordance of MASAC PT Recommendations (MASAC#238), educational resources used to maintain competency and support for a mentorship programme. METHODS: PTs at federally funded HTCs were eligible to participate in a descriptive non-validated study exploring: (i) demographics, (ii) educational background, (iii) experience in evaluation and treatment of PWBD, (iv) practice patterns indicative of concordance with MASAC#238 and (v) opinion regarding PT mentorship. RESULTS: Respondents experience caring for PWBD ranged 1-36 years, treating both adults and children. Although most acknowledged awareness of MASAC#238, dropout (14/44, 31.8%) was noted; 28/30 (93.3%) who continued were aware of the recommendations. Level of concordance with MASAC#238 varied (range 64.3%-96.2%) regarding: signs/symptoms, treatment of muscle/joint bleeding and pre/post synovectomy and knee replacement treatment. Many PTs identified patients as individual and unique, thus not all recommendations may apply. PTs utilised available educational programmes. No relationships were noted regarding years of practice, education and years caring for PWBD. All respondents favoured a mentorship programme citing benefits, but also outlined barriers. CONCLUSIONS: Provision of necessary financial support for optimal function of a full-time PT within the HTC can enhance standards of care for PWBD. Supporting educational opportunities may enhance concordance with current MASAC PT Recommendations. Respondents valued development of a structured, hands-on mentorship programme. MASAC#23 has recently been updated in May 2023 to MASAC#275.

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: facilitating research through infrastructure, workforce, resources and funding.

BACKGROUND: The National Hemophilia Foundation (NHF) conducted extensive, inclusive community consultations to guide prioritization of research in coming decades in alignment with its mission to find cures and address and prevent complications enabling people and families with blood disorders to thrive. RESEARCH DESIGN AND METHODS: With the American Thrombosis and Hemostasis Network, NHF recruited multidisciplinary expert working groups (WG) to distill the community-identified priorities into concrete research questions and score their feasibility, impact, and risk. WG6 was charged with identifying the infrastructure, workforce development, and funding and resources to facilitate the prioritized research. Community input on conclusions was gathered at the NHF State of the Science Research Summit. RESULTS: WG6 detailed a minimal research capacity infrastructure threshold, and opportunities to enable its attainment, for bleeding disorders centers to participate in prospective, multicenter national registries. They identified challenges and opportunities to recruit, retain, and train the diverse multidisciplinary care and research workforce required into the future. Innovative collaborative approaches to trial design, resource networking, and funding to surmount obstacles facing research in rare disorders were elucidated. CONCLUSIONS: The innovations in infrastructure, workforce development, and resources and funding proposed herein may contribute to facilitating a National Research Blueprint for Inherited Bleeding Disorders.

Research is critical to advancing the diagnosis and care of people with inherited bleeding disorders (PWIBD). This research requires significant infrastructure, including people and resources. Hemophilia treatment centers (HTC) need many different skilled care professionals including doctors, nurses, and other providers; also statisticians, data managers, and other experts to process patients' clinical information into research. Attracting diverse qualified professionals to the clinical and research work requires long-term planning, recruiting individuals in training programs and retaining them as they become experts. Research infrastructure includes physical servers running database software, networks that link them, and the environment in which these components function. US Centers for Disease Control and Prevention (CDC) and American Thrombosis and Hemostasis Network (ATHN) coordinate and fund data collection at HTCs on the health and well-being of thousands of PWIBD into a registry used in research studies.National Hemophilia Foundation (NHF) and ATHN asked our group of health care professionals, technology experts, and lived experience experts (LEE) to identify the infrastructure, workforce, and resources needed to do the research most important to PWIBD. We identified the types of CDC/ATHN studies all HTCs should be able to perform, and the physical and human infrastructure this requires. We prioritized finding the best clinical trial designs to study inherited bleeding disorders, identifying ways to share personnel and tools between HTCs, and innovating how research is governed and funded. Involving LEEs in designing, managing, and carrying out research will be key in conducting research to improve the lives of PWIBD.

Integrated Hemophilia Patient Care via a National Network of Care Centers in the United States: A Model for Rare Coagulation Disorders.

