Using evidence-based co-design to develop a hybrid delivered exercise intervention that aims to increase confidence to exercise in people with haemophilia.

INTRODUCTION: Due to advances in treatments, people with haemophilia (PWH) are living longer. They are not as active as the general population due to joint damage and lack confidence to be active due to concerns about further bleeds and pain. There is a need to facilitate healthy aging through promotion of physical activity (PA) and exercise. Changing patient beliefs and increasing physical literacy and confidence to move are thought to be key to helping PWH become more active. AIM: This paper describes the development of an exercise and behaviour change intervention to improve confidence to exercise in PWH. METHODS: The 4-stage Medical Research Council framework for complex intervention development was used. RESULTS: Stakeholders included 17 PWH and 7 physiotherapists working in haemophilia. Seven online focus group meetings were held. The final intervention is a hybrid 12-week physiotherapist led progressive exercise programme. Classes are 45 min including Pilates, High intensity interval training and balance elements, together with discussion sessions focusing on PA recommendations, the types and benefits of different exercise styles and the effects of PA, together with the effects of aging for PWH. The COM-B model of behaviour change was used to develop the intervention. CONCLUSION: Co-design helps to produce an intervention that understands the stakeholders needs. Through this process the intervention developed to incorporate not only increasing PA but also confidence to exercise. The use of behaviour change theory identified the behaviour techniques included in the intervention and aims to increase physical literacy in this population.

A clinical practice guideline for primary care physiotherapy in patients with haemophilia.

INTRODUCTION: As a result of centralisation of haemophilia care to a limited number of intramural settings, many persons with haemophilia have to travel long distances to attend their haemophilia specialised treatment centre. However, regular physiotherapy treatment can be provided by primary care physiotherapists in the person's own region. Due to the rarity of the disease most primary care physiotherapists have limited experience with this population. This study aims to provide a clinical practice guideline for primary care physiotherapists working with persons with bleeding disorders. METHOD: A list of the most urgent key-questions was derived from a previous study. Literature was summarised using the grading of recommendations assessment, development, and evaluation (GRADE) evidence-to-decision framework. Recommendations were drafted based on four 90 min consensus meetings with expert physiotherapists. Recommendations were finalised after feedback and >80% consensus of all stakeholders (including PWH, physiotherapists, haematologists and the corresponding societies). RESULTS: A list of 82 recommendations was formulated to support primary care physiotherapists when treating a person with a bleeding disorder. These recommendations could be divided into 13 categories: two including recommendations on organisation of care, six on therapy for adult patients with bleeding disorders and five on therapy adaptations for paediatric care. Therapy recommendations included treatment after a joint- or muscle bleed, haemophilic arthropathy, chronic synovitis, non-haemophilia related conditions and orthopaedic surgery. CONCLUSION: An evidence-based practice guideline, based on current evidence from literature and clinical expertise, has been developed for primary care physiotherapists treating a person with haemophilia. To improve care, the recommendations should be implemented in daily practice.

Expert United Kingdom consensus on the preservation of joint health in people with moderate and severe haemophilia A: A modified Delphi panel.

AIM: For people with haemophilia A (PwHA), bleeding in the joints leads to joint damage and haemophilia-related arthropathy, impacting range of motion and life expectancy. Existing guidelines for managing haemophilia A support healthcare professionals (HCPs) and PwHA in their efforts to preserve joint health. However, such guidance should be reviewed, considering emerging evidence and consensus as presented in this manuscript. METHODS: Fifteen HCPs experienced in the management of PwHA in the UK participated in a three-round Delphi panel. Consensus was defined at ≥70% of panellists agreeing or disagreeing for Likert-scale questions, and ≥70% selecting the same option for multiple- or single-choice questions. Questions not reaching consensus were revised for the next round. RESULTS: 26.8% (11/41), 44.8% (13/29) and 93.3% (14/15) of statements reached consensus in Rounds 1, 2 and 3, respectively. HCPs agreed that prophylaxis should be offered to patients with a baseline factor VIII (FVIII) level of ≤5 IU/dL and that, where there is no treatment burden, the aim of prophylaxis should be to achieve a trough FVIII level ≥15 IU/dL and maintain a longer period with FVIII levels of ≥20-30 IU/dL to provide better bleed protection. The aspirational goal for PwHA is to prevent all joint bleeds, which may be achieved by maintaining normalised (50-150 IU/dL) FVIII levels. CONCLUSION: The panel of experts were largely aligned on approaches to preserving joint health in PwHA, and this consensus may help guide HCPs.

