NIHRDataInsights/HRCSData huggingface dataset:
Title: THE JOINT ATLAS: A CELLULAR MAP OF KEY ANATOMICAL STRUCTURES IN THE HUMAN SYNOVIAL JOINT DURING DEVELOPMENT AND IN HEALTHY ADULTS.
Funder: Medical Research Council

Abstract: Understanding the genes that regulate the cellular interactions and secreted factors involved in cartilage, bone and limb development has provided important clues that have led to a more robust understanding of the functions of synovial joints and their associated structures in the adult joint. However, a systematic cellular atlas that describes the spatio-temporal organization of the cell subsets though which these genes work is missing. Using precision molecular analytics, multi-stage imaging and state of the art bioinformatics we will break down the artificial silos that have prevented the synovial joint from being explored as an integrated whole organ. Until now, almost all research into the biology and pathogenic processes that affect synovial joints has been performed in isolation, with different research teams focusing on their own specific cell types within the joint. Furthermore, teams have become divided into either medical or surgical specialties, into those that study inflammation or biomechanics and those that study cells or matrix. This has prevented a holistic approach to explore how the cellular components that make up the discrete anatomical structures in the joint relate to each other both from a developmental and a functional point of view. We intend to break down these research silos by developing a multidisciplinary consortium across three geographical sites in the UK (Oxford, Birmingham and Leeds) to construct a spatial-temporal cellular atlas of key synovial joint components during development and in healthy adults from four different joints. Such an atlas is essential in order to provide the underpinning knowledge to interpret the cellular changes that occur in response to inflammation, biomechanical injury and ageing


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Quality of life is a matter of distance? - A study investigating the relationship between centralising health services and health inequalities for patients with Rheumatoid Arthritis and Osteoarthritis.
Funder: Department of Health and Social Care

Abstract: The NHS is going through a process of changing where certain patients access healthcare services. This study will investigate the relationship between distance/ transport accessibility to healthcare services and health inequalities. It focuses on patients with Rheumatoid Arthritis and Osteoarthritis. The study includes: a systematic review, case study of Leeds Teaching Hospitals, analysis of secondary data using econometrics and scenario testing. Key outputs will provide the NHS with robust recommendations on the impact of distance/ transport accessibility to healthcare services on health inequalities and recommendations on minimising health inequalities from the policy.

Lay abstract: The NHS is going through a process of changing where certain patients access healthcare services. This study will investigate the relationship between distance/ transport accessibility to healthcare services and health inequalities. It focuses on patients with Rheumatoid Arthritis and Osteoarthritis. The study includes: a systematic review, case study of Leeds Teaching Hospitals, analysis of secondary data using econometrics and scenario testing. Key outputs will provide the NHS with robust recommendations on the impact of distance/ transport accessibility to healthcare services on health inequalities and recommendations on minimising health inequalities from the policy.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Active immunisation approach to combat chronic pain
Funder: Versus Arthritis

Abstract: Nerve growth factor (NGF) has been identified as a major mediator of chronic pain and a potential therapeutic target to provide relief from arthritic pain refractory to alternative treatments. The evaluation of anti-NGF antibody drugs are well advanced, validating the concept and revealing clues as to potential clinical applications for arthritis.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Evaluation of specialised splinting software to support design for 3D Printed wrist splints
Funder: Versus Arthritis

Abstract: This proposal seeks to develop a dedicated 3D Computer Aided Design (CAD) software for hand therapists so that they can benefit from the strengths of 3D Printing to improve functionality, fit and aesthetics of wearable medical devices (specifically wrist splints) for their patients.


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Identification of cytokines that drive progression of fibrosis in Dupuytren’s disease: therapeutic opportunities with biologics
Funder: Versus Arthritis

Abstract: Dupuytren’s contracture is a common fibrosis of the palmar fascia of the hand, which is a flattened tendon-like tissue. The formation of a scar-like tissue under the skin can prevent the tendons from extending properly, resulting in curled digits on the hand and concurrent disability. Surgical treatment is the gold standard for advanced disease however post-surgical complications and recurrence are common. The fibrotic tissue in Dupuytren’s consists of a ‘nodule’ region, which is thought to represent an active stage in the tissue pathogenesis and a ‘cord’ region comprising a residual scar-like tissue. Fibrotic tissue comprises cells and an abundant extracellular matrix. The formation of fibrotic tissue in Dupuytren’s is thought to result from an over-production of normal and abnormal extracellular collagens and cellular contractility causing extracellular matrix compaction.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Predicting disease development and optimising initial treatment for people living with psoriatic arthritis: a network cohort study.
Funder: Versus Arthritis