Rare, chronic diseases such as hemophilia and other congenital coagulation disorders require coordinated delivery of services for optimal outcomes. Hemophilia Treatment Centers (HTCs) are specialized, multidisciplinary health-care centers providing team-based care to meet the physical, psychosocial, and emotional needs of people with hemophilia (PWH) and may serve as a model for other rare coagulation disorders. Health-care purchasers, as well as the general medical community, may not appreciate the breadth and quality of services provided by HTCs. They exemplify the acculturalization and actualization of integrated care by providing comprehensive diagnostic and treatment services that reduce morbidity, mortality, avoidable emergency room visits, hospitalizations, and overall costs, while promoting a longer lifespan and improved patient functioning and outcomes. This is accomplished by a team-based approach relying upon a shared decision-making model to effectively prevent complications and manage symptoms in PWH, who are dependent on high-cost treatments. This article provides a concise yet comprehensive description of the core components of an HTC and the regional and national networks in the United States, which together achieve their incomparable value for all stakeholders.

Evaluation of the sexual health in people living with hemophilia.

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.

Non-severe haemophilia: Is it benign? - Insights from the PROBE study.

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.

Exploring regional variations in the cross-cultural, international implementation of the Patient Reported Outcomes Burdens and Experience (PROBE) study.

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.

Test-retest properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire and its constituent domains.

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.

Psychometric properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire.

OBJECTIVE: To assess the psychometric properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire. METHODS: This 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. RESULTS: The 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. CONCLUSIONS: The 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 NUMBER: NCT02439710; Results.

Impact of hemophilia B on quality of life in affected men, women, and caregivers-Assessment of patient-reported outcomes in the B-HERO-S study.

INTRODUCTION: Health-related quality of life (HRQoL) is impaired in patients with hemophilia; however, the impact in mild/moderate hemophilia B and affected women is not well characterized. OBJECTIVE: To evaluate factors that affect HRQoL in adults with hemophilia B and caregivers of affected children. METHODS: US adult patients and caregivers of affected children completed distinct ~1-hour online surveys including patient-reported outcome instruments. RESULTS: In total, 299 adult patients and 150 caregivers participated. Adults with moderate hemophilia reported poorer health status (median EQ-5D-5L index score, 0.63) than those with mild (0.73) or severe (0.74) hemophilia. Women reported greater pain severity than men on the Brief Pain Inventory v2 Short Form (median, 7.00 vs 5.00). Based on the Patient Health Questionnaire, mild or worse depression was observed in >50% of adult respondents, and depression was reported more often in those with moderate and severe hemophilia vs those with mild hemophilia. Most caregivers reported at least mild depression. CONCLUSION: Pain, functional impairment, and depression/anxiety are present at higher-than-expected levels in individuals with hemophilia B. The large proportion of individuals with mild/moderate hemophilia and women with reduced health status suggests significant unmet needs in this population.

Impact of mild to severe hemophilia on engagement in recreational activities by US men, women, and children with hemophilia B: The Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study.

The psychosocial impact of hemophilia on activities was recently investigated in the Hemophilia Experiences, Results and Opportunities (HERO) study (675 people with hemophilia and 561 caregivers of children with hemophilia in 10 countries). The impact of hemophilia B may not be accurately reflected in the HERO results, as ~75% of respondents described issues affecting males with hemophilia A. To address the needs of this population, the Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B-HERO-S) was developed as a pilot study in the United States in collaboration with the hemophilia community. The analysis reported here assessed engagement in recreational activities and changes to treatment regimens around activities as reported by 299 adults with hemophilia B and 150 caregivers of children with hemophilia B. Nearly all adults with hemophilia B (98%) experienced a negative impact on their participation in recreational activities due to hemophilia-related issues, and most caregivers (90%) reported that hemophilia B had a negative impact on their child's engagement in recreational activities. One of the main reasons identified for discontinuing past activities was the risk of bruising or bleeding (adults/children with hemophilia B, 49%/41%). In particular, adults with hemophilia B reported a history of activity-related bleeding, and most adults decreased their participation in high-risk activities as they aged. Substantial percentages of adults and children with hemophilia B (including mild/moderate severity) altered their treatment regimens to accommodate planned activities. These findings may help inform guidelines for individualizing treatment regimens around participation in recreational activities based on hemophilia severity, baseline factor level, and activity risk and intensity.

Impact of mild to severe hemophilia on education and work by US men, women, and caregivers of children with hemophilia B: The Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study.

The psychosocial impact of hemophilia on work was recently investigated in the Hemophilia Experiences, Results and Opportunities (HERO) study. The findings revealed that hemophilia had an impact for adults with moderate/severe hemophilia and caregivers of children with hemophilia. HERO did not specifically evaluate impact on education in adults/children with mild/moderate hemophilia or the impact on employment of spouses/partners of caregivers of affected children. The Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study evaluated the impact of hemophilia on the lives of adult men/women with mild-severe hemophilia B and caregivers of boys/girls with hemophilia B and their spouses/partners. Many adults with hemophilia B (94%) reported that hemophilia had a negative effect on their ability to complete a formal education, often attributed to the inability to attend or concentrate in school as a result of hemophilia-related bleeding or pain. Most adults with hemophilia B (95%) and caregivers/partners (89%/84%) indicated that hemophilia had a negative impact on employment. Most adults with hemophilia were employed (81%), with construction/manufacturing (35%) as the most frequently reported industry; many worked in jobs requiring manual labor (39%). Of those unemployed, 62% never worked, and those who stopped working reported that they left the workforce due to financial issues (59%), including insurance coverage/co-pays, or hemophilia-related issues (55%). Nearly one-third of caregivers voluntarily left the workforce to care for children with hemophilia. These results suggest a need to focus more effort on career counseling for adults with hemophilia B and caregivers of affected children, especially around mild/moderate hemophilia, as this population may not be as well informed regarding potential impact in school and the workplace.

Management of US men, women, and children with hemophilia and methods and demographics of the Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study.

The Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B-HERO-S) initiative was launched in an effort to address specific gaps in the understanding of the psychosocial impact of mild-moderate-severe hemophilia B. The original Hemophilia Experiences, Results and Opportunities (HERO) qualitative study evaluated the needs of people with hemophilia A or B in multiple countries; however, a majority of participants had the more common moderate-severe hemophilia A. The B-HERO-S study was designed in collaboration with the hemophilia community to evaluate the needs of adults with hemophilia B and caregivers of children with hemophilia B, including affected women and caregivers of girls with hemophilia. The report presented here describes participant demographics and comorbidities, as well as treatment regimens and access to treatment. Bleeding symptoms were reported by 27% of mothers of children with hemophilia B who participated. Women were more likely than men to self-report arthritis and depression/anxiety as comorbidities associated with hemophilia B. More adults and children with hemophilia B were on routine treatment than on on-demand treatment, and a high percentage of adults with moderate hemophilia B received routine treatment (86%). Many adults with hemophilia B (78%) and caregivers (69%) expressed concern about access to factor in the next 5 years, and of adults with hemophilia B, women more commonly experienced issues with access to factor in the past than did men (72% vs 44%). The findings of the B-HERO-S study reveal potential unmet needs of some patients with mild-moderate hemophilia B, and the results may be leveraged to inform patient outreach by hemophilia treatment centers and education initiatives.

Treatment outcomes, quality of life, and impact of hemophilia on young adults (aged 18-30 years) with hemophilia.

The Hemophilia Experiences, Results and Opportunities (HERO) initiative assessed psychosocial issues reported by people with moderate to severe hemophilia and was led by a multidisciplinary international advisory board. This analysis reports data from young adult respondents (aged 18-30 years), including both US and overall global (including US respondents) results, and investigates treatment outcomes, quality of life, and impacts of hemophilia on relationships. More young adults in HERO received prophylaxis than on-demand treatment, although a majority reported not using factor products exactly as prescribed, and 50% of global respondents and 26% of US respondents reported issues with access to factor replacement therapy in the previous 5 years. Many young adults with hemophilia reported comorbidities, including bone/skeletal arthritis, chronic pain, and viral infections, and nearly half of young adults reported anxiety/depression. Most reported pain interference with daily activities in the past 4 weeks, although a majority reported participating in lower-risk activities and approximately half in intermediate-risk activities. Most young adults were very or quite satisfied with the support of partners/spouses, family, and friends, although roughly one-third reported that hemophilia affected their ability to develop close relationships with a partner. A majority of young adults reported that hemophilia has had a negative impact on employment, and 62% of global respondents and 78% of US respondents were employed at least part-time. Together these data highlight the psychosocial issues experienced by young adults with hemophilia and suggest that increased focus on these issues may improve comprehensive care during the transition to adulthood.