NIHRDataInsights/HRCSData huggingface dataset:
Title: An exploration of self-care in chronic low-back disorder from the perspectives of practitioners and patients: a Q methodological study
Funder: Department of Health (England)

Abstract: Background Chronic low back pain (CLBP) is a condition of medical and socio-economic importance. NHS policy encourages patients' active involvement in self-management as a key factor in improving quality of life in long term conditions. But, there is evidence that lack of appropriate support from health professionals is a barrier to supported self-management in low back pain. Clinical experience shows that treatment such as physiotherapy, for chronic low back pain can reduce symptoms and signs, but longer term the condition will often recur if patients do not engage in behavioural change in a self-managed way. Therefore systematic examination of stakeholders' perceptions of self-management is fundamental in optimising the quality and extent of healthcare provision for chronic low back pain. Aims •Identify the range and diversity of perceptions of patient partnership and supported self-management held by patients, health, social care and voluntary sector practitioners involved in management of patients with CLBP. •Gain insight into how practitioners can effectively facilitate patients to take an active part in their own care. •Utilise the emergent viewpoints to improve the quality of shared decision-making and self-management strategies in CLBP. •Use research findings to refine local CLBP management strategies. Plan of Investigation A research method called Q-methodology will be used. This examines how people think about a topic. Here it will used to understand and describe patients' and health professionals' subjective viewpoints on self-management. Participants will be recruited from an acute and 2 primary care NHS Trusts in the South of England to maximise breadth of cultural and demographic representation and facilitate inter-group comparisons. Stakeholder perceptions of self-management will be examined in the context of non-specific CLBP. The study findings will be presented at a consensus conference of stakeholders. Potential actions and practices will be proposed. These will be rated by delegates, with the intention of reaching consensus on the most important issues to inform subsequent recommendations. Potential Impact The socio-economic impact, chronic course, and uncertain causation, makes chronic low back pain an important issue. The findings of this research will be used to •enhance self-management of CLBP by increasing understanding of associated factors. •contribute to practitioner development and service user initiatives to improve long-term management of CLBP, through training events and related education packages. •influence and refine CLBP management strategies in participating Trusts in the short, medium and long-term •in the longer term successfully implemented self-management programmes may reduce recurrent episodes of CLBP.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: MUSCULOSKELETAL
Title: Primary care management of work-related issues in patients with back pain: screening and targeting patients at risk of work absence
Funder: Department of Health (England)

Abstract: Background: Back pain is a frequent cause of work absence.Objective: To design and assess the acceptability and feasibility of an intervention to manage work-related issues in primary care patients with back pain.Design: Literature reviews to contribute to the design of an intervention and a pilot study to test the intervention.Outcomes: (i) An intervention implemented in primary care to reduce the rate of work absence. (ii) Pilot data about acceptability and feasibility of the intervention to support the development of a definitive cluster randomised controlled trial.Benefits: Screening and targeting patients in primary care may enable the prevention and associated costs of work absence due to back pain. The intervention will identify and develop opportunities for extended roles of practice nurses in the management of common painful syndromes in primary care.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MUSCULOSKELETAL
Title: Prefabricated and custom orthoses in early RA (PREACHER)
Funder: Department of Health (England)

Abstract: Foot pain and deformity affect up to 90% of patients with RA and substantially impacts their quality of life. We aim to gain new insights into foot deformity and explore the potential of a range of insoles to prevent these irreversible changes from developing. A team of international experts will develop a new technique to examine foot deformity, compare a range of different insoles, and explore how we will test these in a large randomised controlled trial. This fellowship will provide vital new understanding of foot deformity and how it can be treated to improve patients’ quality of life.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS;6.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL
Title: Application of deuteratd water (2H2O) to define the etiology of musculoskeletal decline in ageing and the efficacy of nutritional supplementation
Funder: The Dunhill Medical Trust

Abstract: We have previously used amino-acid tracers in an acute laboratory setting to define, and test interventions for ameliorating age-related dysregulation of skeletal muscle protein metabolism. Nevertheless, this approach belies the facts that sarcopenia is the culmination of coordinated metabolic dysfunction in muscle, bone and tendon tissues (i.e. altered protein, lipid, and nucleic-acid metabolism) and also that acute metabolic readouts in a laboratory-setting may not reflect the chronic scenario of an uncontrolled, free-living older individual. Herein, we propose a new tracer-approach (2H2O) to quantify protein but also nucleic-acid and lipid metabolism over long-periods (weeks-months) in all musculoskeletal tissues (muscle, bone, tendon) in free-living aged humans. Moreover, we will test the long-term efficacy of nutriments (HMB and Omega-3 fatty acids) we have shown to be acutely anabolic. This approach will afford new insight into the aetiology of musculoskeletal ageing and identify the true anabolic efficacy of nutritional interventions in a chronic setting.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Towards the next generation of joint repair strategies. Using plasma polymerization to produce bioinspired, biofunctional, biomaterial implants
Funder: The Dunhill Medical Trust

Abstract: Osteoarthritis is a leading cause of functional disability in older adults worldwide. Current therapies cannot halt joint degeneration and prosthetic joints may be required to restore mobility. These have a finite working life, may not have the natural range of movement, and device loosening is problematic. Healthy cartilage contains stored biological factors (BFs), which maintain chondrocyte phenotype and tissue integrity. These BFs are sequestered by their tight non-covalent binding to matrix glycosaminoglycans.We propose fabricating bio-functionalised implants mimicking this cartilage-sequestering mechanism for regenerating traumatic and early osteoarthritic lesions in situ. For proof of principle, poly-L-lactic acid-based scaffolds will be plasma-polymerised with allyl amine to allow non-covalent attachment of the glycosaminoglycan, heparin to the scaffold. Chondrogenic and mesenchymal stem cell (MSC)-migratory molecules (i.e. transforming growth factor-β3 and chemokine CXCL-12) will be adsorbed to the glycosaminoglycan-scaffold. Implants will be tested for directed migration of MSCs, chondrogenic differentiation and cartilage matrix deposition


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL
Title: The role of long intergenic RNAs (LincRNAs) in mediating inflammation and joint pathology in osteoarthritis
Funder: The Dunhill Medical Trust

Abstract: Inflammation is increasingly recognized as key pathological driver in osteoarthritis (OA). We have previously reported on the role of small non-coding RNAs (microRNAs) in mediating inflammation in OA disease. However, the role of the recently identified long intergenic non-coding RNAs (lincRNAs) in OA is not known. Importantly, we recently identified lincRNAs that are rapidly expressed in response to inflammatory stimuli and can mediate the release of the pro-inflammatory cytokine IL-8 in human immune cells, suggesting that lincRNAs may be central regulators of inflammation. Given the role of inflammation in OA pathology, we hypothesise that lincRNAs mediate the pathophysiology of OA by regulating cellular inflammatory responses in the OA joint. This proposal will identify differentially expressed lincRNAs in human knee and hip OA cartilage and determine the functional role of these lincRNAs in OA pathology in order to identify new drug targets and new target combinations for therapeutic development.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Augmenting sirtuin activity to drive cartilage regeneration and treat osteoarthritis.
Funder: The Dunhill Medical Trust

Abstract: Osteoarthritis (OA) is a highly prevalent disease involving degeneration of articular cartilage and chronic inflammation of the joints. Age is the major risk factor for OA. Sirtuins (SIRT1-7) are NAD+-dependent enzymes which protect against many age-related pathologies and chronic inflammation. Studies indicate an essential role of SIRT1 for cartilage homeostasis and its deficiency is associated with osteoarthritic degeneration. However, the mechanisms which regulate sirtuin expression and activity in cartilage remain to be elucidated. We observed that glucose-restriction of cultured articular chondrocytes (i) stimulated the expression of SIRT1 and the mitochondrial SIRT3, (ii) induced a rapid metabolic switch from glycolysis to mitochondrial metabolism and (iii) augmented their ability to regenerate cartilage. The proposed study will test the hypothesis that glucose restriction augments the regenerative potential of articular chondrocytes in a sirtuin-mediated mechanism and that this requires a metabolic shift from glycolysis to mitochondrial metabolism.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL
Title: Novel nano-based antimicrobial and osteoconductive coatings for orthopaedic implants
Funder: The Dunhill Medical Trust

Abstract: There is an urgent need for new orthopaedic implant coating materials, which would be of particular benefit to the older patient. The use of nanoparticulate zinc oxide in this capacity has the potential to offer major advantages. Nano ZnO is recognised for its antimicrobial activity against key bacterial pathogens and its superior osteoconductive properties. A patented technique, namely, template assisted electrohydrodynamic deposition (PCT/GB2009/002788) has been developed by the applicants for preparing nanostructured coatings. The process offers attractive advantages of compatibility with micro-fabrication technology and versatility in pattern specification for advanced implant designs. The applicants have also developed a coated implant prototype with an optimised concentration of nano ZnO that is osteoconductive, antimicrobial and biocompatible. However, in order for this to be introduced within the orthopaedic health care sector further cellular, molecular and mechanical stability investigations to confirm the product’s benefits are needed and form the basis of this application


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL
Title: HipLink: Registry - Retreival linkage to help understand failure mechanisms of Metal on Metal hip relacement
Funder: The Dunhill Medical Trust

Abstract: Data on failure rate of hip implants from the UK National Joint Registry (NJR) was used to recall some types of metal on metal (MOM) hips in 2010, 2011 and 2012. An earlier recall would have prevented patient suffering but it is unclear when such action should be taken in the future for other implants. We aim to improve this process of post-marketing surveillance. We will link the NJR database to a database of 1400 failed hip implants collected by The London Implant Retrieval Centre (LIRC). This will enable us to assess the quality of the NJR data and for the linked records we will have a greater level of detail (such as the mechanism of failure form the LIRC) to explain the reason for their failure and to determine whether there should be ongoing, future linkage to enhance implant surveillance. Our findings will be generalizable to all medical implants.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MUSCULOSKELETAL
Title: MicroRNA in tendinopathy
Funder: Chief Scientist Office (Scotland)

Abstract: We have previously shown that microRNA family member expression is significantly altered in damaged human and murine tendons. We have demonstrated novel effector function for miR in the regulation of alarmin function in the early inflammatory response. This together with the emerging role of miR family members in the post transcriptional regulation of collagen synthesis prompts us to propose that miR may play a significant role in the integration of inflammatory and immediate tissue repair processes implicated in tendon healing. Therefore, the modulation of miR could represent a novel therapeutic approach to enhance tendon healing. Moreover miR could represent a pathway that defines a novel molecular link between tissue damage, matrix remodelling and inflammatory responses.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: The course of symptoms over time and the influence of the family on patterns of chronic pain.
Funder: Wellcome Trust

Abstract: Many common health problems, such as chronic pain and fatigue, do not have clear-cut causes that can be diagnosed and cured. For these problems it is important to know how and why they change over time. I have identified symptoms patterns in back pain consulters, and I will collect longer-term data to see whether these patterns are stable, or whether people get worse. I will consider why some people worsen and others do not by comparing their physical, psychological and social characteristics. I will apply these findings to patients with different symptoms to see if they are relevant. This could help health professionals choose specific treatments for patients who have had their symptoms for different times. Second, I will look at how patients families influence their health. I will collect data from back pain patients families to see whether people are more likely to have severe pain if their family has it. I will then compare GP consultations for different families to see whethe r people are more likely to go to their GP if their spouse or parents have also sought care. In the long-term, this may show that healthcare professionals should consider a patients family in their assessment.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: MUSCULOSKELETAL
Title: Defining disease models in mouse models of chondrodysplasia
Funder: Wellcome Trust

Abstract: The aim of this Fellowship is to determine the mechanisms of long bone growth and to characterise disease processes in human skeletal dysplasia. To determine the mechanistic link between the expression of a mutant gene and the resulting disruption to long-bone growth I generated mouse models of PSACH-MED resulting from mutations in COMP and matrilin-3. I have shown that reduced bone growth in these models results from decreased chondrocyte proliferation and increased/spatially dysregulated apopt osis. This change in cell phenotype is most likely due to cell stress induced by the expression of the mutant gene products. I will now use a multidisciplinary approach to determine 1) the contribution of UPR and cell stress to growth plate dysplasia and reduced bone growth, 2) if changes in the structure and function of the cartilage ECM contribute to the disease process and 3) the relative contributions of intracellular and extracellular disease mechanisms to the overall pathophysiology of cho ndrodysplasia. These studies will provide essential insight in the pathology of PSACH-MED and suggest potential therapies. They will also have a major impact on our understanding of disease mechanisms in other forms of chondrodysplasia and a broad spectrum of inherited connective tissue diseases.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: The role of AKT in mediating the adaptive response of osteoblasts to mechanical strain
Funder: Wellcome Trust

Abstract: This proposal outlines experiments to elucidate the pathways involved in bone cells early responses to mechanical strain. These are the first stages of the mechanically-adaptive process which ensures that bones are sufficiently strong to withstand normal functional loading without damage. We propose to establish in bone cell lines in vitro the relationship between the long recognised strain-related responses of bone cells involving the production of prostanoids, nitric oxide and IGFs and the mo re recently recognised involvement of beta-catenin and the Wnt pathway. We propose to investigate our hypothesis that AKT activity is regulated by strain and that AKT activity is a crucial regulator of transcription through beta-catenin and the Foxo family. We propose to establish whether the expression of SOST/sclerostin is influenced by AKT activity or regulated by strain independently. Finally we propose to establish the extent to which the presence of the estrogen receptor influences any or all of these strain-responses. Involvement of the ERalpha could not only explain our finding that in vivo the osteogenic response to loading is greatly diminished when ERalpha is blocked or absent but also the estrogen-related decline in bone mass in men and women associated with post-menopausal and age-related increase in fractures.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MUSCULOSKELETAL
Title: A Multidisciplinary investigation into the mechanics and biology of developing tendinopathy.
Funder: Wellcome Trust

Abstract: Tendons connect our muscles and bones, and are essential for movement. Constant use means they suffer fatigue damage, but this is normally repaired by the living tendon cells. However, if this goes wrong, damage can intensify, leading to an extremely painful and difficult to treat condition called tendinopathy. Tendinopathy is an important problem for both active and non-active individuals, accounting for 11 million UK work days lost annually. Despite decades of research, it is still unclear how tendinopathy develops, meaning we cannot improve the limited success of current treatments. This proposal uses a novel approach to examine how tendinopathy develops. Our research has led us to propose how overuse leads to cellular changes that spread throughout the tendon. We will investigate this using cow tendon that would otherwise be waste, and loading it in our specially designed fatigue generating apparatus, before examining it under a microscope to assess how damage affects tendon funct ion. We will also look at the cells during loading to see how they are affected, and use the latest biochemistry techniques to establish the cell response. By combining our engineering and biological expertise, we can provide the much needed evidence to improve treatment and help prevent tendinopathies.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Modification of skeletal muscle phenotype to treat neuromuscular diseases .
Funder: Wellcome Trust

Abstract: Duchenne muscular dystrophy is a fatal progressive muscle degenerative disease. There is a desperate need for therapies for this disease that affects young boys and men. The condition is the result of a genetic mutation that prevents expression of a protein that helps to stabilise the muscle cells. One approach to the development of therapies for this condition is to support the ability of the muscle to repair by increasing energy availability. We will test a gene therapy approach in the mouse m odel of this condition and based on those results we will test a variety of drugs, some of which are currently approved for use in other diseases. The hope is that one of these drugs will reduce the severity of the disease and can be rapidly taken to clinical trial and approval.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Investigating cartilage matrix turnover in health and disease using a quantitative proteomics approach.
Funder: Wellcome Trust

Abstract: Arthritis is a common disease that causes joint pain and results in failure of the joint cartilage. Cartilage functions as both a cushion and the Teflon-like friction-free surface that allows bones to move over each other. Cartilage is made up of building-blocks (aggrecan and collagen-II) whose physical properties contribute to how cartilage works. The body can chemically cleave these building-blocks using biological scissors known as enzymes. Both in health and disease there is turnover of th e cartilage building-blocks, which is in part controlled by enzymes. However in arthritis there is excessive cleaving of these building-blocks which is a major reason why cartilage fails. We aim to develop a novel method to measure the amount of both the damaging scissors and the effect of their damage. We will then identify how the normal turnover of building-blocks is distinct as cartilage ages in comparison to that seen in disease. We will also identify using a laboratory model of arthritis t he exact sequence in which cartilage building-blocks are cleaved and how different scissors effect this process. This will allow us to identify the earliest stages of arthritis helping us in the development of novel treatments as well as in techniques for early diagnosis.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: A Centre for Medical Engineering Solutions in the Management of Osteoarthritis.
Funder: Wellcome Trust

Abstract: Osteoarthritis is a common degenerative disorder affecting joints throughout the body, leading to significant pain and loss of mobility. Its central feature is a loss of properly functioning cartilage, the soft connective tissue that allows bones to slide easily over each other in the joints. We do not understand why cartilage loss occurs, although it is clear that there is a significant biomechanical (wear) component to the disease. The Centre will bring together engineers, biologists and clinicians to develop innovative and world leading technologies to better treat patients with osteoarthritis. We will develop sensor systems allowing earlier and more accurate diagnosis of osteoarthritis, and will make equipment allowing us to study the fundamental basis of this disease in a mouse model of osteoarthritis. We will determine the forces that act in the knee joint, and use this information to drive the development of new joint implants and orthotic systems We will develop equipment allowing more accurate and less invasive surgery on osteoarthritic joints, and will create the next generation of tissue engineered implants that use the body's own cells to replace damaged joint tissues. Finally, we will use novel sensor technology to improve the way that rehabilitation therapy is delivered to patients.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: MUSCULOSKELETAL