Abstract: Psoriatic arthritis (PsA), a complex heterogenous inflammatory arthritis, can significantly impact the quality of life and functional ability of the people living with it. The project outlined in this fellowship was developed from the results of the NIHR James Lind Priority Setting Partnership that investigated unmet needs in psoriasis and currently in progress in PsA that people living with the condition have identified as priorities for research. Our aim is to characterise the journey to diagnosis and to treatment in people living with PsA. Our objectives include: 1. Characterise the incidence of PsA and predict who will develop PsA from psoriasis. 2. Identify the clusters of co-morbidities that exist in both people with newly diagnosed psoriasis and PsA, prior to starting treatment. 3. Characterize drug utilization of people with PsA and how this is impacted by the co-morbidity clusters, as identified in 2. 4. Assess the comparative safety of first line treatments of PsA and links to other co-morbidities to identify adverse drug reactions of special interest. This will be achieved through a population-based retrospective multi-national cohort study, that has been designed and developed with patient research partners from the British PsA Consortium patient communication group. Data from routinely collected primary healthcare data from five international databases including CPRD GOLD (UK), CPRD AURUM (UK), SIDIAP (Spain), IPCI (Netherlands), and UK Biobank will be used. Known risk factors for the predictors for progression from psoriasis to PsA will be identified from a systematic literature review, and logistic regression and machine learning will be used to identify novel predictors. The variables that we will include in the co-morbidity clusters include associated conditions such as inflammatory bowel disease and the co-morbidities of interest including metabolic syndrome. The drug treatments of will include non-steroidal anti-inflammatory drugs, glucocorticoids and conventional synthetic disease modifying anti-rheumatic drugs.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Understanding personal shielding stories: The voice of people living with arthritis and musculoskeletal disease
Funder: Versus Arthritis

Abstract: People living with arthritis and MSK disease were amongst those identified as “clinically extremely vulnerable” to COVID-19 by NHS England. Research commissioned by Versus Arthritis found the approach to shielding was unclear, causing confusion and uncertainty. The CfEVA is text-mining outpatient letters to inform the shielding notification process. This study aims to complement the text-mining work, exploring shielding experiences. We aim to: Capture views and lived experience of the shielding process Understand what people with arthritis think of the need to shield, and its benefits and risks Use the findings to make recommendations regarding how the shielding process could be improved Use the findings to bring data from the text mining project to life This qualitative research will collect and analyse multiple forms of data from semi-structured interviews, focus groups, and materials which participants will be invited to contribute (videos, drawings, poems, creative writing). Up to 30 participants will be purposively sampled from Salford, which is diverse, using ours and CfEVA PPI group’s existing networks. We aim to include BAME communities (including English as second language); ‘official’ and ‘unofficial’ shielders; young adults; and people with different types of arthritis and MSK conditions. Data will be analysed thematically.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Long-term intraarticular delivery of glucocorticoids from novel particles
Funder: Versus Arthritis

Abstract: Glucocorticoids (GCs) are potent anti-inflammatory and analgesic treatments in musculoskeletal diseases and when delivered intraarticularly in arthritic joints they are amongst the most effective treatments. However, GCs are rapidly released from current depot formulations which are crystalline suspensions or polymer complexes so the beneficial effects do not persist much beyond a few weeks/months. We have manufactured a new formulation where GC crystals are incorporated into microchamber film arrays (MFA) produced by a soft lithography method. Preliminary data shows that release of the GC dexamethasone from MFA is very slow with the majority of the drug retained after 8 or 12 weeks in release experiments. Whilst we have previously prepared MFA with other cargo molecules their rate of release has been more rapid. We have also recently developed methods to convert MFA into individual microcapsules. In the studies in this proposal we will explore the influence of microchamber structure, shape, size and polymer wall thickness on GC release rate. We will then convert GC MFA into individual separated microcapsules to form a suspension of them and monitor and compare GC release rate with other formulations currently used in the clinic. Preclinical data will also be obtained in this study from experiments in mice where GC microcapsules delivered into stifle joints will be assessed for biocompatibility, retention and GC release into joints and blood through the use of a sensitive cell assay we have developed. The proportion of the released and remaining GC in the joint will be assessed at intervals up to 6 months after delivery. At the end of the proposed work we anticipate that we should be close to assessment in clinical trials. Although GCs are an established treatment in localised arthritis we anticipate that their prolonged delivery from the microcapsules proposed will represent a step change in this treatment modality making their use more convenient and cost effective. In terms of Versus Arthritis an improved local treatment for arthritic disease is in line with their aim to support the development of breakthrough treatments for musculoskeletal diseases.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: UK MSK TRC Collaboration Programme Manager
Funder: Versus Arthritis

