Haemophilia Activities List Research Articles

Clinical Outcomes of Total Knee Arthroplasty in Patients Who Have Hemophilic Arthropathy: A Prospective Study

BackgroundTotal knee arthroplasty (TKA) is considered the gold standard treatment for patients who have advanced hemophilic knee arthropathy. However, special considerations are required for these patients. This prospective study reports on the need for soft-tissue procedures, implant types, complication rates, mean 53.3 months implant survivorship, and patient-reported outcome measures of TKA in hemophilic patients. MethodsThere were twenty primary TKAs that were performed on 15 hemophilic patients from 2012 to 2023. The mean follow-up was 53.3 months (range, 6 to 128). The necessity for additional soft tissue procedures, implant type, complications, and revision rates were recorded. Knee Injury and Osteoarthritis Outcome Score, Knee Society Score, Hemophilia-specific Quality of Life Questionnaire for Adults, Hemophilia Activities List, and range of motion, were compared preoperatively and at the last follow-up. ResultsAt the last follow-up, implant survivorship was 90%. There were 2 revisions: one for aseptic loosening and one for periprosthetic joint infection. Additional soft tissue procedures included 2 quadriceps snips (10%). Tibial augments, tibial stubby stems, and both tibial and femoral traditional stems were used in one (5%), 4 (20%), and one (5%) TKAs, respectively. A constrained posterior-stabilized bearing was necessary in one case. Clinically and statistically significant improvements were found between the preoperative and final follow-up values of all patient-reported outcome measures, knee flexion (73 versus 108 °, P < 0.001), and flexion contracture (11 versus 4 °, P = 0.002). ConclusionsThis study showed that TKA, in patients who have hemophilic knee arthropathy, is a reliable treatment option that improves knee function and patients’ quality of life with acceptable implant survival rates at midterm follow-up (mean 53.3 months). Standard implants and approaches can be used in most cases. Despite good outcomes, hemophilic patients carry additional risks for complications that require specific considerations. It is paramount for these patients to be treated in specialized centers by experienced surgeons to achieve good results.

Humanistic burden of haemophilia A without inhibitors: A cross-sectional analysis of the HemoLIFE study.

To evaluate the impact of haemophilia A without inhibitors on humanistic outcomes in patients and caregivers. Herein, we report a cross-sectional analysis of the baseline data of persons with haemophilia (PWH) participating in the prospective study HEMOLIFE. These data are part of a prospective, observational, and multicentre study currently being conducted in 20 hospitals in Spain by haematologists. We included subjects 12 years or older diagnosed with haemophilia. The evaluations included the Maladjustment Scale, Haemophilia-Specific Quality of Life Questionnaire for Adults (HaemoQol)/HaemoQol Short Form (Children), haemophilia-specific version of the Work Productivity and Impairment Questionnaire plus the Classroom Impairment Questionnaire (WPAI+CIQ:HS), Haemophilia Activity List (HAL)/Paediatric Haemophilia Activities List (pedHAL), visual analogue scale (VAS) for evaluating pain, Coping Pain Questionnaire-Reduced (CAD-R), and Hospital Anxiety and Depression Scale (HADS). A total of 81 PWH were recruited at 18 centres; 66 PWH were ≥18 years (i.e., adults), and PWH 15 were <18years (i.e., paediatric patients). Out of the 79 evaluable subjects, 16 (20%) showed an impact of haemophilia on daily life, and the areas most affected were "leisure time" (58% showed maladjustment) and "work/studies" (47% showed maladjustment). Patients reported a higher impact of haemophilia on quality of life (mean [SD] of the transformed score) in the dimensions of "sport" (49.4 [28.6]), "physical health" (40.5 [25.8]) and "future" (37.7 [28.9]). In adults, according to HAL scores, greater impairment of function was observed in "lying/sitting/kneeling/standing," "function of legs" and "leisure activities and sports," with mean normalized scores of 64.7, 65.1 and 69.0, respectively. Productivity was mostly impacted by presenteeism. The pain was infrequent and moderate. According to the HADS scores, nine (11.5%) patients had clinical anxiety and depression. PWH without inhibitors exhibited impairments in adjustment, quality of life and functionality, especially related to leisure and sports activities, and exhibit relevant levels of anxiety and depression.

Association Between Leg Muscle Thickness and Walking Test With the Hemophilia-Specific Functional Parameters.

The aim of the study is to evaluate the muscle thickness and walking test in people with hemophilia A and their correlation to joint health and functional impairments. This is a cross-sectional study. Twenty-nine severe/moderate people with hemophilia A were enrolled. Muscle thickness of quadriceps and medial gastrocnemius was measured using ultrasound. Joint health and functional capacity were assessed using Hemophilia Joint Health Score, Hemophilia Early Arthropathy Detection with Ultrasound, 6-Minute Walking test, Hemophilia Quality of Life Questionnaire for Adults, and Hemophilia Activities List. Quadriceps muscle thickness significantly correlated with Hemophilia Joint Health Score knee, Hemophilia Early Arthropathy Detection with Ultrasound knee, and Hemophilia Activities List. Calf muscle thickness significantly correlated with the Hemophilia Joint Health Score ankle. After adjusted age and body mass index, calf muscle thickness was inversely associated with the Hemophilia Joint Health Score ankle. Six-Minute Walking test was found to significantly correlate with Hemophilia Joint Health Score total, Hemophilia Early Arthropathy Detection with Ultrasound total, Hemophilia Quality of Life Questionnaire for Adults, and Hemophilia Activities List. Muscle thickness and the distance of 6-Minute Walking Test were linked to assessment of joint health, quality of life, and activity participation in people with hemophilia A. Ultrasound measurement of muscle thickness and walking test seem to be useful tools for the assessment of joint health and functional status in people with hemophilia A.

Reliability and construct validity of the ACTIVLIM-Hemo and Haemophilia Activities List (HAL) questionnaires in individuals with haemophilia.

The objective of this study is to assess the reliability and construct validity of ACTIVLIM-Hemo, a newly developed Rasch-built questionnaire designed to evaluate activity limitations in people with haemophilia (PwH), in comparison with the Haemophilia Activities List (HAL), which was developed using Classical Test Theory. A total of 130 participants with haemophilia A or B were included. They underwent various assessments, including joint health scoring (HJHS), functional tests (TUG and 2MWT) and completed questionnaires such as the BPI, IPAQ, HAL and ACTIVLIM-Hemo. Reliability indices and the minimum detectable change (MDC95) were determined for ACTIVLIM-Hemo and for HAL. Construct validity was evaluated through correlations and multiple linear regression, considering demographic and clinical factors. Both ACTIVLIM-Hemo (Person Separation Index=0.92) and HAL (Cronbach's α=0.98) demonstrated high reliability. The MDC95 for ACTIVLIM-Hemo represented 11.6% of its measurement range, while for HAL, it amounted to 18/100 score points. Activity limitations measured by both instruments were significantly correlated with demographic and clinical factors. Joint health (HJHS), pain severity (BPI) and walking performance (2MWT) emerged as the main predictors of activity limitations, explaining 75% of the variance in ACTIVLIM-Hemo and 60% in HAL. ACTIVLIM-Hemo stands as a reliable and valid instrument for assessing activity limitations in PwH. Both instruments exhibited significant correlations with demographic and clinical factors, but ACTIVLIM-Hemo displayed a more homogeneous construct. Given its linear scale and lower MDC95 and better targeting, ACTIVLIM-Hemo shows promise as a patient-centric instrument for assessing responsiveness to treatment during individual follow-up.

The Correlation of Muscle Mass and Walking Distance with Joint Health and Functional Status in Hemophilic Arthropathy Among People with Hemophilia a (PwHA)