How to assess, detect, and manage joint involvement in the era of transformational therapies: Role of point-of-care ultrasound.

BACKGROUND: Patients with haemophilia experience recurring hemarthroses, mainly involving knees, elbows and ankles, which lead to haemophilic arthropathy, the major chronic complication of haemophilia. With new approaches to haemophilia treatment leading to fewer joint bleeds and, in some cases, no bleeding events, assessing whether current outcome assessment tools provide adequate sensitivity and specificity for management and care of patients with haemophilia is needed. METHODS: An overview of current imaging tools for monitoring joint health, novel osteochondral damage and synovial proliferation biomarkers, and the relationship between assessments for functionality and imaging modalities is provided. Usefulness and sensitivity of point-of-care ultrasound (POCUS) to complement other assessments and use of ultrasound to monitor haemophilic arthropathy are also examined. RESULTS: This review provides rationale for haemophilia teams to move beyond traditional outcomes in joint imaging, as well as guidance and evidence on assessment of joint health for potential new treatment modalities, such as gene therapy. The role of POCUS in the existing paradigm for haemophilia care and management along with the use of ultrasound as a complement to other outcome assessment tools are also discussed. Finally, the clinical effects of subclinical bleeding on joint function are described, to motivate screening for synovial proliferation. CONCLUSION: POCUS can facilitate the early detection of joint damage and can monitor disease progression while providing insights into the efficacy of treatment regimens, and should be considered as an essential assessment tool for managing the care of patients with haemophilia.

Accreditation model of European Haemophilia Centres in the era of novel treatments and gene therapy.

INTRODUCTION: The international certification of haemophilia centres in Europe is run by the European Association of Haemophilia and Allied Disorders (EAHAD) and European Haemophilia Consortium (EHC) since 2013. The centres are designated as European Haemophilia Comprehensive Care Centres (EHCCC) or European Haemophilia Treatment Centres (EHTC), based on the specific requirements which evaluate centres' ability to provide care for patients with haemophilia and allied disorders. AIM: To establish the new protocol for accreditation of European Haemophilia Centres. METHODS: EAHAD, in collaboration with EHC, established Accreditation Working Group with the aim to define necessary measures to safeguard quality and improvement of bleeding disorders care throughout Europe and to build a novel model for accreditation of European Haemophilia Centres. RESULTS: The European guidelines for certification of haemophilia centres have been updated to guidelines for the accreditation and include all the requirements regarding facilities, laboratory and personnel needed for optimal management of novel treatment options, including the introduction of the hub-and-spoke model for delivery of gene therapy. A pilot project for the accreditation of haemophilia centres including on-site audit has been designed. CONCLUSION: Implementation of the novel accreditation protocol of the haemophilia treatment and haemophilia gene therapy centres has been made to further improve the quality of care for patients with haemophilia and other inherited bleeding disorders.

Emicizumab prophylaxis in haemophilia A with inhibitors: Three years follow-up from the UK Haemophilia Centre Doctors' Organisation (UKHCDO).

INTRODUCTION: The UK National Haemophilia Database (NHD) collects data from all UK persons with haemophilia A with inhibitors (PwHA-I). It is well-placed to investigate patient selection, clinical outcomes, drug safety and other issues not addressed in clinical trials of emicizumab. AIMS: To determine safety, bleeding outcomes and early effects on joint health of emicizumab prophylaxis in a large, unselected cohort using national registry and patient reported Haemtrack (HT) data between 01 January 2018 and 30 September 2021. METHODS: Prospectively collected bleeding outcomes were analysed in people with ≥6 months emicizumab HT data and compared with previous treatment if available. Change in paired Haemophilia Joint Health Scores (HJHS) were analysed in a subgroup. Adverse events (AEs) reports were collected and adjudicated centrally. RESULTS: This analysis includes 117 PwHA-I. Mean annualised bleeding rate (ABR) was .32 (95% CI, .18; .39) over a median 42 months treatment with emicizumab. Within-person comparison (n = 74) demonstrated an 89% reduction in ABR after switching to emicizumab and an increase in zero treated bleed rate from 45 to 88% (p < .01). In a subgroup of 37 people, total HJHS improved in 36%, remained stable in 46% and deteriorated in 18%, with a median (IQR) within-person change of -2.0 (-9, 1.5) (p = .04). Three arterial thrombotic events were reported, two possibly drug related. Other AEs were generally non-severe and usually limited to early treatment, included cutaneous reactions (3.6%), headaches (1.4%), nausea (2.8%) and arthralgia (1.4%). CONCLUSIONS: Emicizumab prophylaxis is associated with sustained low bleeding rates and was generally well-tolerated in people with haemophilia A and inhibitors.

Identifying performance-based outcome measures of physical function in people with haemophilia (IPOP).

INTRODUCTION: Recent recommendations of core outcome sets for haemophilia highlight the need for including measures of performance-based physical health and physical function sustainability. To date, there is no consensus on what outcomes might be of value to clinicians and patients. AIM: To identify instruments of performance-based physical function to monitor musculoskeletal health in people with haemophilia that are practical in the clinical setting. METHODS: Utilising components from the Activities and Participation Category of the WHO International Classification of Functioning (WHO-ICF), a consensus-based, decision analysis approach was used to: identify activities people with haemophilia have most difficulty performing; identify quantitative performance-based measures of identified activities via a scoping review; and obtain views on acceptability of the tests utilising a DELPHI approach. RESULTS: Eleven activities were identified: maintaining a standing position, walking long distances, walking up and down stairs, walking on different surfaces, running, hopping, jumping, squatting, kneeling, undertaking a complex lower limb task, undertaking a complex upper limb task. Following a 2-round DELPHI survey of international physiotherapists, the 6-min walk test, timed up and down stairs, 30-s sit to stand, single leg stance, tandem stance, single hop for distance (children only) and timed up and go (adults only) reached consensus. CONCLUSION: This study is the first step in defining a core set of performance-based instruments to monitor physical health and sustainability of physical function outcomes in people with haemophilia. Establishing the psychometric properties of the instruments and whether they are meaningful to people with haemophilia is essential.

Physiotherapy interventions for pain management in haemophilia: A systematic review.

PURPOSE: Approximately 35%-50% of people with haemophilia (PWH) report living with chronic musculoskeletal pain. Although exercise based rehabilitation is effective for pain in other arthritises, there are no published guidelines for management of chronic pain in PWH. This review aims to evaluate and appraise the current evidence of effectiveness of physiotherapy interventions on (a) pain intensity, (b) quality of life (QoL) and (c) function in PWH. METHODS: A systematic review of five databases AMED and CINAHL, EMBASE and MEDLINE and PEDro, as well as trial registries, grey literature and hand searching key journals was completed. Included studies were critically appraised and evaluated for risk of bias. The GRADE approach was used to rate the quality of the evidence. RESULTS: Nine trials consisting of 235 participants met the inclusion criteria. All studies had an overall risk of bias with low methodological quality. Meta-analysis was not possible due to heterogeneity across trials. Studies comparing a range of physiotherapy interventions against no intervention showed no clear beneficial effect on pain intensity or QoL. Only one study, investigating hydrotherapy or land-based exercise against control, showed positive effect for pain intensity, but rated very low on GRADE assessment. Studies comparing one physiotherapy intervention against another showed no clear benefit on pain intensity, QoL or function. LASER with exercise and hydrotherapy were shown to have some positive effects on pain intensity, but no clear benefit on function. CONCLUSIONS: At present, there is limited evidence for the use of physiotherapy interventions in addressing the issue of pain in PWH. Better designed trials with higher quality and explicit methodology along with user involvement are needed to assess the efficacy of any proposed intervention.

Acceptability and Feasibility of an Isometric Resistance Exercise Program for Abdominal Cancer Surgery: An Embedded Qualitative Study.

Although it is recognized in the early stages of cancer recovery that changes in lifestyle including increases in physical activity improves physical function, there are no clear findings whether low versus moderate intensity activity or home or gym exercise offer optimal benefit. Isometric-resistance exercises can be carried out with very little equipment and space and can be performed while patients are bed-bound in hospital or at home. This embedded qualitative study, based in an English hospital trust providing specialist cancer care, was undertaken as a component of a feasibility trial to evaluate the acceptability and feasibility of an isometric-resistance exercise program and explore the suitability of functional assessments by drawing from the experiences of abdominal cancer patients following surgery. Telephone interviews were undertaken with 7 participants in the intervention group, and 8 interviews with the usual care group (n = 15). The gender composition consisted of 11 females and 4 males. Participants' ages ranged from 27 to 84 (M = 60.07, SD = 15.40). Interviews were conducted between August 2017 and May 2018, with audio files digitally recorded and data coded using thematic framework analysis. Our results show that blinding to intervention or usual care was a challenge, participants felt the intervention was safe and suitable aided by the assistance of a research nurse, yet, found the self-completion questionnaire tools hard to complete. Our study provides an insight of trial processes, participants' adherence and completion of exercise interventions, and informs the design and conduct of larger RCTs based on the experiences of abdominal cancer surgery patients.

Muscle strengthening intervention for boys with haemophilia: Developing and evaluating a best-practice exercise programme with boys, families and health-care professionals.

BACKGROUND: Muscle strengthening exercises have the potential to improve outcomes for boys with haemophilia, but it is unclear what types of exercise might be of benefit. We elicited the views of health-care professionals, boys and their families to create and assess a home-based muscle strengthening programme. OBJECTIVE: To design and develop a muscle strengthening programme with health-care professionals aimed at improving musculoskeletal health, and refine the intervention by engaging boys with haemophilia and their families (Study 1). Following delivery, qualitatively evaluate the feasibility and acceptability of the exercise programme with the boys and the study's physiotherapists (Study 2). DESIGN: A person-based approach was used for planning and designing the exercise programme, and evaluating it post-delivery. The following methods were utilized: modified nominal group technique (NGT) with health-care professionals; focus group with families; exit interviews with boys; and interviews with the study's physiotherapists. RESULTS: Themes identified to design and develop the intervention included exercises to lower limb and foot, dosage, age accommodating, location, supervision and monitoring and incentivization. Programme refinements were carried out following engagement with the boys and families who commented on: dosage, location, supervision and incentivization. Following delivery, the boys and physiotherapists commented on progression and adaptation, physiotherapist contact, goal-setting, creating routines and identifying suitable timeframes, and a repeated theme of incentivization. CONCLUSIONS: An exercise intervention was designed and refined through engagement with boys and their families. Boys and physiotherapists involved in the intervention's delivery were consulted who found the exercises to be generally acceptable with some minor refinements necessary.

Scope of practice of haemophilia physiotherapists: A European survey.

INTRODUCTION: European guidelines on the care of haemophilia recommend ready access to a range of services provided by a multidisciplinary team of specialists including physiotherapy. However, the scope of physiotherapy provided is unknown. METHODS: The Physiotherapists Committee of the European Association for Haemophilia and Allied Disorders (EAHAD) conducted a web-based survey to quantify the role and scope of practice of physiotherapists involved in haemophilia care. The survey was sent to more than 200 physiotherapists registered on the EAHAD database. Questions concerned their work practices including assessment and treatment activities and level of autonomy. RESULTS: Eighty physiotherapists from twenty-four European countries responded. Considerable heterogeneity exists in roles, responsibilities, and clinical practice of physiotherapists, particularly in access to and type of physiotherapy treatment provided, as well as the skill set and autonomy of physiotherapists to make independent assessment and treatment decisions. DISCUSSION: This pan-European survey establishes a context to support physiotherapy role development and professional identity. Key recommendations include the following: (a) establishing a pan-European network to support collaboration and education for physiotherapists working in haemophilia, (b) developing a core skills and capability framework to ensure person-centred approaches are central as well as working in partnership with those with the condition to maximize early recovery, support self-management and enablement in remaining active and independent, (c) regular training, standardized validation and maintenance of competency for assessment tools, (d) well-designed randomized clinical studies with larger numbers of participants from multiple sites should be the focus of future research.

Treatment regimens and outcomes in severe and moderate haemophilia A in the UK: The THUNDER study.

INTRODUCTION: The THUNDER study provides an analysis of treatment patterns and outcomes in UK patients with severe or moderate haemophilia A (SHA/MHA) in 2015. METHODS: Patients with SHA or MHA registered with the UK National Haemophilia Database (NHD) were segregated by severity, inhibitor status and age. Haemophilia joint health score (HJHS) was derived from NHD records and treatment regimen and annualized bleed/joint-bleed rate (ABR/AJBR) from Haemtrack (HT) in HT-compliant patients. RESULTS: We report 1810 patients with SHA and 864 with MHA. Prophylaxis was used in 94.9% (n = 130/137) of HT-compliant children <12 years with SHA, falling to 74.1% (n = 123/166) aged ≥40 years. Median ABR increased with age (1.0, IQR 0.0-5.0, <12 years; 3.0 IQR, 1.0-8.0, ≥40 years). Inhibitors were present in 159 (8.8%) SHA and 34 (3.9%) MHA. Median ABR increased from 2.0 (<12 years) to 21.0 (≥40 years) in SHA inhibitor patients using prophylaxis. Prophylaxis was used by 68.8% of HT-compliant MHA patients (n = 106) (median FVIII baseline 0.01 IU/mL) associated with a median (IQR) ABR of 3.0 (1.0-7.0). Median HJHS (n = 453) increased with age in SHA and MHA. Median (IQR) HJHS was higher in SHA inhibitor (17.0, 0.0-64.5) than non- or past inhibitor patients (7.0, 0.0-23.0). CONCLUSIONS: Increasing ABR with age persists despite current prophylaxis regimens. SHA and MHA had similar ABR/AJBR and HJHS, leading to a suspicion that a subgroup of MHA may be relatively undertreated. More intensive prophylaxis may improve outcomes, but this requires further study.

Outcomes of toric supplementary intraocular lenses for residual astigmatic refractive error in pseudophakic eyes.

PURPOSE: To evaluate rotational stability and visual and refractive outcomes of supplementary toric IOLs (Sulcoflex Toric 653T, Rayner Intraocular Lenses Ltd) for residual astigmatic refractive error in pseudophakic eyes. METHODS: A retrospective interventional case series was conducted in a single surgeon practice. Charts of patients who had Sulcoflex Toric supplementary IOLs inserted between June 2009 and September 2015 were reviewed. Outcomes were compared between eyes with and without prior corneal transplant. Patients with at least 3-months follow-up were included. RESULTS: In 51 eyes, mean UDVA improved from 20/86 to 20/43 (p = 0.002), though UDVA was better in eyes without corneal grafts (20/31) than eyes with (20/62). The proportion of eyes achieving 20/20 UDVA was 43%, 61% and 17% overall, in eyes with prior graft and in eyes with no prior graft, respectively. Sixty-four percentage achieved a spherical equivalent of within 0.5D of target (84% no graft, 34% prior graft). Fifty-three percentage of eyes achieved a cylinder of within 0.5D of target (no graft: 73%, prior graft: 0%). Mean lens rotation was 8.23° on day 1, and mean maximal rotation during follow-up was 17.63°. Sixty-two percentage of IOLs required repositioning. Of those that required repositioning, this was conducted a mean of 2.3 times. The mean final IOL rotation (following repositioning if required) was 6.17°. CONCLUSION: Sulcoflex Toric supplementary IOLs result in good visual and refractive outcomes in eyes with no prior corneal graft. However, outcomes are sub-optimal in eyes with prior corneal transplantation, and the majority of lenses require repositioning.