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.

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.

Using theory of change to co-create a programme theory for a telerehabilitation intervention for pain management in people with haemophilia.

BACKGROUND: Improved approaches for chronic pain management are a clinical and research priority for people with haemophilia (PWH). Involving people with lived experience in the design of a complex rehabilitation intervention strengthens the credibility and plausibility of the intervention, particularly in relation to rare disorders. Here we describe using a 'Theory of Change' (ToC) dialogue-based stakeholder process to create a programme theory for a telerehabilitation intervention. METHODS: An online workshop was convened and stakeholders received a briefing document in advance. Five stakeholders took part (3 PWH and 2 physiotherapists). At the workshop the group first agreed the overall aim of the intervention. Discussions then identified the resources, activities, barriers and enablers needed to achieve this outcome. All discussions were recorded and annotated by the workshop moderator. Behaviour change techniques were mapped for inclusion in the theory. RESULTS: A programme theory and narrative report were produced. All stakeholders reviewed these for clarity and to ensure a true reflection of the workshop discussions. Agreement was based on how meaningful, well-defined, do-able, plausible, credible, and testable each component was. Stakeholders highlighted the importance of issues unique to PWH. Key components included the need for physiotherapists to be knowledgeable of the condition, a range of exercises that were inclusive of all abilities, and the need for people to feel safe and supported whilst taking part. CONCLUSIONS: Co-developed theory based approaches to intervention design offer an inclusive and transparent way to develop novel and meaningful interventions for people with complex health conditions. The ToC is wholly transparent in its design and content. Together with the identified behaviour change techniques, the theory informs the protocol for a feasibility study evaluating a telerehabilitation intervention. Importantly, it allows the opportunity to revise, adapt and improve the programme theory for further implementation and evaluation.

Educational needs of patients, families, and healthcare professionals to support the patient journey in haemophilia gene therapy in the UK.

With the first gene therapies for haemophilia approved by the European Commission, the US Food and Drug Administration, and the Medicines and Healthcare products Regulatory Agency, it is important to consider the remaining unmet needs and challenges that may arise throughout patients' treatment journeys. We discuss existing unmet needs and important considerations prior to, during, and following haemophilia gene therapy treatment in the UK, and propose potential next steps. Key areas for attention are education, psychological support, and guidance on implementation. Strategies are urgently required to fulfil these needs. An immediate priority for information providers should be comprehensive education for people with haemophilia (PWH) and healthcare professionals (HCPs). Greater access to resources and training in psychological services will be required throughout the treatment pathway. More specific guidance is required to define the implementation model, criteria for accreditation, and responsibilities of care centres. Furthermore, PWH may revisit discussions with HCPs multiple times pre-infusion, thus the patient journey is unlikely to be linear. Consideration of these challenges, and of potential strategies to address them, will be integral to optimising the future success of this promising therapy.

Recommending swimming to people with low back pain: A scoping review.

BACKGROUND: It is common practice for health professionals to recommend swimming to people with low back pain (LBP) despite limited evidence. The aim of this review was to gain an understanding of the current evidence base supporting the recommendation of swimming to people with LBP. METHODS: A scoping review was conducted searching five electronic databases, CINAHL, MEDLINE, PEDro, PubMed, and SPORTdiscus using the keywords back pain AND swim*. The studies were grouped by study design and the following uncertainties were considered; the impact of swimming on the spine and LBP, evidence of swimming increasing or reducing the risk of LBP and the use of swimming in LBP rehabilitation programmes. RESULTS: 25 studies met the eligibility criteria; including sixteen observational studies exploring the relationship between swimming and LBP, three biomechanical studies investigating the impact of swimming on the spine, and five interventional studies of which four integrated swimming into a rehabilitation programme and one used swimming to modify lumbar lordosis. CONCLUSION: The review confirmed there is limited research and only low-level evidence to support the recommendation of swimming to people with LBP. Observational studies make up the greater proportion of research undertaken in the field; the data indicates that swimming is a low-risk form of exercise but not without risk. The findings from biomechanical research suggest that lumbar lordosis does not increase excessively when swimming breaststroke, but certain swimming techniques could negatively impact LBP and interventional trials illustrate that there are various ways to integrate swimming into a rehabilitation programme.

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.

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.

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.

Feasibility and Safety of a Powered Exoskeleton for Balance Training for People Living with Multiple Sclerosis: A Single-Group Preliminary Study (Rapper III).

OBJECTIVE: To evaluate the feasibility, usability, safety, and potential health benefits of using an exoskeleton device for rehabilitation of people living with multiple sclerosis. DESIGN: Single-group preliminary study. SUBJECTS: Eleven adults living with multiple sclerosis, with Expanded Disability Status Scores that ranged from 6 to 7.5 (mean age (standard deviation; SD) 54.2 (11.8) years), were recruited. METHODS: Individual participants undertook a balance rehabilitation exercise programme using the Rex Rehab robotic exoskeleton device. Each participant undertook 4 × 45-60 min supervised, balance exercise sessions. Primary outcomes were: (i) the number of participants who completed the trial protocol safely, and (ii) the number and nature of adverse events reported. Secondary outcomes were: mobility; balance; spasticity; sleep; functional independence; quality of life; and device satisfaction. RESULTS: Ten out of 11 participants completed the trial protocol safely. Four adverse events were recorded (1 serious), all of which were deemed unrelated to the trial. Secondary outcomes showed allied improvements in balance, joint mobility, spasticity and quality of life. All participants found the device acceptable to use. CONCLUSION: These results suggest that it is feasible and safe to use the Rex Rehab exoskeleton device to assist with balance rehabilitation for people living with multiple sclerosis.

Twelve-month prevalence of haemarthrosis and joint disease using the Haemophilia Joint Health score: evaluation of the UK National Haemophilia Database and Haemtrack patient reported data: an observational study.

OBJECTIVES: To report the 12-month prevalence of joint bleeds from the National Haemophilia Database (NHD) and Haemtrack, a patient-reported online treatment diary and concurrent joint disease status using the haemophilia joint health score (HJHS) at individual joint level, in children and adults with severe haemophilia A and B (HA/HB) without a current inhibitor. DESIGN: A 2018 retrospective database study of NHD from which 2238 cases were identified, 463 patients had fully itemised HJHS of whom 273 were compliant in recording treatment using Haemtrack. SETTING: England, Wales and Scotland, UK. PARTICIPANTS: Children (<18 years) and adults (≥18 years) with severe HA and HB (factor VIII/factor IX, <0.01 iu/mL) without a current inhibitor. PRIMARY AND SECONDARY OUTCOMES: Prevalence of joint haemarthrosis and concurrent joint health measured using the HJHS. RESULTS: The median (IQR) age of children was 10 (6-13) and adults 40 (29-50) years. Haemarthrosis prevalence in HA/HB children was 33% and 47%, respectively, and 60% and 42%, respectively, in adults. The most common site of haemarthrosis in children was the knee in HA and ankle in HB. In adults, the incidence of haemarthrosis at the ankles and elbows was equal. The median total HJHS in HA/HB children was 0 and in adults with HA/HB, were 18 and 11, respectively. In adults with HA/HB, the median ankle HJHS of 4.0 was higher than the median HJHS of 1.0 for both the knee and elbow. CONCLUSION: Despite therapeutic advances, only two-thirds of children and one-third of adults were bleed-free, even in a UK cohort selected for high compliance with prophylaxis. The median HJHS of zero in children suggests joint health is relatively unaffected during childhood. In adults, bleed rates were highest in ankles and elbows, but the ankles led to substantially worse joint health scores.

The Role of Physiotherapy in the New Treatment Landscape for Haemophilia.

The physiotherapist plays an essential role for people with haemophilia, an inherited bleeding disease responsible for musculoskeletal complications. Yet, with the advent of new and advanced therapies, the medical landscape is changing, and physiotherapy must adapt alongside. This paper considers whether there will still be a need for physiotherapy in the era of advanced therapies, and discusses ways in which services should evolve to complement emerging treatment paradigms for haemostasis in people with haemophilia. Ultimately, physiotherapy will remain an important element of care, even for people with little joint damage and low risks in the era of the new mild phenotype. However, competencies will need to evolve, and physiotherapists in both primary care and specialist treatment centres should work with haematology colleagues to develop more sensitive tools for detecting early joint changes. Physiotherapists will also play a crucial role in counselling and physically coaching, monitoring the musculoskeletal status of people with haemophilia who have transitioned to new treatments.

Haemophilia.

Haemophilia A and B are rare congenital, recessive X-linked disorders caused by lack or deficiency of clotting factor VIII (FVIII) or IX (FIX), respectively. The severity of the disease depends on the reduction of levels of FVIII or FIX, which are determined by the type of the causative mutation in the genes encoding the factors (F8 and F9, respectively). The hallmark clinical characteristic, especially in untreated severe forms, is bleeding (spontaneous or after trauma) into major joints such as ankles, knees and elbows, which can result in the development of arthropathy. Intracranial bleeds and bleeds into internal organs may be life-threatening. The median life expectancy was ~30 years until the 1960s, but improved understanding of the disorder and development of efficacious therapy based on prophylactic replacement of the missing factor has caused a paradigm shift, and today individuals with haemophilia can look forward to a virtually normal life expectancy and quality of life. Nevertheless, the potential development of inhibitory antibodies to infused factor is still a major hurdle to overcome in a substantial proportion of patients. Finally, gene therapy for both types of haemophilia has progressed remarkably and could soon become a reality.

Feasibility, safety and acceptability of select outcome measures in a physiotherapy study protocol for boys with haemophilia.

BACKGROUND: There is a lack of functional performance measures for children and young people with haemophilia (CYPwH) with associated control data from typically developing boys (TDB). The literature advocates development of a core set of outcome measures for different chronic conditions. As medical treatment improves, CYPwH are experiencing better outcomes; therefore, more challenging measures are required to monitor physical performance. Such testing is not performed routinely, due to practical and safety concerns. AIM: Evaluate the feasibility, safety and acceptability of select outcome measures as part of a study protocol testing CYPwH; including myometry, 10 metre incremental shuttle walk test (10-m ISWT), iSTEP (an incremental step test, with data from TDB), and 1 week of accelerometry-wear at home. METHODS: Sixty-six boys aged 6-15 years with mild, moderate or severe haemophilia A or B (including inhibitors) attending routine clinics at Great Ormond Street Hospital were approached to participate. Descriptive statistics and content analysis were used to assess outcomes of feasibility, safety and acceptability, which included recruitment/retention rates, protocol completion within routine appointment timeframes, performance testing without serious adverse events/reactions (SAE/SARs), and acceptability to CYPwH of high-level performance measures. RESULTS: Outcomes were met: 43 boys completed testing at clinic review (Jan-Nov 2018) within a 10-month timeframe, retention was 95% at completion of protocol and no SAE/SARs were reported throughout testing. CONCLUSION: Feasibility, safety and acceptability of the study protocol have been established in this population. Both high-level performance tests, iSTEP and 10-m ISWT, were an acceptable addition to boys' routine clinic appointments and could be safe, acceptable choices of outcome measure as part of a core set of tests for CYPwH. Further investigation of the psychometric properties for the iSTEP is now justified, in order for it to be used as a standardised, validated, reliable outcome measure in clinical or research settings. TRIAL REGISTRATION: Retrospectively registered on September 3, 2019, on ClinicalTrials.gov (ID: NCT04076306 ).

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.

The importance of cancer patients' functional recollections to explore the acceptability of an isometric-resistance exercise intervention: A qualitative study.

BACKGROUND AND AIMS: Although it has been widely recognized the potential of physical activity to help cancer patients' preparation for and recovery from surgery, there is little consideration of patient reflections and recovery experiences to help shape adherence to exercise programs. The aim was to explore the acceptability of our newly proposed isometric exercise program in a large general hospital trust in England providing specialist cancer care by using patient recollections of illness and therapy prior to undertaking a randomized controlled trial. METHODS: Four Focus groups (FGs) were conducted with cancer survivors with an explicit focus on patient identity, functional capacity, physical strength, exercise advice, types of activities as well as the timing of our exercise program and its suitability. Thematic framework analysis was used with NVivo 11. RESULTS: FG data was collected in January 2016. A total of 13 patients were participated, 10 were male and 3 were female with participants' ages ranging from 39 to 77. Data saturation was achieved when no new information had been generated reaching "information redundancy." Participants reflected upon their post-surgery recovery experiences on the appropriateness and suitability of the proposed intervention, what they thought about its delivery and format, and with hindsight what the psychological enablers and barriers would be to participation. CONCLUSION: Based upon the subjective recollections and recovery experiences of cancer survivors, isometric-resistance exercise interventions tailored to individuals with abdominal cancer has the potential to be acceptable for perioperative patients to help increase their physical activity and can also help with emotional and psychological recovery.