Introduction: Hemophilic arthropathy resulting from repeat joint bleeding is a common complication for people with hemophilia (PWH), despite the current prophylaxis therapy. Monitoring the status of musculoskeletal health for PWH is necessary. Muscle plays a critical role in maintaining and promoting the joint health. Muscle atrophy is one of the key features of haemophilic arthropathy. Up to date, there are more studies focusing on joint health of PWH but few having attention on the impact of limbs muscles on joint status of PWH. Clinical assessments such as muscle circumference and manual muscle strength tests fail to detect subtle muscle changes. The study aimed to evaluate the ultrasound measurement of muscle thickness in people with hemophilia A (PwHA) and its correlation to joint health and functional impairments. Methods and Materials: In the observational cross-sectional study, 29 PwHA (median age 35 years; range 13-63) were enrolled, including 27 severe-type diseases on prophylaxis therapy and 2 moderate-type diseases on episodic treatment. Muscle thickness of quadriceps and medial gastrocnemius were measured by ultrasound. Joint health and functional capacity were assessed using Haemophilia Joint Health Score (HJHS), Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US), Haemophilia Quality of Life Questionnaire for Adults (Haemo-A-QoL), and Haemophilia Activities List (HAL). 6-Minute Walking Test (6MWT) for global functional evaluation. Results: At the time when the 29 patients receiving this survey of joint health, there were 28 on rFVIIIFc treatment for an average of 31.2 months (mean: 33.5, range 19.5－43), among whom 26 severe-type patients had rFVIIIFc prophylaxis and 2 moderate-type patients had on-demand therapy with rFVIIIFc. Only one severe-type patient had received non-rFVIIFc product prophylaxis for &amp;gt; 3 years. Totally 174 joints were examined. By correlation analysis, a significant correlation was found between both quadriceps and calf muscle thickness and the HJHS knee and ankle scores, respectively, with a negative correlation ( r= -0.45, p=0.015*, right quadriceps; r= -0.60, p&amp;lt;0.001***, left quadriceps; r= -0.39, p=0.039*, right calf; r= -0.58, p&amp;lt;0.001***, left calf). A significant correlation between muscle thickness and HEAD-US was observed between quadriceps muscle and knee score, with a negative correlation ( r= -0.56, p=0.017*, right quadriceps; r= -0.36, p=0.0048**, left quadriceps). Therefore, Quadriceps muscle thickness significantly correlated with HJHS knee, HEAD-US knee, and HAL. Calf muscle thickness significantly correlated with the HJHS ankle. After adjusted age and BMI, calf muscle thickness was significantly associated with the HJHS ankle. Muscle thickness was also observed to correlate with Haem-A-QoL and HAL. 6MWT was found to significantly correlated with HJHS total, HEAD-US total, Haem-A-QoL, and HAL ( r= -0.42, p=0.0231*, HJHS; r= -0.52, p=0.0037**, HEAD-US; r= -0.60, p&amp;lt;0.0001***, Haem-A-QoL; r= 0.64, p&amp;lt;0.001***, HAL). Conclusion: For the first time, limbs muscle thickness and the distance of 6MWT were linked to assessment of joint health, quality of life and activity participation in PwHA. Ultrasound measurement of muscle thickness appears to be a reliable tool for the assessment of muscle mass in PwHA.The 6MWT also appears to be useful tool for assessment of physical capacity and endurance in PwHA. Disclosures: No relevant conflicts of interest to declare.

Health-related quality of life following valoctocogene roxaparvovec gene therapy for severe hemophilia A in the phase 3 trial GENEr8-1

BackgroundSevere hemophilia A (HA) negatively impacts health-related quality of life (HRQOL). ObjectivesWe aimed to analyze HRQOL in adult men with severe HA without inhibitors after valoctocogene roxaparvovec gene transfer in the phase 3 trial GENEr8-1. MethodsParticipant-reported outcomes were the hemophilia-specific quality of life questionnaire for adults (Haemo-QOL-A), the EQ-5D-5L instrument, the Hemophilia Activities List (HAL), and the Work Productivity and Activity Impairment Questionnaire: Hemophilia Specific (WPAI+CIQ:HS). Participants completed the questionnaires at baseline and through 104 weeks postinfusion with 6 × 1013 vg/kg of valoctocogene roxaparvovec. Scores were analyzed per participant characteristics and outcomes. ResultsFor 132 HIV-negative participants, mean change from baseline in Haemo-QOL-A Total Score met the anchor-based clinically important difference (CID: 5.5) by week 12; the mean (SD) increase was 7.0 (12.6) at week 104. At week 104, improvement in Consequences of Bleeding, Treatment Concern, Worry, and Role Functioning domain scores exceeded the CID (6). EQ-5D-5L Utility Index scores improved above the CID at week 52, but not at week 104. EQ-5D-5L visual analog scale and HAL scores increased from baseline to week 104. Participants reported less activity and work impairment at week 104 than baseline. Participants with problem joints had lower mean baseline Haemo-QOL-A Total and domain scores than those without them, but improved over 104 weeks, except for 11 participants with ≥3 problem joints. Participants with 0 bleeds during the baseline prophylaxis period reported Haemo-QOL-A score improvements above the CID, including in the Consequences of Bleeding domain. ConclusionValoctocogene roxaparvovec provided clinically meaningful HRQOL improvement for men with severe HA.

Physical Activity Limitations In Children With Severe Haemophilia A. Does Emicizumab Make A Difference?

To assess the effect of emicizumab on physical activity in children with severe haemophilia A. The prospective cohortstudy was conducted from October 2021 to April 2022 at the Paediatric Department of Kafrelsheikh University Hospital, Egypt, in collaboration with the Haematology out-patient clinic of the Paediatric Department, Zagazig University, Egypt, and the Paediatric Department of Cairo University Hospital, Egypt, and comprised children aged 4-18 years with severe haemophilia A who received emicizumab prophylaxis. Paediatric Haemophilia Activities List was used to assess physical activity at baseline and aftersix months of regular emicizumab prophylaxis. Data was analysed using SPSS 26. There were 29 children, all (100%) boys, with mean age 8.7±3.51 years(range 4-15 years. Of them, 17(58.62%) patients were negative for inhibitors. Median Paediatric Haemophilia Activities Listsum score was 59.54 (interquartile range: 50.15-62.05) at baseline which moved up to 84 (interquartile range: 79.05-86.35) post-intervention (p<0.001). Emicizumab prophylaxis improved the level of physical activity in children with severe haemophilia A.

Functional decline in persons with haemophilia and factors associated with deterioration

The World Haemophilia Federation advises regular musculoskeletal assessment covering all International Classification of Functioning and Health (ICF) domains, including limitations in activities and participation in persons with haemophilia (PWH). This enables clinicians to detect changes early and enable adjustments in personalized healthcare when needed. However, data on the course of physical functioning and occurrence of decline is lacking. The aim of this study is to describe changes in perceived limitations in activities of PWH and to identify factors associated with a change. Data were collected from medical health records of regular check-up visits of adults with moderate and severe haemophilia in two time periods. Perceived limitations in activities was measured with the Haemophilia Activities List (HAL). Association between variables (e.g., age, body mass index, bleeding rate and synovitis) and change in perceived limitations was assessed using a generalized linear model. A total of 104 PWH were included. At T0, the median HAL sum score was 79.5 (IQR 62.1-93.6) and at T1 the median HAL sum score was 74.2 (IQR 57.5-88.3). A functional decline was found in 35.6% of PWH, 55.8% remained stable and 8.7% improved. Among other variables, a BMI>30kg/m2 appeared to be an important factor that negatively influenced the change in perceived functioning in adult PWH. With the included factors we could only explain a small part of this decline (R2 adj : .12). The majority of PWH remained stable in their perceived functional ability over mid-long term (median 3.5 years). However, about a third showed a clinical relevant decline in their functional ability.

ACTIVLIM-Hemo: A new self-reported, unidimensional and linear measure of activity limitations in persons with haemophilia.

To assess activity limitations in people with haemophilia (PwH), the self-reported Haemophilia Activity List (HAL) is widely employed, despite several methodological limitations impacting the interpretation of categorical scores. Modern psychometric approaches avoid these limitations by using a probabilistic model, such as the Rasch model. The ACTIVLIM is a Rasch-built measurement of activity limitations previously validated in several clinical conditions like neuromuscular disorders. This study sought to develop the ACTIVLIM-Hemo, meaning an ACTIVLIM scale version specifically adapted to assess daily activity limitations in adult PwH. Daily activities were assessed as "impossible," "difficult" or "easy" by 114 PwH (median age of 44 years) with 63 of them reassessed after 12 days. The Rasch Rating Scale model was used to identify activities delineating a unidimensional and linear scale unbiased by demographic and clinical status. Concurrent validity was determined through correlation with the HAL sub-scores and sum score. The ACTIVLIM-Hemo included 22 pertinent activities, with difficulties independent of demographic and clinical conditions, allowing a reliable measure of activity limitations (PSI=.92) expressed on a linear and unidimensional scale in PwH (7%-100 % range, ceiling effect of 1/114) with excellent test-retest reliability (ICC=.978). Spearman rank correlations between ACTIVLIM-Hemo and HAL sub-scores ranged between .623 and .869. The ACTIVLIM-Hemo is an easy-to-administer, valid and reliable alternative to HAL in assessing activity limitations in PwH. Its invariant scale can be used across conditions and time to compare the functional status of PwH over a wide measurement range.

Activity and participation in haemophiliacs: Item response modelling based on international classification of functioning, disability and health.

There is scant research investigating the user-friendly functional assessment tool conceptualized by the International Classification of Functioning, Disability and Health (ICF) among persons with haemophilia (PWH). This study aims to accomplish two goals: (1) quantifying comprehensive functioning measures of haemophilia through Item Response Theory (IRT); (2) discussing patient-centred care based on the Wright map of personal ability and item difficulty. A cross-sectional study was carried out in 70 PWH (mean age, 33.09±11.04) via convenience sampling. All patients completed the 45 ICF categories of haemophilic-specific activity and participation. Psychometric properties of the categories were examined using Mokken scale analysis and parametric item response modelling. We extracted a unidimensional scale with 31 categories, and constructed a Rasch model with good fitness. The Cronbach's α of the scale was .9713, with the Guttman's λ2 =.9730, Molenaar Sijtsma ρ=.9802, and latent class reliability coefficient=.9769, indicating great internal reliability. The estimated individual social competence by the Rasch model was highly related to the index score of the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) (p<.001, r=.62), and had a moderate correlation (p<.001, r=.54) with the score of Haemophilia Activities List (HAL). The ICF scale of haemophilicactivity and participation with 31 categories (HAPPY-ICF) has good construct validity and internal consistency. The person-item threshold distribution map might be helpful in research and clinical practices for patient-oriented care.

Proof of concept and feasibility of a blended physiotherapy intervention for persons with haemophilic arthropathy.

Regular physiotherapy with a physiotherapist experienced in the field is not feasible for many patients with haemophilia. We, therefore, developed a blended physiotherapy intervention for persons with haemophilic arthropathy (HA) (e-Exercise HA), integrating face-to-face physiotherapy with a smartphone application. The aim of the study was to determine proof of concept of e- Exercise HA and to evaluate feasibility. Proof of concept was evaluated by a single-case multiple baseline design. Physical activity (PA) was measured with an accelerometer during a baseline, intervention and post-intervention phase and analysed using visual inspection and a single case randomisation test. Changes in limitations in activities (Haemophilia Activities List [HAL]) and a General Perceived Effect (GPE) were evaluated between baseline (T0), post-intervention (T1) and 3 months post-intervention (T2) using Wilcoxson signed rank test. Feasibility was evaluated by the number of adverse events, attended sessions and open-ended questions. Nine patients with HA (90% severe, median age 57.5 (quartiles 50.5-63.3) and median HJHS 32 (quartiles 22-36)) were included. PA increased in two patients. HAL increased mean 15 (SD 9) points (p=.001) at T1, and decrease to mean +8 points (SD 7) (p=.012) at T2 compared to T0. At T1 and T2 8/9 participants scored a GPE>3. Median 5 (range 4-7) face-to-face sessions were attended and a median 8 out of 12 information modules were viewed. No intervention-related bleeds were reported. A blended physiotherapy intervention is feasible for persons with HA and the first indication of the effectiveness of the intervention in decreasing limitations in activities was observed.

Efficacy of Efanesoctocog Alfa on Physical Functioning: Results from the XTEND-1 Phase 3 Clinical Trial in Previously Treated Patients with Hemophilia A

Background: Adults with severe hemophilia A may have reduced levels of physical functioning significantly impacting their health-related quality of life (HRQoL). Results from the Phase 3 XTEND-1 study demonstrated that once-weekly efanesoctocog alfa prophylaxis was well-tolerated and provided superior bleed protection compared with prior factor VIII (FVIII) prophylaxis. Objective: To evaluate the efficacy of once-weekly efanesoctocog alfa prophylaxis on physical functioning in adults and adolescents (≥12 years of age) with severe hemophilia A who were previously treated with standard of care FVIII prophylaxis. Methods: XTEND-1 (NCT04161495) was a phase 3, open-label, multicenter trial in previously treated patients (≥12 years of age) with severe hemophilia A. Patients received once-weekly prophylactic efanesoctocog alfa, 50 IU/kg for 52 weeks (Arm A) or on-demand efanesoctocog alfa, 50 IU/kg for 26 weeks followed by 26 weeks of once-weekly prophylaxis ([50 IU/kg]; Arm B). Physical functioning was assessed as a secondary endpoint using hemophilia-specific HRQoL questionnaire for adults (Haem-A-QoL; in patients ≥17 years of age), Patient-Reported Outcomes Measurement Information System (PROMIS)-Short Form v2.0 physical function (PF; in patients ≥18 years of age), and as exploratory endpoints using Hemophilia Activities List (HAL; in patients ≥18 years of age), and EuroQol- 5 Dimension-5 Level (EQ-5D-5L; mobility and usual activities domains). Exit interviews, ActiGraph Activity Monitors (worn for 8 consecutive days at intervals throughout the study period), and post-hoc analysis (including psychometric analyses) were also used to evaluate physical functioning. The mean change from baseline to Week 52 in Haem-A-QoL Physical Health (PH) score, PROMIS PF 6b T-score, and HAL overall score, along with 95% confidence interval (CI) were estimated by a mixed-effect model with repeated measures. Here we report results for patients in Arm A. Results of the exit interviews and Actigraphy were evaluated in the overall patients included in the trial (Arms A and B). Results: A total of 159 patients (Arm A, N=133; Arm B, N=26) were included in the XTEND-1 trial. At baseline, the Haem-A-QoL PH score (mean [standard deviation, SD]) was 37.02 (23.83), while the overall HAL score was 76.11 [20.73]. A total of 18% (22/122) and 9% (11/122) patients reported moderate to severe problems with mobility and usual activities, respectively, at baseline, as per EQ-5D-5L. Prophylactic treatment with efanesoctocog alfa resulted in significant improvement in physical health: least square (LS) mean change in the Haem-A-QoL PH score from baseline to Week 52 was -6.74 (95% CI: -10.13 to -3.36; P=0.0001). Psychometric analyses reported meaningful within-group change for Haem-A-QoL PH score of 6.8 (range: 4.8-6.8) defined in the context used in the study. Numerical improvement was observed in PROMIS PF 6b T-score (LS mean change from baseline: 0.56 [95% CI: -0.38 to 1.50] and in HAL overall score at Week 52 (LS mean change: 0.67 [95% CI: -2.03 to 3.38]). A total of 23.5% (27/115) patients reported an improvement in at least 1 category in mobility at Week 52, while usual activities improved in 19.1% (22/115) patients in the EQ-5D-5L scale. These improvements in physical functioning on various instruments were aligned with the results from the exit interviews (N=29, including 17 patients in Arm A) reporting improvement in physical functioning in most patients (26/29). In addition, trends of improved physical activity were also observed in the Actigraphy data (mean [SD]: 5376 [3796] steps/day at baseline versus 5758 [4472] steps/day at Week 52; overall patients, N=158, including 132 patients in Arm A). Conclusions: Once-weekly prophylaxis with efanesoctocog alfa resulted in improvement in physical functioning in patients with hemophilia A, positively impacting daily living activities, in patients who were on prior standard of care FVIII prophylaxis.

Validation of the patients-specific functional scale in patients with haemophilia.

A complete functional assessment is essential to measure health status and treatment effects in patients with haemophilia. The Patient-Specific Functional Scale (PSFS) is a reliable, valid, simple and quick scale that measures physical function in patients with musculoskeletal disorders. However, the reliability and validity of the PSFS have not been evaluated in patients with haemophilia. The aim of this study was to validate the Patient-Specific Functional Scale in patients with haemophilia. Twenty-eight patients with haemophilia participated in the study. They completed the PSFS and the Haemophilia Activity List (HAL) scales by telephone during an initial session, and then repeated the assessment in a follow-up session 1week apart. Reliability was analysed by the internal correlation coefficient (ICC), the standard error of measurement (SEM) and the smallest detectable change (SDC). The concurrent validity of the PSFS was determined by correlating the initial score of the PSFS scale to the initial score of the HAL scale. Correlations were calculated by means of scatter plots and Pearson product-moment r correlation coefficient. ICC and SEM values showed excellent reliability for the PSFS scale, with a SDC of 1. A significant moderate correlation was found between the results of the PSFS and the HAL (r=.57, P <.001). The PSFS is a reliable and valid scale to measure the functionality of people with haemophilia.

Ankle joint distraction is a promising alternative treatment for patients with severe haemophilic ankle arthropathy.

Haemophilic ankle arthropathy (HAA) causes major morbidity. When conservative treatment fails, major surgical interventions are indicated. An alternative treatment to maintain joint mobility and postpone these interventions is desired. To gather prospective data on clinical/structural changes after ankle joint distraction (AJD) in HAA. This study includes patients with severe HAA insufficiently responding to conservative treatment. AJD was performed during 8-10weeks by use of an external frame. Questionnaires, physical examination and radiology were used to evaluate pain, function and structural changes before and 6, 12, 24 and 36months after distraction. Mixed effect models were used for analysis. This study includes eight cases (21-53years). The fixed effects estimates of the visual analogue score (0-10) improved from 7.5 at baseline to 3.4 (p=.023) 3years after distraction. The Haemophilia Activities List (HAL, 0-100) for basic/complex lower extremities functions improved from respectively 29.6 and 31.5 to 54.3 (p=.015) and 50.7 (p=.031). Joint mobility was maintained. Magnetic resonance imaging (MRI) showed thickened cartilage and reduced bone marrow oedema and subchondral cysts. Pin tract infections (n=6) were effectively treated and no adverse bleeding events occurred. At 3-year follow-up, in none of the patients the originally indicated arthrodesis was performed. This first prospective study showed that AJD in HAA results in decreased pain, improved function and decreased arthropathy-related MRI findings in the majority of patients for prolonged time. Although the study population is small and follow-up is relatively short, AJD may be promising to postpone invalidating interventions and might be a breakthrough treatment.

Validation of the pedHALshort and HALshort in Dutch children and adults with haemophilia.

The Haemophilia Activities List (HAL) and paediatric HAL assess self-reported limitations in various daily activities. To reduce patient burden, shorter versions of the pedHAL (22 items) and HAL (18 items) have been developed. This study aimed to determine the agreement between the pedHAL/HALfull and pedHAL/HALshort and construct validity and internal consistency of the pedHAL/ HALshort in persons with haemophilia (PWH). A cross-sectional secondary analysis of the Hemophilia in the Netherlands-6 national survey was performed. Adult and paediatric PWH completed the original pedHAL/HALfull , from which pedHAL/ HALshort were derived. Score differences between the original and short versions were calculated. Construct validity was studied by testing hypotheses regarding the relationship of the pedHAL/HALshort with the pedHAL/HALfull , Haemophilia & Exercise Project Test-Questionnaire (HEP-Test-Q), Canadian Haemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT) and RAND 36-item Health Survey (RAND-36) (convergent/discriminant validity) as well as its ability to discriminate between subgroups (known-group validity). Internal consistency was assessed with Cronbach's α. We included 113 children (median 10y [range 4-17], 53% severe haemophilia) and 691 adults (median 51y [range 18-88], 35% severe). Scores of the pedHAL/HALfull and pedHAL/HALshort were similar with high correlations (>0.9). Construct validity was confirmed for the pedHAL/HALshort . The HALshort was able to discriminate between different disease severities and ages. Cronbach's α of the pedHAL/HALshort was 0.95-0.97. This study confirmed the agreement between the pedHAL/HALfull and the pedHAL/HALshort and the construct validity of the pedHAL/HALshort . The next step is to study construct validity of the pedHAL/HALshort when administered as short forms.

The Hemophilia Joint Health Score version 2.1 Validation in Adult Patients Study: A multicenter international study

BackgroundThe Hemophilia Joint Health Score (HJHS) was developed and validated to detect arthropathy in children. Additional evidence is required to show validity in adults. We studied the convergent and discriminant construct validity of the HJHS version 2.1(HJHSv2.1) in adults with hemophilia. A secondary aim was to define age‐related normative adult HJHSv2.1 reference values. MethodsWe studied 192 adults with hemophilia, and 120 healthy adults in four age‐matched groups—18 to 29, 30 to 40, 41 to 50, and >50 years—at nine centers. Trained physiotherapists scored the HJHS and World Federation of Hemophilia (WFH) joint score. Health history, the Functional Independence Scale of Hemophilia (FISH), Hemophilia Activities List (HAL), and Short‐Form McGill Pain Questionnaire (SF‐MPQ) were also collected. ResultsThe median age was 35.0 years. Of participants with hemophilia, 68% had severe, 14% moderate, and 18% mild disease. The HJHS correlated strongly with WFH score (Spearman’s rho [rs] = .95, P < .001). Moderate correlations were seen between the FISH (rs = .50, P < .001) and SF‐MPQ Present Pain Intensity (rs = .50, P < .001), while a modest correlation was found with the HAL (rs = −.37, P < .001). The HJHS significantly differentiated between age groups (Kruskal‐Wallis T = 35.02, P < .001) and disease severity in participants with hemophilia. The HJHS had high internal reliability (Cronbach’s α = .88). We identified duration of swelling as a redundant item in the HJHS. ConclusionsThe HJHS shows evidence of strong convergent and discriminant construct validity to detect arthropathy in adults with hemophilia and is well suited for use in this population.

Validity of the four‐square step test in persons with haemophilia

Recurrent bleeds into joints causes arthropathy leading to pain and reduced joint movement. This may cause a reduction in postural balance and increase the falls risk in patients with haemophilia (PWH). With an ageing PWH population the need to assess functional balance in clinic will be essential to monitor function and implement interventions to help maintain balance and prevent falls. To assess the utility of the Four-Square Step Test (FSST) in PWH. 80 PWH of all severity types were recruited and underwent a battery of outcome measures: FSST, Timed up & go (TUG), Short performance physical battery (SPPB), Haemophilia Activity List (HAL), ABC confidence questionnaire, and Haemophilia Joint Health score (HJHS). Demographics were collected, together with self-reported falls/trips history. All 80 participants were able to complete all test measures. Median age 44.5years. Number of participants reporting falls ranged from 23% in severe to 3% in mild. Recent trips 53% severe to 17% mild. Excellent Inter and intra-reliability, ICC of .981 (CI .953-.992), P<.001 and ICC .989 (.983-.993) P<.001, respectively. Strong correlations between FSST and TUG/ SPPB .753 and -.728, moderate correlation between FSST and ABC/HAL -.484, -.464 P<.01. FSST is a valid and safe measure to use in PWH. It correlates strongly with other functional measures, has excellent inter and intra rater reliability. FSST correlates with age rather than severity type and provides information to the clinician on the speed/ability to change direction and clear an obstacle. ABC questionnaire was able to differentiate between severities and offers insight into patient confidence to move. SPPB had a ceiling effect with 52/80 scoring 12 and may not be suitable for PWH.

Validation of PROMIS Profile‐29 in adults with hemophilia in the Netherlands

BackgroundThe Patient‐Reported Outcomes Measurement Information System (PROMIS) Profile‐29 questionnaire is widely used worldwide, but it has not yet been validated in the Netherlands, nor in persons with hemophilia. ObjectiveTo validate the Dutch‐Flemish version of the PROMIS‐29 Profile v2.01 in adults with hemophilia. MethodsDutch males with hemophilia (all severities) completed questionnaires that contained sociodemographic and clinical characteristics, the PROMIS‐29, RAND‐36, and the Hemophilia Activities List (HAL). Structural validity of each subscale was assessed with confirmatory factor analysis (CFA). Internal consistency was calculated for each subscale with sufficient model fit in CFA. Construct validity was assessed by testing hypotheses about (1) correlations of each PROMIS‐29 subscale with corresponding scales of RAND‐36 and domains of HAL, and (2) mean differences in T‐scores between subgroups with different hemophilia severities, self‐reported joint impairment, and HIV infection status. We considered ≥75% of data in accordance with the hypotheses evidence for construct validity. ResultsIn total, 770 persons with hemophilia participated in this cross‐sectional study. CFA revealed sufficient structural validity for five subscales: Physical Function, Depression, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. Internal consistency was high and Cronbach's alpha ranged from 0.79 for Sleep Disturbance to 0.96 for Pain Interference. Differences between clinical subgroups were in the expected direction. Construct validity was confirmed for Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, and Pain Intensity. ConclusionThis study revealed sufficient evidence for structural validity, internal consistency, and construct validity for most PROMIS Profile‐29 subscales among people with hemophilia in the Netherlands.

Shortening the Haemophilia Activities List (HAL) from 42 items to 18 items.

IntroductionThe Haemophilia Activities List (HAL) was developed to measure activities and participation in persons with haemophilia (PWH). Shortening the questionnaire may facilitate use of the HAL.AimThe aim of this study was to determine which items of the HAL are redundant, to construct a shorter version of the HAL, and to determine the construct validity of the HALshort.MethodsA secondary analysis was performed on pooled data of two published studies using the HAL (seven domains, 42 items, optimum score: 100) in adults with haemophilia A/B. Data were divided into a derivation (62%) and a validation set (38%). Redundant items were identified by evaluation of: 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. Correlations with the SF‐36 and EQ‐5D‐5L were used to determine construct validity of the HALshort.ResultsData on 680 PWH were evaluated. In the derivation dataset (n = 420), median age was 30 years (range 18–80), 43% had severe haemophilia and 61% received prophylaxis. Median (IQR) HAL sum score was 65.0 (55.7–88.8). The stepwise procedure resulted in a HALshort of 18 items with a median sum score of 63.3 (54.4–86.7). Construct validity was similar for the HAL and HALshort in the validation dataset (n = 260).ConclusionThis clinimetric study resulted in a >50% shortening of the HAL. The 18‐item HALshort reduces patient burden and is expected to capture the information on activities and participation. The HALshort needs further validation.

Correlations between Patient-Reported Outcomes and Self-Reported Characteristics in Adults with Hemophilia B and Caregivers of Children with Hemophilia B: Analysis of the Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) Study

Correlations between Patient-Reported Outcomes and Self-Reported Characteristics in Adults with Hemophilia B and Caregivers of Children with Hemophilia B: Analysis of the Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) Study