NIHRDataInsights/HRCSData huggingface dataset:
Title: Fully automated system for the analysis of the efficacy of knee replacement surgery
Funder: Medical Research Council

Abstract: This project aims to develop a computer-aided system to analyse radiographic signs of early joint failure in knee replacement surgery (KRS). The software system to be developed will be based on the BoneFinderTM-technology (www.bone-finder.com) which uses machine-learning methods to automatically locate skeletal structures in radiographs. Based on a set of training data consisting of radiographs and feature point annotations, BoneFinderTM uses Random Forest-based shape model matching methods to locate the corresponding feature points in unseen images. BoneFinderTM has been applied to automatically outline knee joints in radiographs but further methodological development is required to account for disease and to incorporate implant detection. For a given image, the automatically identified feature points will be used to quantify the knee bones and implant fitting. This will include conventional geometric measurements of lengths and angles but these only give a sparse representation of the structures. Statistical Shape and Appearance Models will be used to capture and quantify their overall shape and texture. Using retrospective data, machine-learning methods will be applied to combine the derived radiographic shape and appearance information of the knee joint with collected clinical data to analyse signs of early joint failure. This will lead to a computer-aided system that will have learned to identify radiographic indications of early joint failure based on radiographs and clinical data for any new subject, informing the KRS decision-making process. A feasibility study will be conducted to identify the clinical requirements for usability and acceptability, and for the integration of the system into the clinical workflow. This will also include the identification of a suitable implementation strategy of the system into the existing digital healthcare infrastructure. The system will be validated during a pilot trial.


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
Health categories: MUSCULOSKELETAL
Title: Collagen Calcium Phosphate Composite Devices for Bone Augmentation
Funder: Medical Research Scotland

Abstract: Above a certain (critical) size bone defects are difficult to treat, leading to failure of fractures to heal and failiure of the patients to return to full activity. Bone defect filling materials need to be bioactive to encourage bone healing, degradable as bone is one of only two body tissues that can repair with itself and finally have appropriate mechanical properties. Too stiff materials will remove loading from the bone and thus slow healing, while insufficient strength will lead to premature failure of the reparing tissue and thus lead to failure of the repair process. Collagen reinforced with bone mineral composites, by modelling the components and structure of bone, can provide the required biological and mechancial properties. This project will develop composite devices using collagen supplied by the industrial partner and will reinforce this with calcium phosphates, thus modelling the collagen reinforced with bone mineral structure of bone. The applications of the material will be as porous scaffolds to fill three dimensional defects and as sheets of material able to bridge defects or to provide space for bone healing. The material will be produced, optimised and tested from mechanical properties through to bone cell culture to ensure biocompatibility and bone bioactivity.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL
Title: Predicting the impact of exon skipping on dystrophin function
Funder: Muscular Dystrophy UK

Abstract: Two promising genetic treatment approaches for DMD (gene therapy and exon skipping) involve expression of internally-deleted dystrophins. While current clinical trials primarily seek to prolong ambulation, the ultimate goal is to also target respiratory and cardiac muscles to protect DMD patients from cardio-respiratory failure. Studies from our lab and others indicate that some internally-deleted dystrophins may not be as functional in cardiac and respiratory muscles as in limb muscles. Therefore, this application is concerned with understanding why some internally-deleted dystrophins are not optimally functional in respiratory and cardiac muscles in vivo. This knowledge is fundamental to select DMD patients that would most benefit from exon skipping treatment and identify exons worth targeting. Our hypothesis is that some deletions disrupt the structure of the central rod domain of dystrophin resulting in disruption of key protein interactions in the heart and diaphragm but not limb muscles. To test this hypothesis we propose a novel use of exon skipping technology to rapidly generate mouse models for two such internally-deleted dystrophins. We will then use a proteomics-based approach developed in my lab to characterize the interactome of internally-deleted dystrophins in cardiac, diaphragm and limb muscles in vivo relative to wild-type. This research will generate new knowledge that is fundamental to enable the rational design of exon skipping strategies and gene therapy constructs to offer improved protection from cardio-respiratory failure. Furthermore, it may identify dystrophin domains critical for function in different muscles.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: A natural history study of a cohort of adults with Duchenne Muscular Dystrophy living in the UK
Funder: Muscular Dystrophy UK

Abstract: Improvement in the standards of care and better treatment has substantially increased the life expectancy of boys with Duchenne muscular dystrophy (DMD) with the mean life expectancy of DMD improving from 19.5 years to late 20s and beyond. Data from the North Star database demonstrated significant benefit of corticosteroid treatment in the largest cohort studied at the time with mean age at loss of ambulation with daily steroids being 14 years and 12 years for intermittent steroids, compared with 9 years in historical controls. Understanding the natural history of rare disorders such as DMD is essential for choosing the best outcome measure for clinical trials. A benefit of the paediatric North star network was to standardise and improve the care of children with DMD reducing geographical variation. A study by CareNMD showed that DMD adults in the UK were dissatisfied with their medical care, compared with Paediatric services, and had poor participation compared with Denmark where most people with DMD were living independently. Furthermore, here is little published data on the natural history of adults with DMD to determine best outcome measures for clinical trials. This PhD project will drive the development of an adult North star network, it will develop and validate a dataset that will include both medical and psychosocial measures and aims to standardise clinical care. In addition, in a smaller cohort attending two centres, it will investigate changes in new parameters over time: Renal function, retinal function and bowel transit time together with quality of life.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MUSCULOSKELETAL
Title: Assessing muscle fibrosis by magnetic resonance imaging
Funder: Muscular Dystrophy UK

Abstract: Duchenne muscular dystrophy (DMD) is a life-limiting inherited condition. Advances in treatment of DMD have increased the importance of outcome measures. Clinical trials utilise functional assessments, potentially biased by motivation and comorbidities. Magnetic resonance imaging (MRI) is an objective and non-invasive measure which correlates with functional assessments. EP3533, a gadolinium-based contrast agent, has affinity to collagen 1. EP3533 has identified fibrosis within the heart, liver and lungs. Following our preliminary work in older mice, this project uses EP3533 to quantify fibrosis within skeletal and heart muscle in young mdx mice. The project will evaluate whether EP3533 can quantify levels of fibrosis following administration of an anti-fibrotic (halofuginone). The project involves administration of SGd and EP3533 one week apart, using young mdx mice and controls. T1 mapping and T1 weighted images will be obtained prior to administration then continuously afterwards. After the second scan, the heart and lower limb muscles will be harvested for the ex vivo quantification of fibrosis. The project will assess EP3533 in quantification of fibrosis over a 12 week course of halofuginone. Forty, 24 week old mdx mice will be divided: 20 receiving Halofuginone and controls. Treated mice receive halofuginone (3μg/g) three times per week. MRI takes place at baseline and week 13, focussing on lower limb muscles, they are then harvested for ex-vivo quantification of fibrosis. If effective, non-invasive measurement of fibrosis is possible, EP3533 will reduce sacrifice of valuable animals in longitudinal studies. Ultimately EP3533 could be used in clinical trials as an outcome measure.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Development costs for myotubular and centronulcear myopathies registry
Funder: Muscular Dystrophy UK

Abstract: The Myotubular and Centronuclear Myopathy Patient Registry (also referred to as the ‘MTM and CNM Registry’) is an international database specific to these conditions. It is managed from the UK and operated by TREAT-NMD at Newcastle University, in partnership with the Myotubular Trust. The registry has been developed in partnership with a number of leading neuromuscular researchers, and is jointly funded by the Myotubular Trust and Muscular Dystrophy UK.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: MUSCULOSKELETAL
Title: The function of the KY protein in early onset neuromuscular disease
Funder: Muscular Dystrophy UK

Abstract: The pivotal role of the KY gene in muscle function was first established in the mouse in 2001, but the importance of the so-called KYphoscoliosis peptidase (KY) in skeletal muscle physiology has recently been emphasised by the identification of novel human myopathies associated with KY deficiency. Neither the pathogenic mechanism of KY deficiency nor a specific role for KY in muscle function have been established. We have recently characterized that absence of KY undermines chaperon assisted selective autophagy (CASA) in mouse, fish and cell models of KY deficiency. Here, we propose that CASA disruption may play a role in the pathogenic mechanism of the human condition. Therefore, we will characterize CASA in samples from patients from a large pedigree from Israel, which segregates a loss of function mutation in the ky gene. In addition, the KY protein contains a predicted conserved transglutaminase/protease (TGN/PROT) domain and localizes to the Z-disc; however, enzymatic tests using purified KY and radiolabelled substrates have failed to show evidence of either of these enzymatic activities. Conversely, it has been speculated that the enigmatic TGN/PROT domain may serve protein protein interactions. Here, we have designed two approaches, modelling the 3D structure of KY and in vivo complementation studies in mice, to help us discriminate the enzymatic from the interactive role. The cumulative evidence provided by these results will pave the way for a more accurate functional annotation of the KY protein, providing insights into the pathogenic mechanism triggered by KY deficiency.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Nusinersen for treating infant or child spinal muscular atrophy [ID1069]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of nusinersen within its marketing authorisation for treating spinal muscular atrophy.

Lay abstract: Spinal muscular atrophy, or SMA, is a rare genetic disorder that causes muscle weakness and progressive loss of movement. It is most commonly caused by defects in the gene SMN1, which leads to degeneration of motor neurones in the spinal cord (this is termed ‘5q SMA’). The motor neurones most affected by this condition are those that allow walking, crawling, arm movement, head and neck movement, swallowing and breathing. SMA causes substantial disability, and may lead to increased mortality and reduced life expectancy. The most severe forms of SMA typically cause death before age 2 years, although people with later-onset types of SMA usually live into adolescence or adulthood. SMA also has substantial effects on families and carers, including the impact of caring for the patient, the need for specialist equipment and ongoing emotional, financial and social impacts. SMA is a heterogeneous condition, which is often grouped into 4 main types, based on the age of onset of symptoms and how much motor function the person has. The types of SMA decrease in severity from type 1, in which symptoms arise before age 6 months, to type 4 (adult-onset). Babies with SMA type 1 have low muscle tone (hypotonia) and severe muscle weakness which affects movement, swallowing and breathing. In type 2 SMA, the onset of symptoms is between 7 and 18 months of age, and people with this condition are often severely disabled and unable to walk unaided. Type 3 SMA is a heterogeneous condition, with a varying degree of muscle weakness appearing between age 18 months and 18 years; most people with type 3 SMA can walk or sit unaided at some point, but many lose mobility over time. SMA affects an estimated 1 in 6,000 to 1 in 10,000 births worldwide,(1),(2) and the incidence varies between different types of SMA. It is estimated that about 100 people are born with SMA per year in the UK, and there are currently between 1,200 and 2,500 children and adults in the UK living with SMA.(1),(2) There are currently no active treatments for SMA, and the condition is managed through multidisciplinary supportive care. Treatment usually follows guidelines from the International Standards of Care Committee for Spinal Muscular Atrophy. Supportive care strategies aim to minimise the impact of disability, address complications and improve quality of life. These may involve respiratory, gastroenterology, and orthopaedic care, as well as nutritional support, physiotherapy, assistive technologies, occupational therapy and social care. References 1. SMA Trust (2017) Spinal muscular atrophy – Key information. Accessed January 2018 2. SMA Support UK (2018) Summary information about SMA. Accessed January 2018.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: Evaluating a rehabilitation protocol following lumbar fusion surgery. A feasibility trial.
Funder: Health Education England

Abstract: This study is designed to assess the feasibility of providing 10 weeks of rehabilitation including advice and exercise after lumbar fusion surgery. Curently it is not clear if this type of approach to surgical after care is possible and/or preferable to usual care. We hope to show that it is possible to provide rehabilitation in this way and that people will agree to participate and attend the classes. We will ask their opinion about the treatment they recieved after surgery to help us plan better care. We anticipate that the rehabilitation will be achieveable and valued by patients.

Lay abstract: This study is designed to assess the feasibility of providing 10 weeks of rehabilitation including advice and exercise after lumbar fusion surgery. Curently it is not clear if this type of approach to surgical after care is possible and/or preferable to usual care. We hope to show that it is possible to provide rehabilitation in this way and that people will agree to participate and attend the classes. We will ask their opinion about the treatment they recieved after surgery to help us plan better care. We anticipate that the rehabilitation will be achieveable and valued by patients.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;6.7 PHYSICAL
Health categories: MUSCULOSKELETAL
Title: Stratification of patellofemoral pain, using MRI structural and biomechanical features, in order to target interventions.
Funder: Health Education England

Abstract: OBJECTIVES: 1. Improve understanding of the patellofemoral joint (PFJ) in health and disease. 2. Classify patellofemoral pain (PFP) patients based on MR structural and biomechanical features. 3 Pilot an intervention based on the classification. DESIGN: 1 An analysis of the 3D shape of the PFJ using novel imaging. 2. A cross-sectional study of the link between symptoms, structure and functional outcomes. 3. A pilot intervention of intensive,targeted physiotherapy treatment. OUTCOMES: A greater understanding of the structure of the PFJ, its influence with PFP and characterisation of sub types.CHAR(13) + CHAR(10)ANTICIPATED BENEFITS: Stratified treatment and potential reduction in the progression to osteoarthritis.

Lay abstract: OBJECTIVES: 1. Improve understanding of the patellofemoral joint (PFJ) in health and disease. 2. Classify patellofemoral pain (PFP) patients based on MR structural and biomechanical features. 3 Pilot an intervention based on the classification. DESIGN: 1 An analysis of the 3D shape of the PFJ using novel imaging. 2. A cross-sectional study of the link between symptoms, structure and functional outcomes. 3. A pilot intervention of intensive,targeted physiotherapy treatment. OUTCOMES: A greater understanding of the structure of the PFJ, its influence with PFP and characterisation of sub types.CHAR(13) + CHAR(10)ANTICIPATED BENEFITS: Stratified treatment and potential reduction in the progression to osteoarthritis.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;6.7 PHYSICAL
Health categories: MUSCULOSKELETAL
Title: Monitoring Scoliosis with 3D Ultrasound
Funder: Health Education England

Abstract: Scoliosis is a three-dimensional deformity of the spine which can worsen as the child grows. Children diagnosed with having scoliosis are imaged with x-rays around twice-a-year. X-rays are ionising radiation and routine use can significantly increase cancer risk. Furthermore, X-ray images are two-dimensional and are limited in the clinical information they provide. This project proposes three-dimensional ultrasound (3DUS) as an alternative method of monitoring patients with scoliosis. By combining conventional ultrasound and motion-tracking technology, 3DUS is able to visualise the complete spine. This aim of this project is to further develop 3DUS and validate it for monitoring and predicting progression of scoliosis

Lay abstract: Scoliosis is a three-dimensional deformity of the spine which can worsen as the child grows. Children diagnosed with having scoliosis are imaged with x-rays around twice-a-year. X-rays are ionising radiation and routine use can significantly increase cancer risk. Furthermore, X-ray images are two-dimensional and are limited in the clinical information they provide. This project proposes three-dimensional ultrasound (3DUS) as an alternative method of monitoring patients with scoliosis. By combining conventional ultrasound and motion-tracking technology, 3DUS is able to visualise the complete spine. This aim of this project is to further develop 3DUS and validate it for monitoring and predicting progression of scoliosis

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Opportunity-Led Research Proposal: TRAC-24
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Single centre randomised controlled trial to assess the effect of the addition of twenty-four hours of oral tranexamic acid post-operatively to a single intra-operative intravenous dose of tranexamic acid on calculated blood loss following primary hip and knee arthroplasty. Primary Objective: The primary objective is to determine if the use of oral tranexamic (TXA) post-operatively for up to 24 hours will confer a reduction in calculated blood loss at 48 hours beyond an intr-operative intravenous bolus alone for patients undergoing unilateral primary total hip or knee replacement (THA/TKA). Secondary Objective: The secondary objective is to determine if the addition of oral TA post-operatively to an intra-operative intranvenous bolus of TXA preduces any change in other measurable parameters as compared to those observed either with an intra-operative intravenous bolus alone or no TXA for patients undergoing unilateral primary THA/TKA.


Research activity codes: 6.4 SURGERY;6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: Enabling Research Award: Development and piloting of a prehabilitation behavioural change and physical activity intervention for fibromyalgia syndrome
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Background: FMS is a chronic pain condition affecting approximately 3% of the population. The condition has a major impact on quality of life with pain, fatigue and sleep dysfunction being the most burdensome symptoms. Physical activity is essential for the management of FMS. Walking interventions have been recommended as an effective form of physical activity for individuals with chronic musculoskeletal pain, but patients find engaging in exercise challenging. Prehabilitation interventions have been successfully used in a range of conditions before surgery to improve rehabilitation outcomes post-surgery. To date prehabilitation it has not been used in FMS. Aim: The aim of the main NETS study is to examine the feasibility of conducting an RCT, using a prehabilitation behavioural change intervention combined with a physical activity (walking) programme, to improve symptoms and physical activity in patients with FMS. Methods: Design: This will be a randomised controlled feasibility study. Participants: Men and women with FMS (n=80) recruited from primary care, rheumatology clinics and patient support groups. Intervention: The intervention will consist of a prehabilitation behavioural change package combined with a physical activity (self-paced walking) programme. It is estimated that the prehabilitation behavioural change intervention will last four weeks (to be determined by the ERA study) and will overcome barriers and facilitate participant ‘buy-in’ to physical activity. The behavioural change intervention will address participants’ capability, opportunity and motivation to engage with physical activity. The physical activity intervention will be a six week, pedometer-driven, walking programme. Participants will receive weekly telephone support. The control group will receive usual care. Outcomes: The primary outcomes from the NETS study will be feasibility outcomes: recruitment rates; acceptability of the intervention; adherence to the intervention; acceptability of the outcome measures including health economic outcomes, treatment fidelity and data for sample size calculation for a future fully powered randomised controlled trial.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: MUSCULOSKELETAL
Title: Predicting Skull Growth in Craniosynostosis for Improved Surgical Treatment
Funder: Royal Academy of Engineering

Abstract: Children with early cranial joint fusion (craniosynostosis) can experience a number of surgeries at early stages of their life. Moazen Lab at the University College London is currently working on optimizing current treatment of this condition using advanced computer simulations. They are also working on a new therapy for this condition that has shown promising results in animal models of this condition.


Research activity codes: 5.4 SURGERY
Health categories: MUSCULOSKELETAL