Haemophilia Activities List Research Articles

Similar sports participation as the general population in Dutch persons with haemophilia; results from a nationwide study.

IntroductionAlthough sports participation is advocated in people with haemophilia (PWH), detailed data concerning sports participation in Dutch PWH is lacking.Aimto assess sports participation in Dutch PWH (6‐65 years) compared to the Dutch general population (GP).MethodsData from a nationwide, cross‐sectional study in PWH were analysed. Sports participation (type, duration, frequency) was assessed by the Modifiable Activities Questionnaire (MAQ), limitations in activities using the (Paediatric) Haemophilia Activities List ((Ped)HAL). Sports in the two highest categories according to the National Hemophilia Foundation classification were considered high‐risk sports. Groups were compared using Chi‐square testing.ResultsA total of 524 Adult PWH (median age: 45 (IQR: 30–55); 37% severe) and 126 paediatric PWH (median age: 11 (IQR: 8–14); 52% severe) were included. Sports participation was higher in adults (70%) than the GP (58%) and similar to the GP in children (PWH: 68%, GP: 72%). High‐risk sports participation decreased with age in PWH: from 65% (6‐12 years) to 17% (50‐65 years), which was also observed in the GP. Sports participation in children was independent of severity (non‐severe: 67% vs. severe: 65%; P = 0.97), but not in adults (non‐severe: 75%, severe: 62%; P < 0.01). Non‐severe PWH played more high‐risk sports than severe PWH: children at 65% vs. 48% (P = 0.05), adults at 25% vs. 15% (P = 0.07).DiscussionThese results suggest that sports participation in PWH was comparable to the GP. Sports participation was dependent of haemophilia severity in adults. Children were more involved in high‐risk sports than adults. More studies on sports‐related injury‐risk are needed for adequate counselling.

Aquatic exercise in patients with haemophilia: Electromyographic and functional results from a prospective cohort study.

Recurrent joint bleeds in haemophilia patients often cause musculoskeletal changes leading to functional capacity impairment. In this study, we assessed the effects of aquatic activities performed to improve functional capacity in these patients. The interventional protocol consisted of 24 hydrotherapy sessions during three months, in comparison with 24 swimming sessions. The pre- and post-intervention assessment consisted of Functional Independence Score, haemophilia joint health score (HJHS), Pediatric Haemophilia Activities List (PedHAL), surface electromyography (SEMG) of thigh muscles to assess muscle electric activity, and load cell on extensor and flexor thigh muscles to evaluate muscular strength. Forty-seven haemophilia patients were enrolled in this study, and 32 (23 severe haemophilia A, one moderate haemophilia A and 8 severe haemophilia B), median age 12y (6 to 40y), concluded the aquatic intervention. We observed a statistically significant increase with substantial improvement in functional capacity in the pre- and post-intervention evaluation of hydrotherapy in comparison with the swimming protocol, with HJHS (p=.006 and p=.001 respectively), PedHAL (Sum score) (p=.022 and p=.001) and score FISH (p=.021). The swimming group revealed significant improvements in muscular strength, in all muscles tested (p=.005 and p=.001). SEMG signal amplitude reached significantly higher levels in all muscles evaluated after both interventions except for the vastus medialis (right) in the hydrotherapy group. Our results concluded that both swimming and hydrotherapy were associated with physical improvement in haemophilia patients; however, only hydrotherapy lead to a more significant improvement in functional capacity.

Shortening the paediatric Haemophilia Activities List (pedHAL) based on pooled data from international studies.

IntroductionThe paediatric Haemophilia Activities List (pedHAL) was developed to measure activities and participation in children and youth with haemophilia. Results from international studies provide an opportunity to determine which items are universally important.AimThe aim of this study was to determine which items of the pedHAL are redundant to construct a shorter version of the pedHAL.MethodsThis study is a cross‐sectional multicentre secondary analysis on pooled data of published studies using the pedHAL (7 domains, 53 items, optimum score: 100) in children with haemophilia A/B aged 4–18 years. To identify redundant items, the following aspects were evaluated: floor and ceiling effects, proportions of missing and ‘not applicable’ responses, inter‐item correlations, component loadings in an exploratory factor analysis, internal consistency and item‐total correlations.ResultsData on 315 patients with haemophilia from 6 studies were evaluated. Median age was 12.2 years) (range 4.0–18.0), 87.3% had severe haemophilia and 80.3% received prophylaxis. Median (IQR) pedHAL sum score was 96.7 (88.0–100). After a stepwise procedure, 31 items were removed, resulting in a pedHALshort of 22 items, representing all original 7 domains. Most remaining items belonged to the domains ‘sitting/kneeling/standing’ and ‘functions of the legs’. The pedHALshort sum score was similar to the original pedHAL sum score, with small differences in 5 domains.ConclusionThis clinimetric study resulted in >50% reduction of the length of the pedHAL. The 22‐item pedHALshort reduces patient burden and is expected to capture the information on activities and participation. The pedHALshort needs validation in other populations.