Abstract: The charity is engaged with the Department of Health and Social Care (DHSC) in a joint initiative with National Institute for Health Research (NIHR) Office for Clinical Research Infrastructure (NOCRI) to strengthen coordination, engagement and investment across the UK musculoskeletal (MSK) experimental medicine landscape. This activity forms part of the Transformation Programme to grow UK MSK research through leverage. A two-phase approach to build a UK MSK Translational Research Collaboration (UK MSK TRC) is being progressed. The aim is to bind and align investment in MSK translational research, elevate it to a at a new level of ambition and focus UK-wide and so drive cutting edge translational research to improve outcomes for patients. Phase one will establish a refreshed and renewed Collaboration, to transition and align the existing NIHR Joint and inflammatory disease TRC and Versus Arthritis Experimental Treatment Centres to a UK MSK TRC that joins up the NIHR Biomedical Research Centres (BRC) and Clinical Research Facilities with MSK expertise. Phase two will scope approaches to sustaining and growing the UK MSK TRC in the longer term, with development of the business model to support further collaborative activities potentially including the establishment of a multi-functional research programme office structure around the UK MSK TRC. The first step is to fund in partnership with DHSC a Collaboration Programme Manager (CPM), the role has been developed by the two organisations and plans for Q4 2018 recruitment are underway. The role duration will initially match that of the current NIHR BRC investment to 31st March 2022, total costs of up to £300,000 are to be shared between Versus Arthritis and DHSC, at a level up to £150,000 each. As the employer of the current TRC Lead, Professor Pitzalis, funds will be awarded to Queen Mary University of London, the role will be hosted at the NOCRI Office (Twickenham).


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Identification and validation of novel T cell therapeutic targets in Ankylosing Spondylitis.
Funder: Versus Arthritis

Abstract: Background: Ankylosing Spondylitis (AS) is a common form of inflammatory arthritis without a cure. Genetic association studies have revealed 113 loci affecting the risk of developing AS, most of which lack functional explanations hindering their translation to patient benefits. More than half of the genes affecting the risk of developing AS are involved in T cells functions, suggesting the important role of T cells in the pathogenesis of AS. Through integration of GWAS, eQTL and transcriptome data, combined with functional validation of gene candidates regulating T cells in AS, this proposal focuses on identification of novel T cell therapeutic targets in AS. Methods: Gene candidates regulating T cell functions in AS will be identified through the integrated analysis of AS-associated genetic variations, CD4/CD8 eQTL, transcriptome of known AS-associated T cell subsets, transcriptome of CD4/CD8 from AS patients and healthy controls and single cell RNA-seq (scRNA-seq) of T cells from blood, joint synovial fluid/tissue from AS patients. Prioritized gene candidates will be firstly validated by gene knockdown in primary T cells from AS patients and healthy controls. The validated genes will then undergo second validation through CRISPR-knockout or gene overexpression. For 1-2 validated genes, in-depth mechanistic studies in relevant T cell subtypes will be performed. Key pathways related to validated genes will be identified through RNA-seq experiments of gene-silenced or knockout primary cells and scRNA-seq data mentioned above. Key proteins in the pathways will then be determined and validated through gene knockdown or knockout and relevant cellular assays. Potential applications: Proposed study will be the first to systematically investigate disease-associated genetic variants for the genes regulating T cell functions in AS. Data generated will provide functional explanations for AS-associated genetic loci, promote the understanding the AS pathogenesis, and potentially identify novel therapeutic targets for treatment of AS and other related arthritis.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Advanced Pain Discovery Platform Awards (APDP)
Funder: Versus Arthritis

