Impact of joint status on contraction steadiness of m. quadriceps femoris in people with severe haemophilia

Impaired contraction steadiness of lower limb muscles affects functional performance and may increase injury risk. We hypothesize that haemophilic arthropathy of the knee and the strength status of quadriceps are relevant factors which compromise a steady contraction. This study addresses the questions if impaired steadiness of the quadriceps is verifiable in people with haemophilia (PWH) and whether a connection between the status of the knee joint and quadriceps strength exists. A total of 157 PWH and 85 controls (C) performed a strength test with a knee extensor device to evaluate their bilateral and unilateral maximal quadriceps strength and steadiness. Isometric steadiness was measured by the coefficient of variation of maximum peak torque (CV‐MVIC in %). For classification of the knee joint status the World Federation of Haemophilia (WFH) score was used. Lower steadiness (higher CV values) was found in PWH compared with C during bilateral [PWH vs. C; 0.63 (0.36/1.13) vs. 0.35 (0.15/0.72), median (Q25/Q75) P < 0.001] and unilateral trials [left leg: 0.70 (0.32/1.64) vs. 0.50 (0.23/1.04), P < 0.05; right leg: 0.68 (0.29/1.51) vs. 0.39 (0.18/0.68), P < 0.001]. PWH with a WFH score difference (≥1) between their extremities showed a less steady contraction in the more affected extremity (P < 0.05). More unsteady contractions have also been found in extremities with lower quadriceps strength compared with the contralateral stronger extremities (P < 0.001), whereby the weaker extremities were associated with a worse joint status (P < 0.001). The results of this study verify an impaired ability to realize a steady contraction of quadriceps in PWH and the influence of joint damage and strength on its manifestation.     

Proprioception,dynamic balance and maximal quadriceps strength in females with knee osteoarthritis and normal control subjects

Background: Osteoarthritis (OA) is one of the most common musculoskeletal complaints worldwide. The knee is the most frequently involved joint of the lower limb in OA. Knee joint proprioception, dynamic balance and maximal quadriceps strength may be impaired in patients with knee OA. Objective: To investigate whether females with knee OA have reduced knee joint proprioception, balance responses and quadriceps strength compared with normal controls. Methods: We undertook a cross‐sectional study of 30 females with knee OA and 30 controls. Knee joint proprioception was measured using electrogoniometer. Dynamic balance response was determined using a step test. Quadriceps strength was measured isometrically using a modified Tornvall chair. Results: Subjects with OA had greater mean error, poorer dynamic balance and less quadriceps strength than non‐symptomatic ones (P < 0.001). Increasing age was associated with a decline in proprioceptive acuity for both controls and patients (r = 0.40, P < 0.001). In subjects with knee OA, decreased dynamic balance was associated with increasing weight (r = 0.30, P < 0.001) and reduced quadriceps strength (r = –0.37, P = 0.002). Conclusion: Compared with age and sex‐matched controls, females with symptomatic knee OA have reduced knee proprioception, balance responses and quadriceps strength.     

Physical activity and functional abilities in adult males with haemophilia: a cross‐sectional survey from a single US haemophilia treatment centre

Physical activity and functional ability are important determinants of quality of life and these metrics are affected by both haemophilia and ageing. Outside haemophilic arthropathy, risk factors leading to reduced physical activity and function in people with haemophilia (PWH) are under‐explored. The purpose of this analysis was to determine risk factors for reduced physical activity and functional limitations in PWH. A secondary analysis was conducted on data indexing physical activity and functioning of 88 PWH using data originally collected as part of a cross‐sectional study at a single large haemophilia treatment centre. The Framingham Physical Activities Index (PAI), the Hemophilia Activities List (HAL) and the Timed Up‐and‐Go Test (TUG) were the outcome measures. The World Federation of Haemophilia (WFH) orthopaedic joint score was used as a measure of arthropathy. Multiple linear regression analysis was used to assess the relationship between the outcome measures and covariates. Worsening WFH joint score was independently associated with all three outcome measures (P < 0.05). Increasing age was associated with reduced PAI and increased TUG time (P < 0.05). The HAL summary score was decreased in patients with chronic liver disease (P = 0.006). The adjusted R² for each model was ≤0.35. This study provides evidence for the relationship between arthropathy and reduced physical functioning/activity, but also highlights that much of the variation in physical functioning/activity is not explained by haemophilia‐related characteristics.     

Obesity in haemophilia patients: effect on bleeding frequency,clotting factor concentrate usage,and haemostatic and fibrinolytic parameters

The prevalence of obesity in patients with haemophilia (PWH) is increasing. We investigated the effect of obesity on bleeding frequency and clotting factor concentrate (CFC) usage in PWH and assessed whether prothrombotic changes observed in obesity differ between controls and PWH. Number of bleeds and CFC usage were compared between obese (N = 51) and non‐obese (N = 46) haemophilia A patients. Markers of haemostasis and fibrinolysis were compared between PWH, and gender‐, age‐ and body mass index (BMI)‐matched non‐haemophilic controls (N = 91). Median number of bleeds/patient‐month was comparable between obese and non‐obese patients with severe haemophilia (P = 0.791). Obese patients with severe haemophilia used 1.4 times more CFC/patient‐month than non‐obese patients (P = 0.036). When adjusting for weight this difference disappeared (P = 0.451). von Willebrand factor plasma concentration (VWF:Ag), factor VIII activity and endogenous thrombin potential were higher in obese than in non‐obese controls. Obesity did not influence these markers in PWH. Plasminogen activator inhibitor type 1 levels were higher in obese vs. non‐obese PWH (P < 0.001), whereas levels were comparable between PWH and controls (P = 0.912). Plasmin‐α2‐antiplasmin complex (PAP) levels appeared to be lower in obese vs. non‐obese subjects, both within controls (P = 0.011) and PWH (P = 0.008). However, in PWH, PAP levels were higher than in controls (P < 0.001). Obesity is associated with an increase in net CFC usage in PWH, but has no effect on bleeding frequency. In addition, obesity attenuates hyperfibrinolysis in PWH. Future research investigating whether obese PWH need CFC treatment dosed on weight or whether a lower dosage would suffice to prevent and treat bleedings is needed.     

A longitudinal study of family structure in Swedish persons with haemophilia

Haemophilia is an X‐linked inherited rare bleeding disorder affecting mainly men. The treatment consists of replacement therapy that has been associated with severe side effects, such as blood transmitted viral infections, but has markedly improved over the last decades. The aim of this study was to study family structure over time among Swedish persons with haemophilia (PWH), focusing on children, siblings and marital status. PWH A or B were identified from the haemophilia centres and the national Patient Registry. Each PWH was compared to five age‐ and gender‐matched controls. The national Multi‐Generation Registry was used to identify children and siblings. A total of 1365 children with a father suffering from haemophilia A or B and 1938 siblings of the PWH were identified. Having one or more children was significantly less common (P = 0.003) for PWH than for controls. Significantly lower rates of having a child were also found for the subgroups of persons suffering from severe haemophilia and those infected with HIV (P < 0.001). A higher proportion of PWH, with or without HIV and/or viral hepatitis had siblings compared to the controls (P < 0.001). However, the mean number of siblings was significantly lower for persons with severe haemophilia (P = 0.001). The number of marriages and divorces did not differ between PWH and controls. Our data indicate a negative impact of HIV and viral hepatitis on family structure for PWH despite the relatively good access to treatment in Sweden over the last few decades. This was particularly true for those with a severe form of haemophilia.     

Risk assessment for coronary heart disease in patients with haemophilia: a single centre study in the United States

In haemophilia, coronary heart disease (CHD) occurs at a similar frequency as in the general population, but the contributing risk factors in haemophilia are incompletely understood. To investigate risk factors and 10‐year CHD risk in a single centre cohort of patients with haemophilia (PWH) ≥20 years old (n = 89). We retrospectively applied the modified Framingham National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP) III risk prediction equation. Three risk levels were defined: <10% (low), 10–20% (intermediate) and >20% (high). Results were compared to the National Health and Nutrition Examination Survey (NHANES). Mean age in both cohorts was similar. Compared to NHANES, systolic blood pressures were significantly higher in PWH, but current smoking and cholesterol were lower. CHD risk differed significantly between PWH and NHANES (P = 0.005) with a higher proportion of PWH classified at low risk (77.5% vs. 61.0%). The proportion of low risk patients was also significantly higher for severe haemophilia patients compared to non‐severe haemophilia patients (88.6% vs. 66.7%, P = 0.02). Among PWH, and compared to PWH who were hepatitis C (HepC) negative, HepC positive patients had significantly lower cholesterol, LDL and triglycerides. The CHD risk of HepC positive patients differed significantly from NHANES (P = 0.03) with a lower proportion of HepC positives being classified as high risk (5.7% vs. 17.3%). Favourable CHD risk classification in PWH may be influenced by low cholesterol associated with HepC infection. Estimates of CHD risk in PWH by composite scoring may not be accurate and will require studies correlating risk factors with incident CHD.     

Balance dysfunction in adults with haemophilia

Summary. The main focus of lower limb physical performance assessment in people with haemophilia (PWH) has usually been on function, muscle strength and joint flexibility. The impact of haemophilic arthropathy on balance and falls risk is relatively under‐explored. The aim of this study was to evaluate balance and related performance in PWH compared with age and gender matched healthy controls. It involved a comprehensive suite of clinical and laboratory measures of static and dynamic balance, mobility, strength, physical activity and falls efficacy completed in 20 PWH (mean age 39.4, 100% male) and 20 controls. Fifty percent of PWH reported falls in the past 12 months. Moderate impairment of balance and related measures were identified in PWH compared with the controls, with an average 35% difference between groups. Significant differences were evident between groups on both clinical and laboratory measures, including measures of dynamic bilateral stance balance [limits of stability measures on the laboratory test, functional reach; (P < 0.001); dynamic single leg balance (Step Test, P < 0.001)], gait and mobility (gait speed, step width and turning measures on the laboratory test, timed up and go test; P < 0.001); muscle strength (timed sit to stand, P = 0.002; quadriceps strength, P < 0.001); and activity level and falls efficacy, (P < 0.004). The dynamic clinical and laboratory measures testing similar domains of balance, gait and mobility had moderate correlations (0.310 < r < 0.531, P < 0.01). Moderate impairments in balance, mobility and related measures were identified in PWH, compared with the control group. Clinicians should include assessments of balance and related measures when reviewing adults with haemophilia.     

Self‐monitoring has potential for home exercise programmes in patients with haemophilia

Haemophiliacs who have had to keep a physically inactive lifestyle due to bleeding during childhood are likely to have little motivation for exercise. The purpose of this study is to clarify the effectiveness of the self‐monitoring of home exercise for haemophiliacs. A randomized controlled trial was conducted with intervention over 8 weeks at four hospitals in Japan. Subjects included 32 male outpatients aged 26–64 years without an inhibitor who were randomly allocated to a self‐monitoring group and a control group. Individual exercise guidance with physical activity for improvement of their knee functions was given to both groups. The self‐monitoring materials included an activity monitor and a feedback system so that the self‐monitoring group could send feedback via the Internet and cellular phone. The self‐monitoring was performed by checking exercise adherence and physical activity levels, bleeding history and injection of a coagulation factor. Both groups showed significant improvements in exercise adherence (P < 0.001) and physical function such as the strength of knee extension (P < 0.001), range of knee extension (P < 0.001), range of ankle dorsiflexion (P < 0.01), a modified Functional Reach (P < 0.05) and 10 metre gait time (P < 0.01). In particular, improvements in exercise adherence (P < 0.05), self‐efficacy (P < 0.05), and strength of knee extension (P < 0.05) were significant in the self‐monitoring group compared with those in the control group. No increase in bleeding frequency and pain scale was noted. The self‐monitoring of home exercise for haemophilic patients is useful for the improvement of exercise adherence, self‐efficacy and knee extension strength.     

Addition of Novel Biomarkers for Predicting All‐Cause and Cardiovascular Mortality in Prevalent Hemodialysis Patients

Novel biomarkers might improve the prediction of mortality in hemodialysis (HD) patients. We simultaneously measured the levels of conventional and novel biomarkers [serum N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), intact fibroblast growth factor‐23 (FGF23), β2‐microglobulin (β2MG), cystatin C, and high‐sensitivity C‐reactive protein (hsCRP)] in 307 prevalent Japanese HD patients. There were 66 all‐cause deaths, and 25 cardiovascular (CV) deaths during 2 years, which were assessed using Cox models and concordance (C)‐statistics. The addition of NT‐proBNP alone (P < 0.05) or NT‐proBNP, hsCRP, and β2MG as a panel (C‐statistics: 0.834 vs. 0.776, P < 0.01) to a conventional risk model composed of age, diabetes, and the serum albumin level significantly improved the prediction of 2‐year all‐cause mortality, and the addition of NT‐proBNP and hsCRP as a panel to a conventional risk model composed of age significantly improved the prediction of 2‐year CV mortality (P < 0.05) in Japanese prevalent HD patients. Neither FGF23 nor cystatin C improved mortality prediction.     

Incidence and survival of cancers among 1,054 hemophilia patients: A nationwide and 14‐year cohort study

As life expectancy increases in persons with hemophilia (PWH), more age‐related diseases such as cancer emerge among this patient group. The aim of this study was to investigate incidence and survival of cancers among PWH in Taiwan. We analyzed data of 1,054 PWH retrieved from Taiwan's National Health Insurance Research Database between 1997 and 2010, by comparing variables to 10540 age‐ and gender‐matched healthy individuals from the general population. There were 43 PWH and 178 individuals of general population with newly diagnosed cancer (RR 2.42, 95% CI 1.74–3.35). The cumulative incidences of cancer in PWH and the general population were 4.7 and 1.9%, respectively. Hepatocellular carcinoma (HCC) was the major type of cancer (17 cases) in PWH; cancer rate was still increased when HCC and HIV‐related cancers were excluded (RR 1.66, 95% CI 1.06–2.59). There was no significant difference observed in lung, colorectal, or prostate cancer occurrence. Compared to the general population, PWH were younger at the time of cancer diagnosis (45.1 vs. 57.2 years old, P value < 0.001), and had fewer co‐morbidities. Nineteen PWH with cancers died during the study period, and no bleeding‐related death was recorded among these patients. The survival rate was not different between PWH and the general population, P = 0.86. In conclusion, the cumulative incidence of cancer among PWH was higher than the general population. PWH with cancer were younger and had fewer comorbidities, but the survival rates were similar in the two groups.Am. J. Hematol. 90:E55–E59, 2015. © 2015 Wiley Periodicals, Inc.     

Muscle strength,functional performance,and self‐reported outcomes four years after arthroscopic partial meniscectomy in middle‐aged patients

Objective

To examine thigh muscle strength, functional performance, and self‐reported outcome in patients with nontraumatic meniscus tears 4 years after operation, and to study the impact of a strength deficit on self‐reported outcome and evaluate the feasibility of 3 performance tests in this patient group.

Methods

The study group comprised 45 patients (36% women, mean age 46.7) who had an arthroscopic partial meniscectomy a mean of 4 years (range 1–6 years) previously. Main outcome measures included isokinetic strength of knee extensors and flexors, functional performance (1‐leg hop, 1‐leg rising, and square‐hop tests), and a self‐reported questionnaire (Knee Injury and Osteoarthritis Outcome Score).

Results

We found lower knee extensor strength and worse 1‐leg rising capacity in the operated leg, but no difference between operated and nonoperated leg for knee flexors (P ≤ 0.004 and P > 0.3, respectively). Patients with a stronger quadriceps of the operated leg compared with the nonoperated leg had less pain and better function and quality of life (r = 0.4–0.6, P ≤ 0.010). We found the 1‐leg rising and 1‐leg hop tests to be suitable performance tests in middle‐aged meniscectomy patients.

Conclusion

Quadriceps strength is reduced in the meniscectomized leg compared with the nonoperated leg 4 years after surgery. This relative quadriceps weakness significantly affects objective and self‐reported knee function, pain, and quality of life, indicating the importance of restoring muscle function after meniscectomy in middle‐aged patients.

     

Influence of ankle plantar flexor muscle architecture and strength on gait in boys with haemophilia in comparison to typically developing children

Altered gait patterns, muscle weakness and atrophy have been reported in young boys with severe haemophilia when compared to unaffected peers. The aim of this study was to determine whether lateral gastrocnemius muscle size and architecture influenced biomechanical walking patterns of boys with haemophilia and if these relationships differed from age‐matched typically developing boys. Biomechanical function of the knee and ankle during level walking, lateral gastrocnemius anatomical cross‐sectional area, thickness, width, fascicle length and pennation angle and ankle plantar flexor muscle strength were recorded in 19 typically developing boys aged 7–12 years and 19 age‐matched haemophilic boys with a history of ankle joint bleeding. Associations between gait, strength and architecture were compared using correlations of peak gait values. Haemophilic boys walked with significantly larger (P < 0.05) ankle dorsi flexion angles and knee flexion moments. The ankle plantar flexor muscles of haemophilic boys were significantly weaker and smaller when compared to typically developing peers. In the typically developing boys there was no apparent association between muscle architecture, strength and walking patterns. In haemophilic boys maximum muscle strength and ACSA normalized torque of the ankle plantar flexors together with the muscle width, thickness, fascicle length and angulation (P < 0.05) were associated with motion at the ankle and peak moments at the knee joint. Muscle strength deficits of the ankle plantar flexors and changes in muscle size and architecture may underpin the key biomechanical alterations in walking patterns of haemophilic boys with a history of ankle joint bleeding.     

Baseline Lower Extremity Strength and Subsequent Decline in Functional Performance at 6‐Year Follow‐Up in Persons with Lower Extremity Peripheral Arterial Disease

OBJECTIVES: To evaluate associations between baseline lower extremity strength and decline in functional performance over 6 years of follow‐up in men and women with lower extremity peripheral arterial disease (PAD). DESIGN: Prospective observational study. SETTING: Three Chicago‐area hospitals. PARTICIPANTS: Three hundred seventy‐four men and women with PAD. MEASUREMENTS: Baseline isometric hip extension, hip flexion, knee flexion, and knee extension strength were measured using a musculoskeletal fitness evaluation chair. Usual and fastest‐paced 4‐m walking speed, 6‐minute walk, and Short Physical Performance Battery (SPPB) were assessed at baseline and annually thereafter. Analyses were adjusted for age, sex, race, ankle–brachial index (ABI), comorbidities, and other confounders. RESULTS: In women with PAD, weaker baseline hip and knee flexion strength were associated with faster average annual decline in usual‐pace 4‐m walking speed (P trend <.001 and .02, respectively) and SPPB (P trend=.02 and .01, respectively). In women, weaker hip extension strength was associated with faster decline in usual‐pace 4‐m walking speed and SPPB (P trend=.01 and <.01, respectively). There were no significant associations between baseline strength and decline in 6‐minute walk in women. There were no significant associations between any baseline strength measure and functional decline in men. CONCLUSION: Weaker baseline leg strength is associated with faster functional decline in nonendurance measures of functional performance in women with PAD but not in men with PAD.     

Can motor proficiency testing predict sports injuries and sports-induced bleeds in people with haemophilia?

Introduction

Predicting the risk of sports injuries and sports-induced bleeds (SIBs) in people with haemophilia (PWH) may support clinical counselling.

Aim

To assess the association between motor proficiency testing and sports injuries and SIBs and to identify a specific set of tests for predicting injury risk in PWH.

Methods

In a single centre, prospective study male PWH aged 6–49 playing sports ≥1x/week were tested for running speed and agility, balance, strength and endurance. Test results below −2Z were considered poor. Sports injuries and SIBs were collected for 12 months while 7 days of physical activity (PA) for each season was registered with accelerometers. Injury risk was analysed according to test results and type of physical activity (%time walking, cycling, running). Predictive values for sports injuries and SIBs were determined.

Results

Data from 125 PWH (mean [± SD] age: 25 [± 12], 90% haemophilia A; 48% severe, 95% on prophylaxis, median factor level: 2.5 [IQR 0–15]IU/dl) were included. Few participants (n = 19, 15%) had poor scores. Eighty-seven sports injuries and 26 SIBs were reported. Poor scoring participants reported 11/87 sports injuries and 5/26 SIBs. The current tests were poor predictors of sports injuries (Range PPV: 0%–40%), or SIBs (PPV: 0%–20%). PA type was not associated with season (activity seasonal p values > .20) and type of PA was not associated with sports injuries or SIBs (Spearman's rho < .15).

Conclusion

These motor proficiency- and endurance tests were unable to predict sports injuries or SIBs in PWH, potentially due to few PWH with poor results and low numbers of sports injuries and SIBs.     

Presentation and management of acute coronary syndromes among adult persons with haemophilia: results of an international,retrospective, 10‐year survey

Sparse data are available on presentation and management of acute coronary syndromes (ACS), including unstable angina and non‐ST‐ and ST‐elevation myocardial infarction, among persons with haemophilia (PWH). The aim of this study was to determine demographics, bleeding disorder characteristics, cardiovascular risk factors (CRFs), interventions, haemostatic protocol, revascularization outcomes and complications among PWH with ACS. Members of an international consortium comprising >2000 adult PWH retrospectively completed case report forms for episodes of ACS in a >10‐year follow‐up period (2003–2013). Twenty ACS episodes occurred among 19 patients [rate, 0.8% (95% CI 0.4, 1.2)]. Seven patients (37%) were aged <50 years; 10 (53%) had ≥3 CRFs. In 5/20 episodes (25%), the initial ACS management protocol was altered because of the bleeding disorder. None of the eight patients with severe haemophilia underwent coronary artery bypass grafting (CABG), compared with 54.5% of patients with non‐severe disease (P = 0.02). Revascularization with percutaneous coronary intervention (PCI) or CABG was rated successful in 13/13 cases, with no excessive bleeding during initial management. During chronic exposure to antiplatelet agents, secondary haemophilia prophylaxis was more prevalent in patients with severe haemophilia compared with non‐severe haemophilia (85.7% vs. 30%, P = 0.05). No ACS‐related deaths occurred during initial management, but one patient with severe haemophilia A died of undetermined cause 36 months after the ACS event while on aspirin therapy. ACS occurs even among relatively younger PWH, typically in association with multiple CRFs. Revascularization with PCI/CABG is feasible, and antiplatelet agents plus secondary prophylaxis appears to be well tolerated in selected PWH with ACS.     

Skeletal Muscle Loss Is Negatively Associated With Single‐Pool Kt/V and Dialysis Duration in Hemodialysis Patients

We evaluated the skeletal muscle loss in hemodialysis (HD) patients by bioelectrical impedance analysis (BIA) and handgrip strength test. Thirty‐four HD patients and 16 healthy subjects (control group) were measured for skeletal muscle mass normalized as the skeletal muscle mass index (SMI), calculated as skeletal muscle mass (kg)/height (m)² using a tetrapolar bioelectrical impedance plethysmograph. Handgrip strength test was also performed using a hand dynamometer in both groups. In HD patients, the associations of SMI and handgrip strength with age, sex, HD conditions, and HD parameters such as body mass index (BMI), single‐pool Kt/V (spKt/V), normalized protein catabolic rate (nPCR), creatinine generation rate (CGR) and serum albumin level (Alb) were investigated. SMI of HD patients (4.58 ± 0.95 kg/m²) was significantly lower than that of the control group (5.55 ± 0.80 kg/m², P < 0.01). The handgrip strength of HD patients (19.9 ± 7.74 kg) was also significantly lower than that of the control group (33.0 ± 8.94 kg, P < 0.01). In HD patients, HD duration was associated with both SMI and handgrip strength. Among HD parameters, spKt/V was negatively associated with both SMI and handgrip strength, BMI and Alb were positively associated with SMI, while nPCR and CGR were associated with neither SMI nor handgrip strength. HD duration independently contributed to skeletal muscle loss and the value of spKt/V may be affected by skeletal muscle loss in HD patients.     

Upper Limb Disability in Hemodialysis Patients: Evaluation of Contributing Factors Aside From Amyloidosis

This cross‐sectional case‐control study evaluated upper limb muscle strength and shoulder mobility in hemodialysis (HD) patients with arteriovenous fistula or graft. Twenty‐five adult patients on thrice‐a‐week HD treatment for 6 months at least, were selected for the study. In all the patients and control subjects, handgrip tests and tests of range of motion in the upper extremities were evaluated by physiotherapy tests. Patients on HD showed lower muscle strength than age and sex matched subjects without severe chronic kidney disease (right: 30.1 ± 11.6 vs 40.5 ± 15.1 kg, P < 0.001; left 29.1 ± 12.9 vs 40.7 ± 11.1 kg, P < 0.01), and a reduced range of shoulder mobility. The presence of fistula or graft was associated with a greater limitation of both active (74.0 ± 18.3 vs 85.2 ± 8.8 °, P < 0.01) and passive (82.2 ± 9.9 vs 87.2 ± 6.6 °, P < 0.05) extra‐rotation than the contralateral limb, with a higher prevalence of impingement (72 vs 36%, P < 0.05). Muscle strength was related to albumin and inversely to age; whereas β₂‐microglobulin and CRP serum levels were associated with impairment of passive and active extra‐rotation of the shoulder that was free from the fistula or graft. In summary, patients on HD have a reduced range of shoulder mobility and marked reduction of muscle strength. The abnormalities are more prevalent in upper limbs with fistula or grafts. The arteriovenous fistula or graft may worsen the disability of the patient's upper limbs presumably due to the obligate position required during the HD sessions. Proper pre‐ and post‐dialysis exercise programs should be implemented to maintain mobility and strength of the upper limbs.     

Haemophilia & Exercise Project (HEP): The impact of 1‐year sports therapy programme on physical performance in adult haemophilia patients

Episodes of bleeding in people with haemophilia (PWH) are associated with reduced activity and limitations in physical performance. Within the scope of the ‘Haemophilia & Exercise Project’ (HEP) PWH were trained in a sports therapy programme. Aim of this study was to investigate subjective and objective physical performance in HEP‐participants after 1 year training. Physical performance of 48 adult PWH was compared before and after sports therapy subjectively (HEP‐Test‐Q) and objectively regarding mobility (range of motion), strength and coordination (one‐leg‐stand) and endurance (12‐min walk test). Sports therapy included an independent home training that had previously been trained in several collective sports camps. Forty‐three controls without haemophilia and without training were compared to PWH. Of 48 PWH, 13 performed a regular training (active PWH); 12 HEP‐participants were constantly passive (passive PWH). Twenty‐three PWH and 24 controls dropped out because of incomplete data. The activity level increased by 100% in active PWH and remained constant in passive PWH, and in controls (P ≤ 0.05). Only mobility of the right knee was significantly improved in active PWH (+5.8 ± 5.3°) compared to passive PWH (?1.3 ± 8.6°). The 12‐min walk test proved a longer walking distance for active PWH (+217 ± 199 m) compared to controls (?32 ± 217 m). Active PWH reported a better subjective physical performance in the HEP‐Test‐Q domains ‘strength & coordination’, ‘endurance’ and in the total score (+9.4 ± 13.8) compared to passive PWH (?5.3 ± 13.5) and controls (+3.7 ± 7.5). The ‘mobility’‐scale and one‐leg‐stand remained unchanged. Sports therapy increases the activity level and physical performance of PWH, whereby objective effects do not always correspond with subjective assessments.     

GWAS identifying HLA‐DPB1 gene variants associated with responsiveness to hepatitis B virus vaccination in Koreans: Independent association of HLA‐DPB1*04:02 possessing rs1042169 G ‐ rs9277355 C ‐ rs9277356 A

Recently, HLA class II loci, including HLA‐DPB1, have been reported to be associated with interindividual variance in the hepatitis B (HB) vaccine response. In this study, we investigated significant single nucleotide polymorphisms (SNPs) for anti‐HBs antibody levels in 6867 healthy Koreans using a genome‐wide association study (GWAS). In GWAS, the top 20 SNPs that showed significant association with anti‐HBs levels (P < 1.0 × 10^?29) all resided in HLA‐DPB1. Utilizing PCR sequencing, we verified the relationship of the top 3 most significant SNPs (rs1042169, rs9277355 and rs9277356) from the GWAS and genotypes of HLA‐DPB1 with the HB vaccine response in Korean infants who received a scheduled vaccination. The DPB1*04:02 allele has G, C and A nucleotides for the 3SNP sites, and was significantly more frequent in responders than in nonresponders (10.9% vs 1.0%, P_c = 0.018). DPB1*05:01 was significantly more frequent in nonresponders than in responders (49.0% vs 31.1%, P_c = 0.018). In multivariate logistic regression, DPB1*04:02 showed a significant association with both vaccine response (P = 0.037, OR = 8.465) and high‐titre response (P = 0.027, OR = 9.860). The haplotypes rs1042169 G ‐ rs9277355 C ‐ rs9277356 A showed a significant association with a high‐titre response only (P = 0.002, OR = 2.941). In conclusion, DPB1*04:02 possessing rs1042169 G ‐ rs9277355 C ‐ rs9277356 A is an independent predictor of the HB vaccine response in Koreans.     

Haemophilia & Exercise Project (HEP): subjective and objective physical performance in adult haemophilia patients – results of a cross‐sectional study

Summary. Recurrent musculoskeletal haemorrhages in people with haemophilia (PWH) lead to restrictions in the locomotor system and consequently in physical performance. Patients’ perceptions of their health status have gained an important role in the last few years. The assessment of subjective physical performance in PWH is a new approach. This study aimed to compare the subjective physical performance of PWH with healthy controls and to correlate the results with objective data. Subjective physical performance was assessed via the new questionnaire HEP‐Test‐Q, which consists of 25 items pertaining to four subscales ‘mobility’, ‘strength & coordination’, ‘endurance’ and ‘body perception’. HEP‐Test‐Q subscales were compared with objective data in terms of range of motion, one‐leg‐stand and 12‐minute walk test. Forty‐eight patients (44 ± 11 years) with haemophilia A (43 severe, three moderate) or B (two severe) and 43 controls without haemophilia (42 ± 11 years) were enrolled. PWH showed an impaired subjective physical performance in all HEP‐Test‐Q subscales and in the total score (52 ± 20) compared with controls (77 ± 10; P ≤ 0.001). Correlation analyses for the total score of the HEP‐Test‐Q and objective data revealed values ranging from r = 0.403 (one‐leg‐stand) to r = 0.757 (12‐minute walk test) (P ≤ 0.001). PWH evaluated their physical performance poorer in comparison with healthy people. As self‐assessment did not always correlate highly with objective data, objective examinations of physical performance in PWH should be complemented with subjective perceptions.