The potential impact of gene therapy on health-related quality of life (HRQoL) domains in haemophilia

Abstract Introduction Haemophilia is an inherited bleeding disorder characterised by spontaneous bleeding, often leading to impaired health-related quality of life (HRQoL). Commonly used treatments include episodic and prophylactic treatment regimens. Gene therapies could soon become available, potentially creating a paradigm shift in patient management. Aim This paper proposes hypotheses about the potential impact of gene therapy on HRQoL domains in haemophilia, and how these impacts might differ compared with existing treatments. Methods An expert working group with 10 individuals experienced in haemophilia and HRQoL research was established to discuss potential impacts of gene therapy on HRQoL in general and for specific domains in haemophilia. As part of a one-day workshop, domains of three widely used patient-reported outcome (PRO) instruments were explored: the Haemo-QoL-A, the Patient Reported Outcomes, Burden and Experiences (PROBE), and the Haemophilia Activities List (HAL). Results The group expected a greater improvement in HRQoL from gene therapy compared with existing treatments for the following domains: physical/role functioning, worry, and consequences of bleeding (Haemo-QoL-A); haemophilia-related health and EQ-5D-5L (part of the PROBE); leg and arm function, and leisure activities (HAL). In contrast, the experts suggested that no change or potential deterioration might be observed for the emotional impact (HAL) and treatment concerns (Haemo-QoL-A) domains. Conclusions Current PRO instruments in haemophilia have limitations when applied in the context of gene therapy, and no single instrument fully captures the relevant HRQoL domains. However, the PROBE and Haemo-QoL-A were considered as the most suitable existing instruments. As haemophilia treatments evolve, further research should examine the potential effectiveness of existing PRO instruments as compared to the development of novel PRO measures.

Assessing the test-retest reliability and smallest detectable change of the Haemophilia Activities List.

IntroductionThe Haemophilia Activities List (HAL) is a preferred instrument to measure self‐reported limitations in activities in persons with haemophilia (PWH). Information on reliability and interpretability of HAL scores is lacking.AimTo examine the test‐retest reliability and smallest detectable change (SDC) of the HAL in adult PWH.MethodsFifty adult (≥18 years) persons with mild to severe haemophilia completed the HAL (42 items, 7 domains, optimum 100) at baseline (T0) and 3‐4 weeks later (T1). The intraclass correlation coefficient (ICC) and SDC were calculated for sum and component scores.ResultsFifty persons with haemophilia were included (median age 49 years; 92% haemophilia A; 70% severe haemophilia). The median (interquartile ranges) HAL sum score was 77 (62 to 99) at T0 and 81 (64 to 98) at T1. Reliability was good with ICCs for sum and component scores >0.9. The SDC for the sum score was 10.2, for the upper extremity component score 9.2, for the basic lower extremity component score 16.7 and for the complex lower extremity component score 13.4.ConclusionThe HAL has a good reliability for the sum and component scores. Score changes of the normalized sum HAL score greater than the SDC 10.2 indicate that the change was not a result of measurement error.

Physical activity levels in men with Haemophilia—A single centre UK survey

Historically persons with haemophilia (PWH) were not encouraged to participate in exercise due to the risk of bleeding and the lack of factor products available. This has now changed, and the availability of safe products allows PWH to be active and participate in sports. Studies have found that exercise has a positive effect on pain, joint health and movement with PWH. To record the amount and types of physical activity undertaken by a haemophilia population at a single treatment centre. An observational cross-sectional study to assess physical activity and quality of life of all registered patients over the age of 18 at the Oxford Haemophilia and Thrombosis Centre. Participants were posted questionnaires including the International Physical activity Questionnaire (IPAQ), Haemophilia Activity List (HAL), EQ-5D-5L and asked to list their physical activities. A total of 256 questionnaires were sent, with a 40% response rate for severe and 28% for mild patients. 85% met the UK physical activity guidelines. Sedentary behaviour for an average weekday was 6.4hours, and weekends were 5.3hours. Joint disease and severity type influenced the amount of activity undertaken, together with values for HAL and EQ-5D-5L. Twenty two types of activities were listed. It is encouraging to see the amount of physical activity PWH participate in, however, time spent in a sedentary state needs monitoring. PWH want to be active and the challenge for caregivers is to find activities they can do and strategies to maintain participation.