Abstract: The APDP aims to deliver a consortium- based platform of national scale, generating discovery and early translational science that will break through the complexity of pain and reveal new treatment approaches to address a wide spectrum of chronic and debilitating clinical conditions. The APDP will provide new knowledge about the significant variation and unpredictability that exists in the lived experience of pain and uncover shared mechanisms, breaking down inconsistencies in diagnosis and treatment, providing new pain biomarkers and identify and validate new therapeutic interventions. The APDP is being delivered through four interlinked funding streams/activities: 1. Large, multidisciplinary, UK-wide consortia focused on data generation and consolidation in chronic pain. These will link together researchers across biomedical, social and data sciences. These consortia will gather together many different types of human clinical data related to pain including biological samples, imaging data and cognitive and psychosocial factor identification. This will be achieved through working with existing biological samples/clinical data and putting in place procedures to collect new samples. 2. Online open data platform for pain to provide a key resource for the national and international pain communities 3. Research grant funding – Mapping pain complexity and uncovering the molecular and cellular basis of pain 4. Research grant funding – Bioinformatics, Artificial Intelligence and machine learning Activities 3 and 4 represent funding for hypothesis driven research projects to build on the work of the consortia and will be rolled into a single funding call for research projects. ked activities: The funding will support the establishment of multi-disciplinary themed consortia to link together


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Lockdown walking in older adults with chronic MSK Pain: A mixed methods study
Funder: Versus Arthritis

Abstract: Physical activity (PA) improves pain and quality of life and reduces risk of further chronic illness in those with musculoskeletal pain. While increasing PA levels is a public health priority, the mechanisms to achieve this in older adults with chronic musculoskeletal pain remain unclear. Walking is the most likely way all adults can achieve recommended levels of physical activity. However, there is a lack of research into the effectiveness of interventions to promote walking for older people with musculoskeletal pain. Arthritis Research UK funded a study (20608) aimed at increasing PA in older people with chronic pain (iPOPP). Phase one comprised development work that defined the iPOPP intervention as two consultations with a health care assistant, provision of pedometer, pain toolkit, diary and 8 weekly motivational prompts. Phase two was the iPOPP pilot randomised controlled trial (RCT) to assess the acceptability and credibility of iPOPP, and to test the feasibility of trial processes. After satisfying the pilot trial success criteria, and amending aspects of the intervention and trial processes, our goal now is to test the effectiveness and cost effectiveness of iPOPP in a main trial. The objective of the iPOPP main trial is to investigate whether a brief behavioural intervention increases the amount of walking at 6 months in adults aged 65 years and over with chronic pain. Objective measures of physical activity (using accelerometers) will be collected prior to randomisation and at 6-month follow-up. Secondary objectives are to investigate pain, time spent sitting, self-efficacy to exercise, quality of life and health care use. We aim to randomise 1085 participants in a pragmatic, three-parallel-arm, assessor-blinded RCT comparing usual primary care plus the iPOPP walking intervention, with usual care with a pedometer and with usual primary care alone. The trial includes a full health economic evaluation and process evaluation.


Research activity codes: 6.7 PHYSICAL
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Title: Centre for Epidemiology Versus Arthritis
Funder: Versus Arthritis

Abstract: The Arthritis Research UK Centre for Epidemiology will address clinically important questions in musculoskeletal (MSK) disease that require a robust epidemiological approach, delivering results to make everyday life better for people living with arthritis. Key goals for the Centre are to: Enhance our understanding of the occurrence and progression of disease, and the effectiveness and safety of treatment. This will address the question “what does the future hold for me?”, will inform patients and other stakeholders on how to influence the occurrence, progression or impact of disease, and will usefully guide treatment decisions for clinicians and patients. Deliver methodological excellence, including harnessing digital data in the emerging era of digital epidemiology, extending statistical design and analytics to make best use of modern data sources and computational methods, and ensuring the translation of research into practice through implementation science Build strategic partnerships that strengthen our key goals Enhance patient and public involvement and engagement to ensure that our research aligns with our users’ priorities, and that our findings reach the right audiences clearly and efficiently Deliver local, national and international teaching and learning, including coordination of the UK Research in Musculoskeletal Epidemiology (UK-RIME) network


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL