Safety and Effectiveness of Progressive Moderate-to-Vigorous Intensity Elastic Resistance Training on Physical Function and Pain in People With Hemophilia.

OBJECTIVE: Strength training is recommended for people with hemophilia; however, published data are anecdotal and have methodological limitations. The purpose of this study was to evaluate the safety and effectiveness of progressive moderate-to-vigorous intensity elastic resistance training on physical function and pain in this patient population. METHODS: A randomized controlled trial was conducted in a university laboratory setting where 20 patients (17 with severe, 1 with moderate, and 2 with mild hemophilia) aged 21 to 53 years received evaluations at baseline and 8-week follow-up. Participants were allocated to intervention (progressive strength training) or control (usual daily activities) groups. The intervention group trained 2 days per week during 8 weeks with elastic resistance. Intensity during the first 2 weeks was a 20-repetition maximum and increased progressively toward 15, 12, and finally 10 repetition maximum. The primary outcome was muscle strength. Secondary outcomes were the Timed "Up and Go" Test score, sit-to-stand, range of motion, Haemophilia Joint Health Score, kinesiophobia score, global impression of pain change, general self-rated health status, and desire to exercise. RESULTS: The intervention group showed greater strength improvements than the control group in almost all of the joints, with moderate to high effect sizes. The intervention group also showed better Timed "Up and Go" and sit-to-stand scores than the control group (moderate effect size), greater range of motion at the knee flexion with the right leg (trivial effect size), and better Haemophilia Joint Health Score at the left knee (small effect size). The intervention group showed greater overall pain reduction, self-rated overall status, and desire to exercise than the control group. CONCLUSIONS: Progressive strength training with elastic resistance performed twice a week during 8 weeks is safe and effective in people with hemophilia to improve muscle strength and functional capacity, reduce general pain, and improve self-rated health status and desire to exercise. IMPACT: This study provides evidence for the use of a specific strength training regimen for people with hemophilia. LAY SUMMARY: People with hemophilia of differing levels of severity, with adequate coverage with clotting factor, can safely engage in progressive strength training and can improve their functioning.

Telemedicine and telerehabilitation: current and forthcoming applications in haemophilia.

In persons with haemophilia (PWH), the importance of comprehensive disease management to prevent bleeding, joint damage and secondary diseases has been well established. However, because haemophilia is a chronic disease, intervention programmes carried out for prolonged periods of time may create problems of patient adherence. Driven by continuous technological innovation, telemedicine is being increasingly proposed as a way to provide PWH with a range of services designed to improve their health, saving the time and cost involved in going to the treatment centre, and increasing therapeutic adherence. The aim of this article is to identify and discuss the tools available for the management of PWH by means of telemedicine and information technology. Video conferences are helpful to obtain a rapid evaluation at a distance of the occurrence and severity of bleeding episodes by the personnel of the treatment centre. Cell phones and associated applications (apps) help to improve the regular implementation of replacement therapy and monitor any ensuing adverse effect. Portable sensors help to improve lifestyle and to monitor the degree of physical activity through the fulfilment of a given number of daily walking steps and other physical activities. In the context of telerehabilitation, exergames have the potential to improve the musculoskeletal function of PWH by exploiting the recreational features of videogames. Thus, telemedicine and its multiple applications may be useful in the management of haemophilia, especially for patients living far from specialised centres. However, since this is a recent and rapidly evolving field, published studies are few and have, so far, involved only a limited number of cases. Therefore, additional evidence needs to be obtained by means of accrual of cumulative data from multiple centres specialised in haemophilia.

Health promotion for young patients with haemophilia.

The haemophilia treatment centre of the Clinic for Children and Youth Medicine in Jena extends medical care by health-promotion measures, namely: health counselling, adjuvant exercise therapy and school sports. In addition to the regular medical checks at the treatment centre patients are examined regarding physical fitness, joint situation, quality of life in general and disease-specific manner, as well as psycho-social and nutritional behaviour. Findings and medical results of the examinations are integrated into an individual advice on therapy, school sports, and health recommendations. This aimed at strengthening health-related resources and minimizing potential injuries. First long-term evaluation shows an increase of activity behaviour and physical fitness without increasing bleeding rate and maintained joint function. CONCLUSION: Combining functional prevention diagnostics and individual health counselling shows signs of improved patient's health knowledge, self-competence and physical fitness.

Follow-up of a 6-month Programmed Sports Therapy (PST) in patients with haemophilia.

Studies describe benefits of exercise in Patients with haemophilia (PwH), but research on training sustainability is rare. Aim of this study was to observe the follow-up of a guided 6-month training intervention in PwH. This study included 28 PwH after a training intervention (RCT) over 6 months. N=17 continued training (TC), N=11 stopped training (TS) after the study time. Strength measurements and subjective physical performance were tested.The RCT revealed that all muscles tested increased significantly after training. In the follow-up phase, the muscles of TC increased further (in TS decreased), but not all of them significantly (M. triceps brachii: p=0.017; M. biceps brachii: n.s.; M. latissimus dorsi: n.s.; M. rectus abdominis: p=0.002; M. biceps femoris right: n.s.; left: p=0.028; M. quadriceps femoris both n.s. = not sig.). Subjective performance showed no clear changes in the follow-up phase.This is the first study evaluating a follow-up phase of programmed sports therapy (PST) in PwH. PST (6-month) resulted in some PwH continuing the successful training. Benefits were training routine, safety and partially further positive training effects, e.g. in strength performance.

Exercise for haemophilia.

BACKGROUND: Haemophilia is a bleeding disorder associated with haemorrhaging into joints and muscles. Exercise is often used to aid recovery after bleeds, and to improve joint function in the presence of arthropathy. OBJECTIVES: Our objective was to systematically review the available evidence on the safety and effectiveness of exercise for people with haemophilia. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register and electronic databases PubMed, OVID-Embase, and CINAHL. We hand searched abstracts from congresses of the World Federation of Hemophilia and the European Hematology Association, trial registries and the reference lists of relevant articles.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 14 December 2016. SELECTION CRITERIA: Randomized or quasi-randomized controlled studies comparing any exercise intervention considered relevant in haemophilia management including supervised, unsupervised, aquatic, strengthening, aerobic or cardiovascular, stretching, proprioceptive and balance training exercise programs in males of any age with haemophilia A or B of any severity (those with co-morbidities were not excluded). DATA COLLECTION AND ANALYSIS: Two authors reviewed the identified abstracts to determine their eligibility. For studies meeting the inclusion criteria, full articles were obtained. The two authors extracted data and assessed the risk of bias. Any disagreements were resolved by discussion. The authors contacted study investigators to obtain any missing data. MAIN RESULTS: Eight studies were included, which represented 233 males with all severities of haemophilia A and B, ranging in age from eight years to 49 years. Study duration ranged from four to 12 weeks. Exercise interventions varied greatly and included resistance exercises, isometric exercises, bicycle ergometry, treadmill walking and hydrotherapy; therefore, comparison between studies was difficult.None of the studies measured or reported adverse effects from the interventions. None of the studies reported outcomes regarding bleed frequency, quality of life or aerobic activity. Overall risk of bias across all studies was assessed as unclear.Very few studies provided sufficient information for comparison. None of the studies reported data that favoured the control group. One study reported that six weeks of resistance training improved joint health status (Colorado score) compared to controls. The addition of pulsed electromagnetic fields also improved ankle scores compared to exercises alone, but this was not seen in the elbows or knees.Two studies reported statistically significant improvements in pain intensity after exercise interventions compared to controls. Hydrotherapy exercises produced significant decreases in pain compared to controls and land-based exercise groups.Two studies found improvement in joint motion in the exercise group compared to controls. One study compared land- and water-based exercises; there was no difference in the range of motion between the two groups; however, the water-based exercise group did show improvement over the control group.One study, comparing joint traction and proprioceptive neuromuscular facilitation for the elbow to a control group, showed no differences in biceps girth or strength after 12 weeks of intervention.Some studies reported comparisons between interventions. In one study, treadmill training significantly improved balance in children compared to bicycle ergometry. Another study added partial weight bearing exercises to quadriceps exercises and showed improved walking tolerance.Four studies evaluated quadriceps or hamstring strength (or both). The addition of bicycle ergometry and exercises with weights was more effective than static exercises and treadmill walking for strengthening knee flexors and extensors. Partial weight-bearing exercises through range were more effective than static and short arc exercises for improving knee extensor strength. The addition of treadmill walking to ultrasound, stretching and strengthening exercises showed increased peak torque of knee flexors and extensors and decrease in knee effusion.The results should be interpreted with caution due to the quality of evidence (GRADE) as outlined in the summary of findings tables, which demonstrates that all but one of the outcomes assessed were rated as low or very low due to the small sample sizes and potential bias. AUTHORS' CONCLUSIONS: These results must be considered with caution. There is a lack of confidence in the results due to the small number of included studies and the inability to pool the results due to the heterogeneity of outcome measures. Most exercise interventions produced improvement in one or more of the measured outcomes including pain, range of motion, strength and walking tolerance. Hydrotherapy may be more effective than land exercises for pain relief in adults. Functional exercises such as treadmill walking and partial weight bearing exercises seem to be more effective than static or short arc exercises for improving muscle strength. These findings are consistent with the many non-controlled intervention reports in the haemophilia literature. No adverse effects were reported as a result of any of the interventions. However, some groups used prophylactic factor prior to exercise and other groups studied only subjects with moderate haemophilia. Therefore, the safety of these techniques for persons with severe haemophilia remains unclear.

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.

Effectiveness of a balance training home exercise programme for adults with haemophilia: a pilot study.

Adults with haemophilia and other bleeding disorders often develop lower limb musculoskeletal problems associated with bleeds into joints and muscles, which may affect balance performance and increase likelihood of falling. The aim of this study was to evaluate the effectiveness of an individualized balance and strength home exercise programme on improving balance and related outcomes for adults with haemophilia and other bleeding disorders. Twenty male adults with haemophilia and other bleeding disorders (mean age 39.4 years, 95% CI = 33.7-45.1) were recruited to participate. They underwent a comprehensive clinical and force platform assessment of balance and related measures. Based on assessment findings, the assessing physiotherapist provided an individualized home exercise programme of balance, strengthening and walking exercises. Re-assessment occurred after the 4-month exercise programme. Twelve participants (60%) completed the programme and were re-assessed. There were no safety problems or dropouts associated with the exercise programme aggravating joint status. Although there were no statistically significant changes in any of the measures (adjusted for multiple comparisons), there were improvements of between 5% and 22% on 10 of the 16 measures, with the Neurocom modified Clinical Test of Sensory Interaction on Balance (P = 0.036) and Timed Sit to Stand (P = 0.064) approaching significance. A tailored home exercise programme targeting balance, strengthening and walking is feasible for adults with haemophilia and other bleeding disorders. These results suggest that positive physical outcomes including improved balance and mobility may be achieved with this type of programme.

Oral and general health-related quality of life among young patients with haemophilia.

The clinical diagnosis of dental diseases may indicate their cause and prognosis, however it gives little information about resulting levels of impairment from the patients' perspective. In this study, we aimed to investigate oral and general health-related quality of life (OHRQoL-HRQoL) in patients with haemophilia; and to test whether haemophiliacs would have worse or better OHRQoL compared with the general population. Data were collected from haemophiliacs (age range 14-35; mean 23 +/- 6.58, n = 71) and age/sex-matched controls (age range 14-35; mean 21.00 +/- 6.45, n = 60) through face-to-face interviews including nine questions and using oral health impact profile (OHIP)-14, oral health-related quality of life-UK (OHQoL-UK), short-form general measure of health (SF)-36 to measure self-rating oral health status, perceived dental treatment needs, tooth brushing frequencies, OHRQoL-HRQoL. In the field of self-rating oral health status, perceived dental treatment needs, tooth brushing frequencies and OHIP, OHQoL-UK, SF-36 scores - except the subscales including vitality, role emotional and mental health - the control group is in better conditions compared with the haemophilia group. At the same time, both the two groups are in good conditions in dental attendance, vitality, role emotional and mental health. Life quality is related with the perceived discrepancy between the reality of what a person has and the concept of what that person wants, needs or expects. In order to eliminate the dilemma in the field of health, we should facilitate the haemophiliacs' lives by serving the health care in a multidisciplinary view.

The Haemo-QoL Index: developing a short measure for health-related quality of life assessment in children and adolescents with haemophilia.

As quality of life (QoL) research is increasingly focusing on children and adolescents with haemophilia, the need for both age-appropriate and disease-specific assessment tools becomes apparent. Therefore, a set of questionnaires measuring QoL in children and adolescents with haemophilia was simultaneously developed in six languages within the European Haemo-QoL project (Haemophilia, 8, 2002, 47; Haemophilia, 10, 2004, 17). For implementation in larger studies and for use in daily clinical routine, a both short and psychometrically robust version of the questionnaire is needed. Using from the Haemo-QoL field study complete data sets of 306 children and adolescents (4-16 years) and their parents, a multivariate approach of item selection was applied to construct an eight-item instrument, the Haemo-QoL Index. The instrument is applicable to different age groups and represents the core content as well as the multidimensional structure of the original long versions. According to preliminary analyses, the index's psychometric performance concerning reliability and convergent validity is good. Further validation of the instrument's performance on a new and independent sample is needed.

Quality of life is associated to the orthopaedic status in haemophilic patients with inhibitors.

Inhibitors represent one major complication of haemophilia treatment, as they increase the risk of bleeding, physical disability and mortality. The Cost Of Care Inhibitors Study (COCIS) showed that modern strategies applied to manage patients with inhibitors adsorb high amounts of resources but provide satisfactory levels of Health-Related Quality-of-Life (HR-QoL). This paper focuses on determinants of HR-QoL in inhibitory patients. Fifty adult patients, enrolled by 11 Italian Haemophilia Centres, were clinically assessed and filled in two HR-QoL generic questionnaires: the EuroQol instrument (EQ-5D) and the Short Form-36 (SF-36). According to our results, bleeding frequency and inhibitor titres were not found associated with HR-QoL. Global HR-QoL, and in particular the physical component of wellbeing in these patients was found negatively associated with their orthopaedic condition: the EQ-5D Visual Analogue Scale (P<0.001) scores, the SF-36 domain 'physical functioning' and 'physical component summary' (P<0.01) scores were found significantly correlated with the orthopaedic joint score, even after adjusting for patients' age. These results were confirmed by those from the EQ-5D profile. To conclude, the COCIS study is the first study showing that HR-QoL in inhibitory patients is impaired by their orthopedic status, while other aspects do not seem to influence patients' global wellbeing. Our results suggest that while the management of this complication is satisfactory, the attention has now to be focused on the prevention of the orthopaedic problems in these patients, which nowadays constitute one of the most important aspects to be considered in the haemophilia care.

The use of a disability model in haemophilia research.

Most haemophilia research is medically orientated. However, assessment of the impact of disease on the individual is different when viewed from a rehabilitation perspective. Several models are available to explore functioning and health from this perspective. The disablement process (DP) is such a model, and the aim of this study was to introduce this process in haemophilia research to see whether this type of research could lead to meaningful data. Forty-three adult patients with severe haemophilia participated in this study in which the three 'main pathway' domains of the DP (impairments, functional limitations and disability) and two additional factors (intra-individual and risk factors) were addressed. Three questionnaires (HAL, Dutch-AIMS2 and IPA) were incorporated, and Pettersson scores for 21 patients were retrieved. Step-wise and hierarchical regression analysis was used to assess relationship between the various domains. Arthropathy explained 48% of the variance in functional limitations and nearly 25% of the variance in disability. Functional limitations explained 54% of the variance in disability. Patients identified pain as an important aspect of health which addressed 22% and 13% of the variance in functional limitations and disability respectively. Age was correlated with arthropathy (r = 0.85; P < 0.001), whereas psychological health correlated with pain (r = 0.67; P < 0.001). Both variables were also correlated with functional limitations and disability. Analyses adjusting for the effects of age and psychological health were subsequently performed resulting in more insight in the associations within the DP. The use of the DP in haemophilia research proved to be useful.

Experience of prophylaxis treatment in children with severe haemophilia.

The practice of prophylactic treatment of boys with severe haemophilia has been evaluated in our centre. Prophylaxis was started at the median age of 3.7 years (range 0.4-12.7 years) in 38/41 children (93%) under 17 years of age. Median follow-up was 4.1 years (range 0.4-12.7 years). The criteria of primary prophylaxis according to the definition by the European Paediatric Network of Haemophilia Management was fulfilled by 9/38 (24%). Although a majority [76%, 29/38] of the children started prophylaxis after a median number of joint bleeds of 3.5, 70% of the children in this group had clinical joint scores of 0. Intravenous catheter insertion was required at a median age of 15.5 months (range 5-36 months) in 21% of the children, resulting in a catheter infection rate of 1.74 per 1000 catheter days. None developed an inhibitor on prophylaxis and three patients who had low-titre inhibitors (< 5 Bethesda units) prior to prophylaxis had undetectable inhibitors after prophylaxis. The home-treatment training programme required considerable time and cost. As a result, 87% of the children used peripheral venous access and hospital visits declined as prophylaxis became established. Parents' incentives for prophylaxis were that the children undertook many physical activities and sports previously not recommended, there was less parental anxiety and an overall improvement in the quality of life for the whole family.

Health-related quality-of-life treatments for severe haemophilia: utility measurements using the Standard Gamble technique.

Prophylaxis for haemophilia improves outcomes, but at a substantial cost. Cost-utility analysis balances improvements seen in health-related quality of life (HRQoL) against costs, with the purpose of aiding healthcare decision-making. This analysis uses a measure of HRQoL known as utility. The objective of this study was to measure HRQoL (utility) values for states of health that result from on-demand therapy or prophylaxis. The HRQoL for different health states (including target joint bleeding, different intensities of prophylaxis, and indwelling intravenous catheters [ports]) was measured for healthy adults (n=30), parents of haemophilic children (n=30), and adults with haemophilia (n=28). Parents and patients rated health states similarly. Healthy adults gave the lowest ratings. The following rank, in order of HRQoL, was obtained: prophylaxis (low > medium > high) > on-demand therapy > prophylaxis with port> prophylaxis with infected port > on-demand therapy with development of a target joint. We conclude that: (1) haemophilia and its treatment reduce HRQoL; (2) prophylaxis is preferred to on-demand therapy; (3) intravenous ports substantially reduce HRQoL; (4) and an intravenous port to provide prophylaxis is preferable to on-demand therapy if a target joint develops.

Musculoskeletal pain and functional ability in haemophilia A and B. Physiotherapy and rehabilitation in haemophilia patients.

The present study was carried out to evaluate the progress of physical musculoskeletal ability and pain in Finnish haemophilia A and B patients during a given period of time and to find out the role of rehabilitation and physiotherapy in this process. In the physiotherapy/rehabilitation group, pain index by visual analogue scale (VAS) improved through time by 26%/4.6%. The nontreatment group showed slight aggravation. Regression analysis revealed that age, pain intensity, and functional disability in 1994 were the only significant explanatory factors influencing musculoskeletal functional ability at the end of the study. The current study was not planned as an intervention study and yet the results show some evidence, although not strongly, of the positive effect of physiotherapy and inpatient rehabilitation courses in reducing pain and functional disability for haemophilia patients. One of the important contributions of physiotherapy and rehabilitation is their educational role.