NIHRDataInsights/HRCSData huggingface dataset:
Title: Voice of customer market research for Renovite nanoclay product
Funder: Department of Health and Social Care

Abstract: Musculoskeletal conditions are the most common cause of chronic disability, affecting nearly a 3rd of the adult population, equating to 19 million adults, and 12,000 children in the UK1. Regional pain conditions, including low back and neck pain, commonly affect people of all ages2. Spine fusion procedures have and continue to increase in incidence (2.4-fold 2000-20093), with failure rates even at 20-40%4. Tissue grafts from the patient are currently considered the 'gold-standard' although they are severely limited, by donor site morbidity or quality. Alternatively, allogeneic bone or synthetic bone fillers can be used, but current solutions are not efficient in bone healing. Renovos, a young orthopaedic regenerative medicine company, spun out from the University of Southampton, and backed by Orthopaedic Research UK (a charity), is developing a novel biomaterial based on synthetic nanoclays, to accelerate bone healing and promote fusion, in a localised, safe, efficient and cost-effective manner (please see key publications5-10). Renovite&reg; is in pre-clinical development for promoting spinal fusion. This 4-month project will deliver &quot;voice of customer&quot; market research at a current critical stage of development, to narrow down on this device s most suitable first indication within spine orthopaedic surgery to lock in the design and take forward for clinical development (e.g. cervical vs lumbar interbody fusion procedure). 6 EU/UK and 6 US clinical key opinion leaders will be interviewed by a specialist external market research consultancy to provide feedback on the device under development and its use within a specific procedure based on needs and fit. Under this project, further interaction with clinicians during Eurospine in Milan and NASS in Chicago (key spine meetings) with further feed into addressing the evidence gap: an exact procedure to take forward with regulators and clinical development. Key materials for raising clinician, public/patient awareness of this technology will also be developed.


Research activity codes: 5.4 SURGERY;7.3 MANAGEMENT AND DECISION MAKING
Health categories: MUSCULOSKELETAL
Title: Feasibility of Recruiting an Early Scottish Knee osteoarthritis cOhort (FRESKO)
Funder: Chief Scientist Office, Scotland

Abstract: Osteoarthritis (OA) affects 800,000 people in Scotland. Current treatment options are limited to painkillers and, when pain becomes disabling, joint replacement. We will recruit people in Scotland with early knee OA (a common form of OA). Studying such people will allow us to better diagnose the disease in its early stages; identify what biological markers predict people whose disease will get worse quickly and why; and identify new (drug and non-drug) treatments. Our ultimate aim is to give each patient the specific treatment most likely to improve their disease.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Supporting people with musculoskeletal disorders in Scotland to remain in work: adapting the Making it Work™ intervention developed for people with inflammatory arthritis in Canada.
Funder: Chief Scientist Office, Scotland

Abstract: Musculoskeletal conditions affect around 1 in 3 Scottish adults and have a substantial impact on individuals’ work. There is a lack of services supporting individuals with long-term conditions, to help those who wish to remain working to do so. Making it Work™ is an online self-management programme developed in Canada which supports people working with inflammatory arthritis. The programme helped individuals to feel more capable to meet their work demands and reduced the likelihood of periods of sickness absence more than two months duration. Using group discussions and interviews, we will seek input from patients, employers, and healthcare professionals on aspects of the programme in order to expand it for people with a much wider range of musculoskeletal conditions in Scotland. Specifically we plan to expand the programme to individuals with non-inflammatory conditions such as osteoarthritis, fibromyalgia and chronic regional or widespread pain. We will work with experts and eLearning specialists to make changes to the programme based on this feedback and we will also establish how the programme could be delivered within NHS Scotland. After we have revised the programme, we will seek further patient feedback which will inform any final changes to the programme. The proposed research would lead to a modified version of an established programme and would inform a future study on the delivery of the programme within the NHS


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: MUSCULOSKELETAL
Title: Clinical Research Fellow – Developing a diagnostic app to predict non-union in long bone fractures.
Funder: Leeds Hospitals Charity

Abstract: Project aims 1. To evaluate whether previously identified risk factors to predict fracture non-union are accurate. 2. To assess the prototype app developed has a predicted value by being interrogated with new patient data. 3. Pending on the results of the above 2 aims, proceed with modification of the app already developed.