Movement behaviour patterns in adults with haemophilia.

Background:Joint bleeds are the hallmark of haemophilia, and can lead to disabling haemophilic arthropathy. Consequently, the movement behaviour of adults with haemophilia differs from that of healthy adults. It seems unlikely that a single outcome is able to reflect all relevant information regarding movement behaviour. The aim of the current study was to identify patterns of movement behaviour within persons with haemophilia (PWH) and compare clinical characteristics between patterns of movement behaviour.Methods:A total of 105 PWH [70% severe haemophilia; median age 43 years (30.0–54.0)] were included in the study. Hierarchical cluster analysis was used to identify patterns of movement behaviour. Clustering variables included seven parameters of movement behaviour: sitting, standing, walking, biking, running, frequency of active bouts and length of active bouts. Clinical characteristics included age, severity of haemophilia, joint health, physical functioning and pain. Clinical characteristics were compared between identified clusters by Kruskall–Wallis test. Movement behaviour was assessed with the Activ8 accelerometer, joint health was assessed on the Haemophilia Joint Health Score, physical functioning on the Haemophilia Activity List and the 40 m self-paced walk test and pain on the Numerical Pain Rating Score.Results:Cluster analysis identified three clusters, which were defined as: ‘sedentary’ (57%), ‘bikers and runners’ (22%) and ‘walkers’ (20%). The ‘bikers and runners’ showed better joint health and experienced fewer limitations in activities than the ‘walkers’ and the ‘sedentary’. The ‘walkers’ perceived fewer limitations in activities than the ‘sedentary’, with comparable joint health. We did not identify differences in pain, walking speed and age between the clusters.Conclusions:We identified three patterns of movement behaviour. The majority of PWH was identified as sedentary, whereas less sitting and regular walking during the day seemed to be more beneficial.

The Paediatric Haemophilia Activities List (pedHAL) in routine assessment: changes over time, child-parent agreement and informative domains.

IntroductionThe Paediatric Haemophilia Activities List (pedHAL) assesses self‐reported limitations in activities and participation in children with haemophilia.AimTo assess longitudinal changes, child‐parent agreement and to identify which pedHAL domains yielded most information in boys with access to early prophylaxis.MethodsThe pedHAL (53 items, 7 domains, optimum 100) was completed annually at the Van Creveldkliniek by boys aged 4‐18 years with moderate/severe haemophilia and their parents. Development of the pedHAL in relation to bleeds, changes per domain over 3‐5 years, child‐parent agreement (% difference child‐parent≤|5|) per domain and domain scores (limitations defined as ≤ 95) were determined.ResultsSeventy‐three patients and their parents (92% severe haemophilia, median age 13.1 years [range 5.4;18.0]) completed ≥1 pedHAL. Median (IQR) pedHAL sum score was 99.5 (95.2;100.0) for children and 99.6 (95.8;100.0) for parents. If patients scored >95 and had no joint and/or muscle bleed, 90.9% of the patients scored >95 at the next assessment. The median change in sum score was 0.0 for both the 3‐ and 5‐year interval. Child‐parent agreement varied between domains from 92% (‘self‐care’) to 71% (‘sitting/kneeling/standing’). Most limitations were reported in the domains ‘sitting/kneeling/standing’, ‘functions of the legs’ and ‘leisure activities and sports.’ConclusionIn routine clinical practice in Dutch children on prophylaxis, pedHAL scores were high and remained stable in 3‐5 years at group level. In individual patients without joint and/or muscle bleeds, pedHAL scores remained high after 1 year. Child‐parent agreement was not optimal which indicated that both child report and parent proxy should be reported.

PS1102 HEMOPHILIA ASSOCIATED BONE PATHOLOGY IMPACTS QUALITY OF LIFE

Background:People with Hemophilia (PwH) have decreased skeletal health resulting in lower bone mineral density (BMD) and greater risk of fracture. We previously identified the cytokines c‐terminal telopeptide (CTX)‐1, receptor activator of nuclear factor kappa‐B ligand (RANKL), and osteopretegerin (OPG) as critical markers for bone metabolism in hemophilia.Aims:This study investigates the relationship between hemophilia‐associated bone pathology, factors including cytokines, factor VIII (FVIII) replacement therapy, and quality of life.Methods:Twelve participants with severe FVIII‐deficiency were enrolled in the single site IRB‐approved study. After a 72‐hour washout, plasma samples were obtained at 8 time points over the course of five days with FVIII infusions administered on Day 1 (50 units/Kg) and Day 3 (20 units/Kg). All participants had a physical examination and completed questionnaires on Day 1. The EQ‐5D‐3L was used to report participants’ self‐rated health. The Hemophilia Activities List (HAL) self‐reported physical activity. The International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH‐BAT). BMD was measured as Z‐scores via Dual‐Energy X‐ray Absorptiometry (DEXA) Scanning. Joint assessment was performed using the Hemophilia Joint Health Score (HJHS). Plasma cytokine levels were measured using ELISA and magnetic bead multiplex kits.Results:Serum OPG concentrations increased throughout the study period (p = 7.26x10–5) while RANKL concentrations did not change (p = 0.19). The OPG:RANKL ratio exhibited a 6.2‐fold increase between Days 1 and 5. CTX‐1 concentrations were lower (p = 0.006) 30 minutes after the 50 U/kg FVIII infusion. CTX‐1 response for each participant was assessed using linear regression throughout the time course. Spine L1‐L4 Z‐score (SZ) and Hip Total Z‐score (HTZ) correlate with CTX‐1 response (p = 3.4x10–4 and 0.014, respectively). The mean age of participants was 25.2 ± 2.1 at time of first study visit. Participants had a mean SZ of −0.74 ± 0.34, HTZ of −0.17 ± 0.32, Hip Neck Z‐score (HNZ) of −0.16 ± 0.35, and HJHS of 20 ± 5. HTZ and HNZ decreased significantly with patient age (p = 0.027 and 0.032) while SZ and HJHS did not (p = 0.18 and 0.16). Consequently, age correction was applied to BMD comparisons. Statistical comparisons between HAL, EQ‐5D‐3L, and BHQ answers, BMD data, and HJHS are shown in Table 1.Summary/Conclusion:This prospective study demonstrates a relationship between FVIII deficiency and bone disease in PwH. OPG acts as a decoy ligand to RANKL, inhibiting osteoclastic bone resorption. The observed increase in OPG:RANKL ratio suggests FVIII has a direct impact on this pathway. Decreased CTX‐1 concentrations following factor infusion and correlations between CTX‐1 response and BMD further suggests that FVIII plays a role in moderating bone remodeling. Hemophilia‐associated bone and joint pathology is associated with decreased quality of life. Correlations between BMD and questionnaire responses demonstrate that poor bone and joint health is physically limiting, causes discomfort, and negatively impacts perceptions of personal well‐being. Furthermore, correlations between BMD and HJHS and ISTH‐BAT responses (Table 1) illustrate a relationship between bleeding management and skeletal health. PwH with lower BMD report more nose and gum bleeds, suggesting a link between FVIII replacement and skeletal health. Bleeds in the extremities were not correlated with decreased BMD or increased HJHS, but abdominal (stomach, iliopsoas) and other bleeds were. Analysis of these data is ongoing.image

Translation, validation and reliability of the functional capacity questionnaire Haemophilia Activities List for haemophilia patients in Brazil.

To date, none of the available assessment instruments to evaluate functional abilities for individuals with haemophilia has been translated and validated in Brazil. To translate, and test the construct validity, internal consistency and the reliability of the Haemophilia Activities List (HAL) for the Brazilian population with severe and moderate haemophilia (type A or B) and to investigate differences in the self-perception of functional abilities in patients adults with haemophilia classified according to the presence of joint bleeding and the performance of orthopaedic surgeries. The translation and transcultural adaptation following the steps: (a) translation; (b) synthesis (consensual version); (c) back-translation; (d) review by the committee of experts; (e) pretest in the target population; and (f) final version of the instrument. Correlations between HAL scores and the scores of the Health Assessment Questionnaire (HAQ) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were determined for construct validation. Reliability was tested using the test and retest method, and internal consistency was calculated by Cronbach's α. The HAL-BR was applied to 52 individuals with haemophilia (34.51±12.87years). The process of translation and cross-cultural adaptation produced similar versions between the translations A moderate correlation was observed between HAL and the HAQ (r=-0.55) and WOMAC scores (r=-0.58). The reliability was ICC=0.972, CI (0.917-0.997) ICC=0.876, CI (0.631-0.978) for inter- and intra-examiners. No difference was found in the total HAL score between the groups with and without bleeding. The group subjected to surgery compared to the group of not subjected to surgery presented in the HAL domains worse function in 'lying down/sitting/kneeling/standing', 'self-care' and 'complex lower extremities activities' as well as in total HAL score. The Brazilian version of the HAL was proven to be a valid and reliable evaluation tool for adults with haemophilia in Brazil.

Professional functioning of young adults with congenital coagulation disorders in the Netherlands.

Introduction and AimSuboptimal health‐related quality of life and lowered employment rates found in a previous study in young adults (YA) with congenital coagulation disorders (CCD) in the Netherlands underline the need for more insight into professional functioning of YA with CCD and into determinants of professional functioning.MethodsYoung adults (18‐30 years) with CCD participated in a cross‐sectional study. Professional functioning was assessed with the Work Productivity and Activity Impairment questionnaire (WPAI). Potential determinants were assessed with the Course of Life Questionnaire (CoLQ), Pediatric Quality of Life Inventory Young Adult version (PedsQL_YA), Illness Cognition Questionnaire (ICQ) and Haemophilia Activities List (HAL). Logistic regression analyses were performed in the complete sample of YA with CCD, and in YA men with haemophilia separately, to examine determinants of WPAI outcomes.ResultsNinety‐four YA (77 men; mean age 24.1 years, SD 3.5 and 17 women; mean age 24.5 years, SD 3.8) with CCD (74% haemophilia A/B) participated. 74.5% of YA were paid employed for on average 30 hours per week. Of these, more than a quarter reported work impairment. Older age and a non‐severe type of haemophilia (in the sample of YA men with haemophilia) were associated with successful (paid) employment. No variables were associated with professional functioning (expressed as Presenteeism and Overall work impairment) in patients with CCD or haemophilia.ConclusionThree‐quarters of YA with CCD were successful in finding paid employment. Though absenteeism was low, YA with paid employment needs attention as a considerable part experienced work impairment.

Opportunities for Improvement: The Lot of the Inhibitor Patient Is Not a Happy One

INTRODUCTIONHemophilia A or B carries significant morbidity - progressive throughout life. The mainstay of treatment is regular factor replacement to treat or prevent bleeding episodes. Up to 30% of Hemophilia A and up to 5% of Hemophilia B develop neutralizing antibodies (inhibitors) rendering factor replacement therapy ineffective. Hemophilia patients with inhibitors are managed with bypassing agents for treatment or prevention of bleeds.Prophylaxis is not adequate in inhibitor patients using currently available bypassing products due to their very short half-life (2-3 hours for rFVIIa; 5-6 hours for aPCC) so they are treated on an episodic basis for bleeds. On-demand treatment results in poor quality of life, significantly higher mortality and inferior musculoskeletal outcomes in inhibitor patients when compared to patients without inhibitors. The quality of life of hemophilia has been evaluated using EQ-5D and Haem-A-QOL and impaired activity has been measured with Haemophilia Activity List (HAL). The EQ-5D is a widely used internationally validated general-purpose quality of life instrument however it lacks granularity and is not specific to Hemophilia. Haem A-QOL (Mackensen et al 2004) and Hemophilia Activities List (HAL) (Van Genderen FR et al 2006.) were developed and validated specifically to address the typical disabilities and life issues faced by patients with Hemophilia.Marzeptacog alfa (activated) (MarzAA) was created using a structure-based rational protein design and has 4 amino acid substitutions to enhance the biological properties of FVIIa. This variant molecule has substantially (6-7x) greater potency than wild-type FVIIa, a greater half-life and sufficient bioavailability when given subcutaneously (SQ).There is currently a paucity of data on quality of life (QoL) of inhibitor patients. We evaluated the baseline QoL and functional activity of inhibitor patients enrolled in the MAA-201 study using the EQ-5D , Haem-A-QoL and HAL compared the results to those of reference hemophilia patients without inhibitors.METHODS A phase 2 / 3 open-label study evaluating safety and efficacy of MarzAA in hemophilia patients with inhibitors is underway MAA-201, (NCT03407651)Subject eligibility required an annualized bleeding rate of >12 and documented inhibitor to replacement factor. The primary aim of the trial was the complete prevention of breakthrough bleeding for 50 days by the daily administration of a fixed SQ dose of MarzAA. If breakthrough bleeding occurred, up to three dose escalations were permitted. At baseline and study conclusion, each subject completed quality of life assessment tools the EQ-5D, Haem-A-QOL and the Hemophilia Activities ListHaem-A-QOL assesses subjects across ten domains and provides a summarized score. Subjects in the present trial (MARZAAPOP) were compared to baseline values for subjects with severe hemophilia but without inhibitors recruited into a long-term prophylaxis trial (The A-LONG trial - ALONGREFPOP).Mean baseline Haem-A-QOL summed score in the A-LONG trial was 29.3 ±15.7 contrasting sharply with a mean baseline summed score of 42 ±15.2 for subjects in the present trial (Table 1)HAL is more motor function oriented and assesses patients across ten domains of which seven assess basic functionality and three are composites intended to assess disability in performing complex tasks. HAL provides both raw and normalized scores. Normalized scores provide meaningful output in the case of missing data elements. For each domain and for the sum score, a raw score of 0 and a normalized score of 100 indicates no functional deficit. Figure 1 provides a visual comparison between recruited subjects (MARZAAPOP) in the present trial and the population used to validate the HAL tool. (HALREFPOP).CONCLUSION: In examining recruits into the present trial, it is clear that inhibitor patients have generally worse functional scores than either of two reference groups. Effective long-term prophylaxis is expected to produce measurable improvement in QOL scores in this hard-to-treat population. DisclosuresBooth:Catalyst Biosciences: Consultancy. Mahlangu:Sanofi: Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; LFB: Consultancy; NovoNordisk: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Chugai: Consultancy; Catalyst Biosciences: Consultancy, Research Funding; Biomarin: Research Funding, Speakers Bureau; Biogen: Research Funding, Speakers Bureau; Bayer: Research Funding; Amgen: Consultancy; Alnylam: Consultancy, Research Funding, Speakers Bureau; Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau; Spark: Consultancy, Research Funding. Levy:Catalyst Biosciences: Employment, Equity Ownership.

Reliability and validity of patient-reported outcome instruments in US adults with hemophilia B and caregivers in the B-HERO-S study.

To assess the reliability and validity of six patient-reported outcomes (PRO) instruments for evaluating health-related quality of life in adults with mild-severe hemophilia B and caregivers of children with hemophilia B, including affected women/girls. Adults with hemophilia B and caregivers completed separate online surveys containing several PRO instruments, which were administered to adult participants only (EQ-5D-5L, Brief Pain Inventory v2 Short Form, Hemophilia Activities List, and International Physical Activities Questionnaire), both adults and caregivers (Patient Health Questionnaire [PHQ-9]), or caregivers only (Generalized Anxiety Disorder 7-Item [GAD-7] scale). Construct validity and item-total correlation were assessed using Pearson product-moment correlation, internal consistency was assessed using Cronbach's alpha coefficient, and known-group validity was assessed by comparisons to self-reported characteristics based on the Kruskal-Wallis test. Patient-reported outcomes instruments generally showed satisfactory reliability for adults (n=299) and caregivers (n=150). In adults, PRO instruments generally showed high construct validity. Most PRO instruments showed expected significant differences among known groups for adults and caregivers. PHQ-9 and GAD-7 did not show significant differences among caregiver age groups. Patient-reported outcomes instruments administered in B-HERO-S demonstrated reliability and validity in the broader population of adults with hemophilia B and caregivers when including all severities and genders.

Investigating the relationship between the HJHS and HAL in routine clinical practice: A retrospective review.

Comprehensive musculoskeletal assessment for monitoring joint health in haemophilia includes both physical assessment with Haemophilia Joint Health Score (HJHS) and assessment of self-reported function by Haemophilia Activities List (HAL). Correlation between physical assessment and joint function was undertaken between HJHS and HAL in patients with SHA and SHB who had both assessments at the same visit over a one-year period. Data from 120 patients (96-SHA/24=SHB) with a median age 33years (range 19-73) were included. Median total HJHS was 19, increasing with age: 18-30years-7, 31-50years-25 and 51-73years-44. Similarly, median total HAL score was 80 with decreased function associated with increasing age: 18-30years-90.4, 31-59years-71.7, 51-73years-49.5. Median Total HJHS and HAL demonstrated strong correlation (rs =0.66, P<0.01). Moderate-to-strong correlations were seen across the entire age group between the HJHS LL and UL subtotals and corresponding limb HAL domains. Within age groups, correlations were less significant particularly for the upper UL domains in HAL and the UL HJHS score. The wide range of ROM in joints categorized as markedly affected (ie, ROM loss score=3) highlights the potential ceiling effect of this domain score and its use in chronically damaged joints. HJHS and HAL showed moderate-to-strong correlation with discrepancy in some individual patients. Prospective studies are required to better understand the clinical utility of both especially in severe joint disease where HAL may have a potential advantage.

The reliability and validity of the Chinese version of the adult haemophilia activities list

Objective To test the the reliability and validity of the Chinese version of the adult haemophilia activities list (HAL). Methods A Chinese version of the HAL was prepared by translation, back-translation and revision. Adult hemophilia patients were used to test it and a short-form arthritis impact measurement scale (AIMS-SF) simultaneously. A total of 98 valid questionnaires were collected. The internal consistency, reliability, split-half reliability, content validity, construct validity and convergent validity were tested. Results The Cronbach′s α coefficients for the total questionnaire and its dimensions were all 0.7 or more. The half-reliability test produced a Spearman correlation coefficient of 0.97. The Pearson correlation coefficients relating each dimension score with the total score and each dimension′s entry score with the dimension score were all greater than 0.6. The correlation coefficient between the dimensions of the two questionnaires was smaller than the correlation coefficients relating each dimension with the total scale. There was relatively good correlation between the HAL sum score and the AIMS2-SF sum score (r=0.640, P≤0.01), as well as between the HAL sum score and the AIMS2-SF physical score (r=0.576, P≤0.01). Conclusion The Chinese version of the adult HAL has good reliability and validity. Key words: Haemophilia; Arthritis; Activity; Assessment; Reliability; Validity

The Jamaican Haemophilia Registry: Describing the burden of disease.

Jamaica has an estimated 200 persons with haemophilia (PWH), who face significant constraints in access to specialized haemophilia care, including access to clotting factor concentrates. The aim of this paper is to establish the current burden of disease in PWH in Jamaica. PWH were enrolled through the University Hospital of the West Indies, Jamaica. The impact of haemophilia was assessed using a comprehensive battery of heath outcome measures that included the following: laboratory, clinical information and validated outcome measures of joint structure and function, activity, and health-related quality of life (HRQoL) to provide a health profile of the Jamaican haemophilia population. In all, 45 PWH were registered (mean age: 29, range: 0.17-69years), including 13 children (<18years of age) and 32 adults. In this sample, 41 had haemophilia A (30 severe) and 4 had haemophilia B (3 severe); 10 patients with haemophilia A were inhibitor positive. The results indicate that adults with haemophilia in Jamaica have significant joint damage: mean Haemophilia Joint Health Score (HJHS)=42.1 (SD=17.3); moderate activity levels - mean Haemophilia Activities List (HAL) score=64.8 (SD=17.8); and low HRQoL scores - mean Haemo-QoL-A score=62.3 (SD=19.4). Results for children are also reported but should be interpreted with caution due to the small sample size. There is a very high burden of disease in PWH in Jamaica. The health profiles reported in this paper are an essential first step in advocating for a multidisciplinary Comprehensive Care Program for assessment and care of PWH in Jamaica.

Patient-reported outcomes and joint status across subgroups of US adults with hemophilia with varying characteristics: Results from the Pain, Functional Impairment, and Quality of Life (P-FiQ) study.

Pain and functional impairment associated with joint disease are major problems for people with hemophilia, and impact on health-related quality of life (HRQoL) may vary across groups defined by demographic and treatment-related characteristics. To evaluate differences in overall HRQoL, pain, function, and joint status between P-FiQ study subgroups. Adult males with hemophilia and a history of joint pain/bleeding completed a pain history and the patient-reported outcome instruments EQ-5D-5L, Brief Pain Inventory v2 Short Form (BPI), International Physical Activity Questionnaire (IPAQ), and Hemophilia Activities List (HAL); optionally, joint status was assessed (Hemophilia Joint Health Score v2.1 [HJHS]). Scores were analyzed between subgroups across sets of participant characteristics. A total of 381 adult males with hemophilia were enrolled, with median age of 34years. Worse scores on EQ-5D-5L index, BPI pain severity/interference, HAL overall score, and HJHS were generally associated with being college educated, unemployment, self-reporting both acute and chronic pain, and self-reporting anxiety/depression. Measures of joint status and HRQoL were consistently lower in participants who had higher educational levels, were unemployed, self-reported having both acute and chronic pain, and self-reported having anxiety/depression. A greater understanding of the association of these factors with disease outcomes may improve individualized patient management.

Assessments of pain, functional impairment, anxiety, and depression in US adults with hemophilia across patient-reported outcome instruments in the Pain, Functional Impairment, and Quality of Life (P-FiQ) study.

Pain, functional impairment, anxiety, and depression associated with joint disease may affect health-related quality of life (HRQoL) in people with hemophilia. To report detailed patient-reported outcomes (PRO) assessments related to HRQoL in participants in the Pain, Functional Impairment, and Quality of Life (P-FiQ) study. Pain and HRQoL were assessed via PRO instruments in US adult males with hemophilia A or B and a history of joint pain or bleeding. PRO instruments included EQ-5D-5L with visual analog scale, Brief Pain Inventory v2 Short Form, SF-36v2, and Hemophilia Activities List. Instrument domain and item responses were described. Responses were collected from 381 adult males with a median age of 34years. Pain was observed across instruments and affected daily activities and quality of life. Respondents reported functional impairment that limited the kind of work and activities they participated in, with activities involving the lower extremities being most affected. A high prevalence of mental health disorders was identified across instruments. Pain and HRQoL were evaluated using multiple PRO instruments, which vary in timescales of assessment and levels of detail. More consistent clinical assessments and patient dialog regarding pain and aspects of HRQoL may help drive improved outcomes.

Factors associated with pain severity, pain interference, and perception of functional abilities independent of joint status in US adults with hemophilia: Multivariable analysis of the Pain, Functional Impairment, and Quality of Life (P-FiQ) study.

Levels of pain and dysfunction appear to differ among people with hemophilia despite similar levels of joint disease. To determine patient characteristics that influence pain and function independent of joint status. US adults with hemophilia completed a survey that included information on clinical characteristics, demographics, and patient-reported outcome instruments assessing pain (Brief Pain Inventory v2 Short Form [BPI]), functional impairment (Hemophilia Activities List [HAL]), and health status (EQ-5D-5L). Additionally, physiotherapists optionally completed a clinical joint evaluation (Hemophilia Joint Health Score [HJHS]). Associations were examined using simple and multiple regression models. Of 381 adults enrolled, 240 had complete HJHS scores (median age, 32years). After controlling for HJHS and opiate use, anxiety/anxiolytic use was significantly associated with worse pain severity and interference scores. After controlling for HJHS, the most significant predictors of functional impairment were older age, unemployment, more severe hemophilia, and greater pain. EQ-5D-5L pain/discomfort was associated with worse outcomes on most HAL scores. Unemployment, anxiety, and depression were each associated with both greater pain and functional disability after controlling for joint status. Continued attention to pain and psychosocial issues will be important in improving clinical care and research efforts in the hemophilia population.

Self-reported activity of Swedish persons with haemophilia: Change over 2.5 years.

To describe self-reported activity using the Haemophilia Activity List (HAL) for Swedish adults with haemophilia and to detect any changes over time. The HAL was sent to the adult population with haemophilia A and B, moderate and severe form, living in Sweden (n = 260). Participants completed the HAL and a questionnaire on sociodemographic and medical information. From a previous study cohort, 61 persons had responded twice to the HAL. The investigated group was divided into early and later treatment onset groups with regard to access to medication. The response rate was 50%. There was a significant difference (p < 0.001) between the early and later treatment groups in all domains in HAL. When analysing HAL "question by question" from the 2 reported time-points, the most prominent outcome was that the reported ability in activities was stable over time at the group level, except for participants who had no access to the clotting factor early in life. They reported greater limitations in some of the activities in the challenging domain "leisure activities and sport". The early treatment group reported a significantly better ability in all activities compared with the late treatment group.