NIHRDataInsights/HRCSData huggingface dataset:
Title: UK heel fracture trial (UK HeFT)
Funder: Arthritis Research UK

Abstract: Fractures of the calcaneus or heel bone, are an important cause of hind foot osteoarthritis and consequent pain, loss of function, inability to work, economic loss and necessity for sub-talar fusion. Modern surgical techniques offer the opportunity to significantly reduce these risks after calcaneal fracture. These techniques are becoming widespread, but do have risks. They have not yet been proven and there is an urgent need to assess the clinical effectiveness of surgery for calcaneal fractures. This study is a pragmatic randomised controlled trial to estimate the effect of open reduction and internal fixation compared with non-operative treatment of displaced intra-articular fractures of the calcaneus fractures. 150 participants will be randomised during 18 months. The participants will followed-up with interim outcomes measured at 6,12 and 18 months. The principle outcome will be measured at two years after injury using validated subjective and objective measures.


Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Cortical thickness mapping of the proximal femur in hip fracture prediction
Funder: Arthritis Research UK

Abstract: This proposal targets osteoporotic hip fractures, one of the major ageing-related challenges faced worldwide, with annual total direct costs estimated at £21 billion. Our long-term goal is to improve health and quality of later life by understanding and preventing hip fragility fractures. Older adults sustain fracture when the load concentrated on a specific area of the femur (generated by a fall, trip or even a minor stumble) exceeds its strength. Current imaging methods that estimate bone mineral density (BMD) are specific for hip fracture risk but have low sensitivity, and cannot identify regional bone defects where fractures initiate. Cortical bone loss with ageing is increasingly seen as the key modifiable target for lifelong exercise and therapeutic interventions. We recently invented a way of mapping cortical thickness in any part of the skeleton in life using computed tomography. It has allowed us to identify areas of focal osteoporosis in hip fracture patients that cannot be identified by BMD tests. Therefore, this analysis plan proposal focuses on mapping regional cortical thinning across the life-course, and testing how well cortical thickness measurement predicts incident fracture in a large prospective study (with or without BMD) thereby paving the way towards defining programs of intervention.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Investigating the mechanism of the protective role of glutamate receptor antagonists against early onset osteoarthritis following joint destabilisation injuries.
Funder: Arthritis Research UK

Abstract: Osteoarthritis (OA) affects 8.5 million people in the UK; however, no cure exists and joint replacement is often the only option. Surgery is costly, carries risks, and up to 20% of patients find knee replacements dissatisfactory. We found that glutamate receptor (GluR) antagonists reduce pain, inflammation and joint degradation in inflammatory arthritis. Glutamatergic signalling associates with mechanical loading of bone and glutamate concentrations increase in OA and rheumatoid arthritis patients and animal models. We hypothesise that anterior cruciate ligament (ACL) or meniscal injury increases synovial fluid glutamate concentrations, activating GluRs that regulate bone remodelling, mechano-responses, inflammation and degeneration, and such GluRs may be therapeutically targeted after injury to protect against OA. We will determine (i) whether glutamate concentrations increase in joint fluids from ACL/meniscal injury patients, (ii) whether pathophysiological mechanical loading of bone explants/cells increases glutamate release, (iii) whether pathophysiological glutamate concentrations affect inflammatory, degradative and mechano-responses of bone, (iv) which GluRs mediate these responses in vitro and whether GluR antagonists alleviate OA following knee joint destabilisation in vivo. Effective antagonists will be ideal candidates for treatment and/or prevention of early onset OA following ACL/meniscus injury, and could improve the quality of life for this often young group of patients.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Accelerated rehabilitation for patients with a rupture of the Achilles tendon: A mixed methods approach to evaluating clinical and cost effectiveness.
Funder: Department of Health (England)

Abstract: Every year thousands of people tear the tendon that attaches their calf muscles to their heel bone (Achilles tendon). Following this injury we don’t know what the best treatment is, so research is needed. To find the best treatment, health professionals and academics will need to collaborate across the UK, which costs a lot of time and money. To make sure we get the answers without making costly mistakes, high quality pilot research is essential. This current research will develop and test pilot processes to inform the future larger study that will answer how best to treat this injury.


Research activity codes: 6.3 MEDICAL DEVICES;6.7 PHYSICAL
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis
Funder: Versus Arthritis

Abstract: We will build a world-leading research Centre by bringing together complimentary expertise in basic science, epidemiology, imaging, early osteoarthritis (OA), sport science, musculoskeletal medicine, surgery and allied health to further the understanding of the relationship between exercise, sport, injury and OA. The Centre will deliver in collaboration with patients, athletes and partners from key sporting organizations, industry our international collaborators and other ARUK, MRC and NIHR Centres. This will be achieved through the study of both our extensive established cohorts of the general population and athletes (covering the full spectrum of exercisers) and new bespoke injury and intermediate phenotype cohorts. This information will inform clinical risk modelling and improve understanding of the mechanisms of joint damage and the biomarkers of post-injury changes in joint and muscle function in both acute injury and high volume training scenarios. This will lead to novel and clinically testable strategies for prevention, assessment and treatment of injury, aimed at mitigating the risk of subsequent symptomatic OA. The Centre will support a programme of education and training in a unique environment. Throughout the research, a strategy of public, patient and sport involvement will be implemented in order to maximise effective dissemination of results and translatable benefit.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Arthritis Research UK Centre for Osteoarthritis Pathogenesis
Funder: Versus Arthritis

Abstract: The Kennedy Institute of Rheumatology (KIR) moving to the University of Oxford, to within 200m of the Botnar Institute and the Nuffield Orthopaedic Centre (NOC) will possibly create the highest concentration of OA researchers, with the broadest range of OA expertise within Europe.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Production and evaluation of a clinical tool to screen older women with back pain for vertebral fractures (Vfrac)
Funder: Versus Arthritis

Abstract: Women with osteoporotic vertebral fractures are important to identify, as they have one of the highest risks of further fracture with potentially devastating consequences and medication can reduce this risk by 30-70%. This project will refine a screening tool for primary care so that women at risk can receive appropriate and timely management.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.3 MANAGEMENT AND DECISION MAKING;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Arthritis Research UK Centre for OA Pathogenesis
Funder: Versus Arthritis

Abstract: The move of the Kennedy Institute to Oxford in 2013, catapulted the new Centre into an outstanding musculoskeletal environment with adjacency to the Botnar Research Centre, Target Discovery Institute and Wellcome Trust Genome Centre. We have had a highly productive first term of the Centre; integrating OA research across NDORMS, adding capacity through the creation of new career development fellowships, creating an internationally recognised Centre for OA research and training and identifying a number of important pathways/molecules in disease pathogenesis.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Upstream Strength Training Interventions to Improve the Ageing Trajectory of Women in Midlife
Funder: Economic and Social Research Council

Abstract: The healthy ageing narrative often focusses on later life (65 years+). This project centres on the assumption that healthy, productive ageing is a lifelong endeavour, and that the system must support upstream, proactive, health-generating interventions. The target population for this project is women in midlife. The overarching aim is to make it easier for women in midlife to engage in regular strength training by co-producing relevant, accessible solutions. This will enable is women in midlife to arrive at the 'start line' of older age with greater physical reserves and better musculoskeletal health. Objectives include 1) To engage a diverse range of women in midlife, 2) to complete 6-8 creative co-design workshops, 3) to generate and rapidly test multiple potential solutions that are desirable, feasible and viable 4) to identify one solution to take forward 5) to create a development plan for growing the solution.

Lay abstract: Falls in later life are a major threat to healthy ageing. They can lead to pain, injury, and loss of independence. Falls have a significant impact on health services, both immediate hospital care and long-term aftercare. The 60+ age group is growing faster than any other age group, therefore problems related to falls will increase. Women express fear of falling more than men and they sustain more hip fractures from falls. Current approaches focus on older people who have had a fall or are at risk of falling. More proactive approaches are needed earlier in life. Muscle strength is an essential 'building block' for healthy ageing. Strength declines as we age but it can be maintained through exercise. Approximately half of all women aged 45 years and over, do no regular strength exercises. The aim of this project is to find ways to make it easier for women in midlife to do regular muscle strength training. This would enable them to arrive at the 'start line' of later life in better health and with greater physical reserves. We will work closely with women in midlife to understand their thoughts and opinions about strength training. We want to understand what makes it harder for them to engage in strength training and what might make it easier. We will co-create a range of potential ideas and solutions, these will be tested out with other women and with key partners including healthcare professionals, academics, designers, fitness professionals and people who influence policy.

Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Recruitment of endogenous stem cells by targeted up-regulation of early inflammation to promote healing of fragility fractures
Funder: Medical Research Council

Abstract: Stem cells underpin healing and repair in all tissues. They may be harnessed to promote repair by culture and ex vivo activation before re-introduction, although this approach poses problems of cost and scalability as well as safety if the cells are virally transduced to overexpress growth factors. Our proposal aims to address the urgent unmet need to accelerate the healing of fragility fractures and improve implant adherence in osteoporotic bone by recruiting endogenous stem cells from a variety of local sources and inducing their osteogenic differentiation. This strategy also overcomes the time delay in expanding cells in vitro that precludes the treatment of fragility fractures, eg of the femoral neck, that should be treated surgically within 36hrs of injury for optimal clinical outcomes Our published data demonstrate that targeted up-regulation of inflammation by local administration of TNF at the fracture site accelerates healing and our preliminary data shows that this also pertains to osteoporotic fractures. We will validate these findings for fractures in mice rendered osteoporotic by oophorectomy as well as in Cushingoid animals. Surgical fixation of osteoporotic fractures often fails due to cut-out or pull-through of implants. We will also assess the effect of TNF administration on transosseous screw adherence. We currently administer TNF in PBS by local injection; however, this dissipates rapidly. In collaboration with Halozyme Therapeutics, we will develop the technology to precisely administer TNF using a FDA-approved carrier that is in a liquid phase at low temperatures and therefore suitable for injection. However it forms a gel at body temperature and hence will localize TNF to the fracture site for maximal efficacy. The preparations will be evaluated using our existing animal models that emulate the clinical problems encountered by reconstructive surgeons. Development and validation of this methodology will allow us to proceed to clinical trials


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Novel tendon attachment and repair strategy
Funder: Medical Research Council

Abstract: Tendons are susceptible to injury and their repair remains an unmet clinical need as only 60% achieve a satisfactory functional result. The UK incidence of flexor tendon injuries is >3,000 patients per annum, many of whom have multiple tendon injuries. Currently, there are inadequate surgical procedures for injured tendon; repair involves the formation of scar tissue which is biochemically and biomechanically inferior to natural tendon tissue. Tendon injuries can be severely disabling, with significant rehabilitation time and high healthcare costs. Our approach represents a paradigm shift with a novel device delivered by keyhole surgery. It also enables the transfer of load across different parts of the device as the tendon heals so that physiotherapy starts earlier and scar tissue formation is reduced. Our current DPFS project has characterised novel PCL electrospun scaffolds and generated compelling in-vivo data in short and long term small animal studies. The PCL fibres have demonstrated tendon repair in the rat model and through clinician-led design/FEA modelling techniques we have identified a novel concept for a medical device. We seek continued MRC support, to develop and demonstrate performance in larger animal studies and readiness for clinical evaluation. The team has the necessary expertise in biology, engineering and clinical practice and with MRC support the device will be developed for clinical readiness and commercialisation. A critical pathway to partnering the technology with an industrial partner for future clinical development has been defined through direct engagement, and will be achieved by the commercial, regulatory and design expertise included in the project team. A key aim of the project is to work with end users of the device to gain their feedback and guidance on the requirements of the product which drive both the commercialisation and clinical pathway for the research and development ultimately leading to improved patient outcomes.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: Evaluating health care improvements for patients with a hip fracture
Funder: Department of Health (England)

Abstract: Hip fracture is the commonest serious injury of older people. A major UK clinical audit has prompted various care improvements, and created a 250,000-case database that can be used to assess their effectiveness. However, changes to hospital care have been incremental, and their impact is difficult to measure. I propose to adapt techniques for analysing complex data structures used in other contexts to assess relationships between service changes, individual patient care and outcomes. This research will contribute robust evidence on what works in improving hip fracture care, together with techniques that might be applied more widely in the NHS.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: MUSCULOSKELETAL;INJURIES AND ACCIDENTS
Title: University of Newcastle Centre for Brain Ageing & Vitality supported by BBSRC, EPSRC, ESRC and MRC
Funder: Medical Research Council

Abstract: The MRC Centre for Brain Ageing and Vitality will develop innovative, world-class research and training related to brain ageing and frailty. The MRC Centre will be a partnership with Newcastle University and will be based in new purpose built laboratory space. The strategic added value from the MRC Centre for Brain Ageing and Vitality will come from targeted expansion of the interface between basic biogerontology and clinical brain ageing and by developing new programmes to address the relationship between the healthy ageing brain and the healthy ageing body. By focusing on vitality we will emphasise the considerable potential to deliver major benefits to patients and the general public, as well as reductions in the health and social care costs of an ageing population. The programme on brain ageing will address the following questions: what are the mechanisms of neuronal loss and dysfunction associated with age, how do these mechanisms vary between different neuronal populations and what role do mitochondria play in these processes; what are the links between mechanisms of intrinsic ageing and neurodegeneration/vascular disease, and how is this relationship affected by age-related changes in the neurovascular environment; what is the mechanism and importance of ageing of glial and stem cells? The programme on brain ageing will make use of the extensive (i) Newcastle Brain Tissue Resource (snap frozen and fixed tissue from 1000+ mostly older individuals) and (ii) a dedicated aged mouse unit. The programme on lifelong health and vitality will address the following research questions: what are the mechanisms involved in the protective effect of different forms of exercise on musculoskeletal ageing in terms of physiology, mitochondrial function and muscle/joint pathology; what is the impact of nutritional factors on musculoskeletal and brain ageing with particular emphasis on epigenetic and genetic modifications of nuclear and mitochondrial genomes? To achieve this we will build capacity in exercise physiology, magnetic resonance spectroscopy, in vitro biochemical and molecular methods and nutrition. The MRC Centre?s training programme will include integrated MRes/PhD for 12 students, development of an E-learning MRes, innovative workshops and public lectures. We will work closely with stakeholders and will build elements of research into the process of public engagement into our activities.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: MUSCULOSKELETAL;MENTAL HEALTH
Title: A novel targeted treatment for reducing anxiety in joint hypermobility: a proof of concept study
Funder: Versus Arthritis

Abstract: Brain and body are intrinsically linked. Joint hypermobility, a common variant of connective tissue, affects 20% of the population. It is associated with musculoskeletal disorder and dysautonomia (typically postural tachycardia). It is linked to increased likelihood of experiencing anxiety/panic (OR 4.39/6.72). Although anxiety and hypermobility are highly prevalent and this association has been recognised for some years, to date notargeted treatments exist. The proposed research builds on previous work of the applicant, demonstrating that mismatch between subjective and objective measures of changes in bodily sensations provoked by orthostasis predicts anxiety level in this population and this signal explains the relationship between activity in anterior insula and anxiety level. The goals of this project are three-fold. First, with experts, the applicant aims to develop and refine a novel non-pharmacological therapy which seeks to reduce this error by increasing correspondence between measured changes in heart rate and subjective judgement of these changes, using a combination of physiological (interoceptive) training and psychological training. Second, the applicant will conduct arandomised controlled ‘proof of concept’ trial to demonstrate the efficacy of the ntervention. Third, using data neuroimaging and psychophysiological data before and after treatment, the applicant will determine predictors of treatment success, in order to optimise future therapeutic interventions.This project will be transformative for patients by increasing awareness of the psychophysiological mechanisms of anxiety in hypermobility and its alleviation and also transformative for the applicants career: consolidating her expertise at the interface of musculoskeletal and psychiatric disorder.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MUSCULOSKELETAL;MENTAL HEALTH
Title: Integrated studies of working later in life: individual and contextual determinants of extended working
Funder: Medical Research Council

Abstract: With the growth of the older population predicted to continue in coming decades, it is important to understand how to encourage work participation among older people in jobs that will be satisfying and will promote healthy ageing. This research consortium will explore characteristics of individuals and their family, workplace and living environments that promote working beyond age 50. Using longitudinal studies from the UK, Finland, France and Sweden, the research questions are: * Do cumulative good (in addition to recent) working conditions promote extending working lives? * What impact do modifiable lifetime health behaviours have on working lives? * Do family factors including partnership and fertility histories relate to extended working lives and are they mediated or moderated by workplace predictors? * What are the individual workplace factors that enable people to remain in work if they have a chronic health condition? Or if they are caring for ill family or grandchildren? * Are there differences in how workplace, family factors and chronic health conditions influence extending working lives by gender, socioeconomic background, birth cohort or country? * Are there local area characteristics, for example related to the local labour market structure, that promote extended working lives and does their impact differ for workers with low skills or poor health?


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MUSCULOSKELETAL;MENTAL HEALTH;GENERIC HEALTH RELEVANCE