Lay abstract: 1. We have developed a scoring system to predict non-union in long bone fractures. 2. This scoring system has been developed into an app for easy use for clinicians (Leg Nui in the apple store). 3. 150 cases of tibial and femoral fractures will be assessed for further validation of the scoring system to predict non-union. 4. The results will allow us to improve the scoring system and the app if needed. 5. The results of this study will be published in a peer review journal. Project The task of the fellow would be to collect data related to the parameters used in the APP which can predict fracture non-union and compare the results between patients that united or developed non-union. The funds will cover the time of research 2 days a week for 12 months. The objective is to collect data, improve the APP and use these data to apply for grants. The fellow will not do a PhD after all. This study is being completed only by LTHT. The results of the research would help to verify the app and any changes required would be implemented 6-12 months after completion. If changes are needed for the app, funding would be required: I will be applying in august for a NIHR grant. This study could potentially lead to more grants. I will be applying in August and early next year when more data will be available. However, there is a 3-stage process and it will take at least 12 months to know. There should be no other additional costs. I think we can publish the results without utilising the open access option.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Adolescent centred outcome measures for Adolescent Ideopathic Scoliosis Surgery
Funder: Scoliosis Association UK

Abstract: Development of a person-centred core outcome set for adolescents and young adults with spinal deformity undergoing surgery: creation of a meaningful long list of candidate outcome domains (SPINE-COS-AYA)

Lay abstract: This study aims to engage with patients with spinal deformity, family members and healthcare professionals to generate a comprehensive and meaningful long list of candidate outcome domains for spinal surgery. A methodologically robust, capacity building approach will be taken in the development of an internationally applicable person-centred core outcome set.

Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL
Title: System for Kinematic Assessment of Painful Knees with Ultrasound Imaging
Funder: Versus Arthritis

Abstract: Development of a system and protocol for measuring in vivo patella tracking during knee flexion using ultrasound imaging in clinics. With a tracked ultrasound scan of the knee using wireless, handheld probes, the system will be able to reconstruct and measure the patella path during knee flexion. Patients will be able to view their scan in real-time to understand more about their joint’s function and why it hurts. With the opportunity to become actively involved in their assessment, it will encourage patients to discuss the treatment options available to them. This system has the potential to be used to routinely assess knee kinematics after joint replacement, particularly in those patients where it is suspected that pain is coming from the patellofemoral joint. This would be a brand new type of assessment where problematic joints can be imaged and assessed through their full range of motion. We have previously demonstrated the concept that underpins this proposal. The combination of ultrasound imaging and motion capture (MAUS – Motion Analysis & Ultrasound) was used to measure patella tracking while patients flexed their knees. In patients with a Total Knee Replacement (TKR) and normal subjects, MAUS showed significant differences in coronal plane patella tracking between the groups. With these differences in patellofemoral kinematics potentially related to outcome and the incidence of pain, this method showed promise for the assessment of patients post TKR. In the period since this study, we have continued to develop MAUS. We have: Accurately tracked the 3D position of the femur during treadmill walking Moved from a cart-based US system to handheld wireless probes Developed a method for automatically segmenting bone contours from US images Written software to access the image streams from two US probes while simultaneously applying the algorithm in 3 (above). Since the addition of automatic routines for bone segmentation and image registration, the system has been renamed CAT&MAUS (Computer-Aided Tracking with Motion Analysis & Ultrasound). The key aim of this proposal is to turn CAT&MAUS into a fast and reliable system for reconstructing the position of the patella relative to the femur at a series of knee flexion angles. The funding will be used to optimise and combine research methods that are currently distributed among various hardware and software into one easy-to-use system which can assess patients with painful knees. The next steps would include making the system compatible with analyses of other joints and adding artificial intelligence for scan interpretation and report generation.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: The Role of the Media in Influencing Perceptions of Osteoporosis and its Treatment
Funder: Versus Arthritis

Abstract: Background The media is a key social influence on understanding of health and illness. In the context of osteoporosis, the media have been blamed for the global decline in uptake of osteoporosis treatment; however, little is known about how osteoporosis is described in the media. This PhD aims to investigate the influence of media messages on perceptions of osteoporosis and make recommendations for production of media outputs and patient health information relating to osteoporosis and fracture prevention treatments. Methods The student will undertake 3 related studies: Phase 1. A media study to examine, using thematic and critical discourse analysis, how osteoporosis is defined and described in a range of traditional, digital and specialist media including newspapers, magazines, online news and television programmes. Phase 2. Six focus groups (2 with healthcare practitioners, 2 with people with osteoporosis, and 2 with people at risk of osteoporosis) to explore audience reception of media representations identified in Phase 1, and investigate how these become accepted in society and how they influence perceptions of treatment. Phase 3. Stakeholder workshops in partnership with Versus Arthritis and the Royal Osteoporosis Society, PPIE and other stakeholders to co-produce recommendations for health charities and other information providers in how to best frame their media outputs and patient information to counter common media-reported misconceptions. Impact and relevance to Versus Arthritis Versus Arthritis want to “provide the best information and support” to people with musculoskeletal conditions. Media messages can be a barrier to self-management and uptake of effective treatments (linking to Versus Arthritis priority areas in the pain roadmap for research). Understanding the way media constructs osteoporosis will be important in ensuring health charities and other information providers’ communication outputs are optimized and targeted appropriately, thus, promoting uptake of effective treatments, preventing fractures and ensuring patients maintain quality of life.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: MUSCULOSKELETAL
Title: Advanced spatial profiling of osteoarthritis development.
Funder: Versus Arthritis

Abstract: Molecular profiling can reveal the mechanisms controlling disease pathogenesis and holds huge potential for biomarker development, drug target discovery and disease phenotyping. Powerful technologies now enable deep interrogation of the molecular alterations (for example in mRNA and protein expression) that accompany disease onset and progression. Osteoarthritis research has made substantial progress using these strategies to document disease-associated molecular profiles. Almost invariably however, these analyses require the use of whole tissue or isolated cell homogenates, which lose critical positional information on the location of affected cells at the site of the pathological process. Existing profiling data is averaged across heterogeneous cell populations and cannot identify pathogenic tissue hotspots, the regulatory interplay between different cell types in situ and the coordination of disease progression. Only now is it technologically possible to address these issues. Our proposal will employ a time and cost-efficient two-stage deep tissue analysis strategy with high spatial resolution to identify the key molecular events associated with osteoarthritis onset in situ. Initially, mass spectrometry imaging will be used to screen regional changes in the molecular profile of the early osteoarthritic joint in tissue sections using timed samples from an osteoarthritis mouse model. Informed by this work, we will then conduct Digital Spatial Profiling (DSP). We have established the UK’s first DSP facility. DSP enables highly multiplexed quantification of up to 800 targets (mRNA and protein) across a single tissue section in multiple selected regions (commonly 30) simultaneously down to single cell resolution. We will build a molecular map of osteoarthritis onset. Through bioinformatic integration of our new and existing, publicly available profiling data we will select key disease-associated molecular candidates for analysis in human osteoarthritis samples and functional testing in vitro. Our ultimate aim is to identify new therapeutic targets, disease biomarkers and indicators for patient stratification.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Development of a novel Perceptual Training intervention (PeTra) to improve pain in people with fibromyalgia
Funder: Versus Arthritis

Abstract: People with fibromyalgia suffer from widespread pain, exhaustion and other physical symptoms. Fibromyalgia affects about 5% of people and can cause major disability and distress. There are several treatments for fibromyalgia already, including drugs, physical therapy and Cognitive Behaviour Therapy. However, up to 50% of people do not benefit very much from these treatments, or continue to have significant problems over time. Research and theory suggests that fibromyalgia results from a central sensitisation process, in which normally innocuous sensory inputs trigger an exaggerated brain response. Work from our group and others suggests that this arises when the brain struggles to judge the strength of signals coming from the body, causing it to misinterpret normal signals as dangerous. This suggests that it should be possible to reduce pain in people with fibromyalgia by reversing this deficit in perceptual discrimination. The purpose of the proposed PhD is to develop and begin to test a new treatment for fibromyalgia ("PeTra") that targets this deficit with an operant conditioning paradigm designed to train perceptual sensitivity. Our goals are to show that PeTra is safe, feasible to deliver and acceptable to people with fibromyalgia, and to obtain initial evidence that it has the expected effects on perceptual discrimination and pain in this group. We will begin by developing the PeTra paradigm and conduct experimental studies on healthy volunteers to optimise the training for clinical testing. We will then conduct a large experimental case series with 30 treatment-resistant fibromyalgia patients, using a multiple baselines design to test whether PeTra is safe, feasible and acceptable, and has a positive effect on pain and body perception. If successful, the proposed work will provide the platform for a future funding application for a clinical trial of PeTra.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MUSCULOSKELETAL
Title: Dissecting the role of YOD1 and ATXN3 deubiquitinases in fine-tuning the cellular responses to mechanical injury driving articular cartilage damage and osteoarthritis
Funder: Versus Arthritis

Abstract: Mechanical injury results in chronic inflammation and predisposes to tissue damage and loss of function. This is a feature of several musculoskeletal disorders, including osteoarthritis. There is a pressing need for disease-modifying therapies for osteoarthritis. Identifying the cellular mechanisms regulating injury cellular responses is crucial for understanding the disease mechanism and for designing new treatments. Recently, we have discovered that injury to articular cartilage rapidly activates the formation of Lysine-63 polyubiquitination in mammalian cartilage and in zebrafish connective tissues, and identified a unique ubiquitin signature for injury signalling. Ubiquitination is reversible and dynamically controlled by the opposing actions of ubiquitin ligases and deubiquitinating enzymes (DUBs). Our recent studies established that YOD1 and ATXN3 DUBs are differentially ubiquitinated and activated following articular cartilage injury as well as in human osteoarthritic cartilage. Furthermore, DUB inhibition significantly reduced neutrophil recruitment to injuries which implicates an involvement of DUBs in injury-induced inflammation. We propose that YOD1 and ATXN3 are critical regulators of chronic inflammation, underpinning tissue damage in osteoarthritis. In this studentship, the student will identify the role of YOD1 and ATXN3 enzymes in mediating injury cellular responses and tissue damage. We propose three specific objectives: 1) To modulate YOD1 and ATXN3 deubiquitinase activity in vivo using loss/gain-of-function models, 2) To determine the role of YOD1 and ATXN3 in tissue injury-induced inflammation and the skeletal system function and 3) To identify inhibitors for targeting YOD1 and ATXN3 DUBs in injury signalling using a customised chemical library. Transparent transgenic zebrafish lines are well suited for modelling and monitoring the dynamics of injury responses in vivo. Using cutting edge technologies including advanced transgenesis and high resolution live imaging techniques, the student will delineate the role of YOD1 and ATXN3 in regulating the injury-induced cellular responses and will determine their potential as promising therapeutic targets in osteoarthritis.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Targeting heparan 6-O-sulfation to promote repair of osteoarthritic cartilage.
Funder: Versus Arthritis

Abstract: To develop effective drugs for treating osteoarthritis, we need to understand the molecular mechanisms that coordinate and maintain joint health. Heparan sulfate (HS) proteoglycans orchestrate multiple protective pathways in cartilage, by regulating the retention and biological activity of many growth factors (e. g. FGFs, Wnts and TGFβ) and metalloproteinase inhibitors (e. g. tissue inhibitor of metalloproteinases 3, TIMP-3). We recently found that HS isolated from osteoarthritic cartilage has a different structure to that isolated from normal cartilage, with higher levels of O-sulfation at the 6 carbon position of N-acetylglucosamine. Such 6-O-sulfation is known to change HS interaction with many of its ligands, including growth factors that have substantial effects on cartilage homeostasis. This leads us to hypothesize that increased 6-O-sulfation will alter protective signaling pathways in cartilage, and accelerate progression of osteoarthritis. To investigate this hypothesis, we aim to characterize the 6-O-sulfate interactome in normal and osteoarthritic cartilage by mass spectrometry, and to investigate the impact of 6-O-sulfation on the biological activity of the identified ligands. This will define the molecular consequences of elevated 6-O-sulfation in cartilage, establishing a novel pathway of osteoarthritis pathogenesis. Such knowledge will enable us to design strategies for counteracting 6-O-sulfation and promoting repair of osteoarthritic cartilage. The project will additionally provide the selected student with excellent training for a career in musculoskeletal or allied biomedical research, as well as a broad range of transferable skills.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: A novel antibacterial titanium implant technology for total joint arthroplasty
Funder: Versus Arthritis

Abstract: Recent data emerging from the National Joint Registry indicates that our health care providers are performing approximately 180 thousand total joint replacements each year in England and Wales alone. Of these around 1-2% will fail because of infection. Infected implants have a significant socio-economic impact; revision arthroplasty is a huge burden for the patient and the cost of replacing infected knee and hip prostheses is estimated to cost over £50 million each year. With the prediction of a more elderly demographic over time the financial constraints on our NHS will merely escalate. Clearly there is an incentive to find ways of minimising infection risk of titanium (Ti) implants, and indeed other implantable materials, through the development of cost-effective antibacterial coatings that target, primarily, MRSA, the major miscreant for total joint infections. Our approach towards the facile development of an antibacterial Ti technology has been inspired from two very different scientific disciplines. The first is chromatography, specifically the development of teicoplanin (TP)-bound stationary supports for enantiomeric separations. The glycopeptide antibiotic TP, which kills MRSA, retains biological function when immobilised, a key property towards developing a new antibacterial coating. The second discipline is bioadhesion, as inspired by the edible blue mussel which has led to the development of polydopamine (PDA) thin films for (bio)material functionalisations. Using PDA as a secondary reaction platform we have successfully tethered TP to Ti to produce an antibacterial surface finish. Our exciting PhD scholarship pertains to the development and in vitro assessment of this technology as a potential solution towards reducing implant failures. The key goals (thesis chapters) towards the successful completion of the scholarship are: PDA-TP coating optimisation; microbiological and physiochemical assessment. Biocompatibility of the technology towards osteoblasts, stem cells and a simulated in vivo environment. Coating stability to sterilisation, long term storage and physical insult.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL