NIHRDataInsights/HRCSData huggingface dataset:
Title: STRIDE - Strategies To increase confidence InDependence and Energy. Cognitive behavioural therapy-based intervention to reduce fear of falling in older fallers attending a community falls service: Therapy development and randomised controlled trial
Funder: Department of Health (England)

Abstract: Design: Phase 1: Pilot (consecutive-cohort type) study to develop a novel cognitive behavioural therapy intervention (CBTI) tailored to older patients with fear of falling (FoF) per MRC complex intervention development model. Phase 2: Parallel-group patient randomised controlled trial (RCT) of the novel CBTI plus usual care vs. usual care alone in patients with FoF.Setting: Single community-based multi-disciplinary falls service.Target population:Consecutive community-dwelling fallers both sexes >60 years with excessive or undue FoF per Falls Efficacy Scale – International (FES-I) score of >23 (Delbaere K et al Age Ageing 2010). No upper age limit; exclusion: cognitive impairment (MMSE <24).Health technologies being assessed:Phase 1: Development of the CBTI model During patient interviews a CB model will distinguish predisposing precipitating and perpetuating factors with CBTI development targeting perpetuating factors. Falls service healthcare assistants will then be trained in CBTI to maximise its uptake and generalisability. Phase 2: RCT Patients will be randomised to individual CBTI (weekly for 8 weeks plus usual care in the falls clinic with 6 month reinforcement session) or control groups (usual care only). Follow-up: 12 months to assess the longevity of CBTI’s effects. Process evaluation of the trial guided by May’s Normalisation Process Theory throughout to provide a guide to implementation and integration in clinical practice.Measurement of costs and outcomes:Primary outcome measure: Fear of falling: FES-I.Secondary outcome measures: 1. Falls (“unintentionally coming to rest at a lower level”) and injury rates (fall diaries): Number of a) patients falling; b) falls; c) fractures and significant soft tissue injuries. 2. Hospital Anxiety and Depression Scale. 3. Quality of life: WHOQOL OLD EQ-5D SF-6D scales. 4. Social Participation and Social Isolation: Social Disconnectedness and Percieved Isolation Scales. 6. Impact on function: Short Physical Performance Battery functional reach handgrip strength. 7. Economic evaluation: costs and benefits of CBTI related to health social care and personal resource use; extra cost per QALY gained by CBTI. 8. Process evaluation: qualitative evaluation involving key service/training personnel and a purposive sample of clients in each phase.Outcome data: collected at baseline (pre randomisation) following CBTI (at 8 weeks) and 6 and 12 months post-intervention as well as assessment of harms level of social care and dependency. Weekly symptom diaries (validated in similar populations) will record falls and injuries.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: INJURIES AND ACCIDENTS;MENTAL HEALTH
Title: Over three years to study computerised training of working memory (Cogmed RM) in children who have survived a traumatic brain injury: A phase II randomised controlled trial.
Funder: Action Medical Research

Abstract: Background Each year around 280 children per 100,000 require at least 24 hour’s hospitalisation following a traumatic brain injury (an injury which has been caused by excessive force, often caused by car accidents or falls). Childhood traumatic brain injuries are associated with emotional, behavioural, cognitive, and social difficulties. Children who survive a traumatic brain injury can also have problems with their working memory. This is the memory which is used to hold and manipulate information in the mind for short periods of time, such as remembering a telephone number. These memory difficulties can affect learning at school and at home, and in the long term affect a person’s ability to find a job and live independently. The research project The researchers aim to find out whether a computerised working memory training program can improve memory performance in children who have survived a traumatic brain injury; and if so, whether improvements are also found on school-based learning tasks and life at home. Children who take part will be invited to complete some paper and pencil tasks, as well as complete a variety of working memory tasks in a computerised game environment. It is hoped that the findings from this research study will lead to larger studies across the UK, and will inform routine NHS practice for children who have survived a brain injury.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: INJURIES AND ACCIDENTS;MENTAL HEALTH
Title: Regulating neuroplasticity to restore upper limb and hand function after spinal cord injury
Funder: Medical Research Council

Abstract: Spinal cord injury (SCI) results in profound disability, and there are no regenerative therapies. Most SCIs occur in the cervical region and recovering hand function is the highest rated patient priority for improving quality of life. Chondroitinase ABC (ChABC) is a potent neuroplasticity-promoting agent that breaks down inhibitory components of the extracellular matrix, enabling new connectivity and functional recovery after SCI. The proven pre-clinical benefits of ChABC have been demonstrated by multiple labs worldwide, making it a leading candidate for clinical development. In recent work we have applied a novel, regulatable gene therapy approach, which enables temporal control of ChABC transgene expression and the ability to switch the gene on and off multiple times in vivo, effectively opening "windows of neuroplasticity". We demonstrated recovery of skilled hand function in cervical contused adult rats when treated for 2 months with the gene continuously on. Here, we will use inducible ChABC vectors to evoke neuroplasticity and address critical steps that remain before this therapy can be translated to the clinic: Aim 1: We will explore the potential for "training neuroplasticity" by varying the gene induction regime alongside high-intensity reach and grasp training to determine the optimal regimen for recovery. Aim 2: We will determine whether late-stage neuroplasticity can enable recovery in chronic SCI, and examine patterns of gene expression and biodistribution with acute and chronic delivery. Aim 3: We will use chemogenetic silencing to determine the motor pathways that mediate recovery, and utilise human and primate SCI tissue to determine key targets of ChABC and whether their spatio-temporal distribution is conserved across species. This work will provide crucial translational and mechanistic data needed for advancing a candidate regenerative gene therapy into a clinical treatment to enable recovery of hand function after SCI.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.2 CELLULAR AND GENE THERAPIES
Health categories: INJURIES AND ACCIDENTS;MUSCULOSKELETAL
Title: Assisted Living Technologies for Older People at Home: creating a knowledge base for businesses and commissioners about falls and dementia patients
Funder: Innovate UK

Abstract: AKTIVE is directed by Professor Sue Yeandle and is being developed by four partners: CIRCLE at the University of Leeds (lead partner); the Oxford Institute of Population Ageing (Oxford University); Tunstall Healthcare (UK) Ltd; and Inventya Solutions Ltd. These partners are working with a wider AKTIVE consortium, includingexperts from medicine, design, risk, disability and ergonomics, telecare commissioners in two local authorities and agencies representing older people, carers and care workers. It is funded from June 2011-May 2014 and investigates: • What are the characteristics of older people (especially with dementia and / or susceptibility to falls) who use telecare? • How is telecare equipment used in private homes? • How and in what ways can unpaid carers benefit from the use of telecare in older peoples' homes? • What are the barriers to the adoption of telecare for individuals, families and service providers? • Does telecare offer opportunities to improve job design and quality for care workers, providers and commissioners? • What are the main features of the market for telecare and what can be done to enhance innovation and improve take-up?


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: INJURIES AND ACCIDENTS;NEUROLOGICAL
Title: A randomised control trial of rivastigmine versus placebo for improving gait stability in patients with Parkinson’s disease with a past history of a fall
Funder: Parkinson's UK

Abstract: Research question: Does rivastigmine improve gait stability, balance and freezing of gait in patients with Parkinson's disease (PD) with a past history of a fall? Aim: To evaluate the role of cholinesterase inhibitor therapy on gait in patients with PD. Objectives: To undertake clinical trial to assess the effect of rivastigmine on gait and balance, attention and executive function, falls and freezing of gait. Design: A single centre, double blind placebo controlled randomised control trial. Methodology: Patients with idiopathic Parkinson's disease without dementia and with a history of having fallen will be recruited and enrolled. Participants will be randomised in a 1:1 allocation. The intervention group will receive rivastigmine and the control group, placebo. The primary outcome measure is gait variability and assessments will be performed at 0,4,24 and 28 weeks. Falls follow up will continue for 1 year. or control and receive placebo. The main analyses will be performed using the intention to treat principle. We will use multivariable linear, logistic and proportional hazard regression models as appropriate. Implications: Gait variability, a marker of gait stability, is a surrogate marker of falls risk. Predictive models of falls risk will be validated along with novel methods of assessing freezing. The findings will facilitate scientific understanding of the aetiological mechanisms underlying axial symptoms It will support or refute the role of cholinesterase inhibitors for falls in PD.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INJURIES AND ACCIDENTS;NEUROLOGICAL
Title: MICA: Potential of P2X7 receptor antagonism to attenuate the adverse consequences of neurotrauma (PROTECT)
Funder: Medical Research Council

Abstract: Traumatic brain injury (TBI) is the leading cause of death and disability in the first four decades of life; despite obvious need, there is no approved drug treatment. Activation of the excitatory P2X7 receptor in the brain by relatively high levels of ATP - as likely occur in TBI - promotes an inflammatory environment that may add to the volume of brain damage above that from the primary insult. Also, animal models of neurotrauma respond favourably to P2X7 receptor antagonists. Hence, our hypothesis is that the inflammation and secondary brain damage that evolves hours/days after the primary insult is reduced by blocking the P2X7 receptor. We propose this will tip the balance away from the pro-inflammatory environment to improve clinical outcome. We will test this hypothesis by evaluating the tolerability of the clinical stage P2X7 receptor antagonist, CE-224,535, in patients with TBI and the ability to reach pharmacologically relevant concentrations in the injured brain (also monitoring any drug impact upon neuroinflammation and clinical outcomes). The project progression will be milestone driven, based upon outcomes from Work Packages (WP) addressing the following questions: WP1: Do primary microglia from patients with TBI express functional P2X7 receptors that promote the secretion of pro-inflammatory cytokines/chemokines? WP2: Is oral CE-224,535 well tolerated in TBI patients and does the drug gain sufficient access to the brain to potentially reduce the inflammatory environment and improve clinical outcomes? Whilst minimal outputs from the project include an enhanced understanding of the role of the P2X7 receptor in the inflammation storm that is associated with TBI, positive clinical data from the project will encourage further development of P2X7 receptor antagonists towards meeting the unmet considerable clinical need for a drug to improve the clinical outcomes following TBI.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INJURIES AND ACCIDENTS;NEUROLOGICAL
Title: Endoplasmic reticulum, Protrudin and Axon Regeneration
Funder: Medical Research Council

Abstract: The application focuses on the role of endoplasmic reticulum (ER) in axon regeneration. This concept comes from previous work on protrudin. This scaffolding molecule brings together molecules and components that promote regeneration. Our recent work shows that it has a very strong effect on promoting regeneration of mature cortical axons in vitro and retinal axons in vivo. Protrudin has VAP-A and a hairpin domain that both fix it to the ER. Deletions of each of these domains renders protrudin ineffective at promoting regeneration. As cortical neurons mature in vitro and lose their ability to regenerate, ER in the distal axons declines. Axons that regenerate (immature CNS neurons, sensory neurons) have abundant ER in their axons. Protrudin restores ER in mature axons, and only ER-recruiting forms of protrudin promote regeneration. It is surprising that ER has not been a focus of regeneration research. Its many functions in calcium regulation, phospholipid synthesis, direction of vesicle trafficking, endosome production etc. make it a strong and novel candidate. The application aims to determine the role of ER recruitment, caused by protrudin and several other ER-shaping molecules, in regeneration. First ER morphology in regenerating and non-regenerating axons will be studied. Next, several molecules that should increase or decrease axonal ER will be tested, and effects on regeneration measured in regenerative and non-regenerative neurons. Two key ER functions are phosphoinositol synthesis and formation of ER-plasma membrane contacts. The role of these in regeneration will be tested. Successful treatments will be tested in vivo for optic nerve and corticospinal tract regeneration. The results will inform current strategies in the lab to promote CNS axon regeneration.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.2 CELLULAR AND GENE THERAPIES
Health categories: INJURIES AND ACCIDENTS;NEUROLOGICAL
Title: The roles of the alarmin HMGB1 in injury and repair of white matter after traumatic brain injury
Funder: Medical Research Council

Abstract: Objective 1. I will utilise the facilities in place at Cardiff University, including the established human tissue biobank & in vitro scratch & drop-weight models of TBI (1) to validate & expand our findings in animal tissue demonstrating HMGB1's detrimental effect on post-traumatic oligodendrogenesis. Human cortical monolayer and 3D cultures (control and injury) will be examined for HMGB1 cellular localisation and nuclear-to-cytoplasmic translocation using immunocytochemistry and western blotting. Cell death will be assessed using propidium iodide and oligodendrocyte precursor proliferation will be measured in EdU experiments. Oligodendroglial maturation will be quantified with immunostaining, Scholl analysis, and western blots. I will assess the impact of trauma upon myelination using immunocytochemical metrics described previously (2). Objective 2: I will assess in our model of TBI how modulators of HMGB1-signalling affect human oligodendroglial injury & recovery. These will include antagonists of HMGB1 release, (Ethyl Pyruvate) and its receptors (BoxA, Glycyrrhizin). Objective 3: I will utilise similar protocols to collect human cortical tissue from TBI patients undergoing contusionectomy. ELISAs will confirm if HMGB1 and its receptors are present in these samples, which I will quantify & correlate with patient outcomes compared to control tissue samples. I will apply HMGB1 modulators to these post-traumatic human cortical cultures, as per objective 2. I will therefore examine the effects in post-traumatic cortical human tissue of HMGB1-signalling on oligodendroglial injury/repair, and determine if those effects can be manipulated to improve human oligodendroglial population survival and recovery. 1. Kumaria A. In Vitro Models as a Platform to Investigate Traumatic Brain Injury. Alt. to Lab. Animals. 45:201-211 (2017) 2. Stangel et al. Achievements & obstacles in the design of remyelinating therapies for MS. Nat Rev Neurol. 12:724-754 (2017)


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INJURIES AND ACCIDENTS;NEUROLOGICAL
Title: Understanding the evolution of pathology after traumatic brain injury using advanced magnetic resonance imaging
Funder: Wellcome Trust

Abstract: Traumatic brain injuries result from falls, road traffic collisions, assaults or military activities. They are expected to affect every second person at some point in their lives and are a major cause of disability and death. Different people’s brains seem to react differently to similar injuries. Some people recover whilst others continue to deteriorate even after the initial event, for example by developing early-onset dementia. We plan to use magnetic resonance images to study how the structure of the brain changes in the days to years after injury. The types of images we use (in particular diffusion tensor imaging) can reveal fine details that are invisible on conventional imaging. We will study approximately 1000 patients who had repeated scans from 72h to two years after injury, which is the largest database of its kind. Importantly, we will not assume that everyone’s brain is the same but will strive to identify sub-types of response to injury. We will then compare how these structural changes relate to patients’ symptoms and see if we can predict early after injury which recovery trajectory a patient is likely to follow.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INJURIES AND ACCIDENTS;NEUROLOGICAL
Title: Development of a screening instrument for Dysphagia following Acute cervIcal Spinal cord injurY: identification of current practice and validation of a tool (DAISY)
Funder: Department of Health (England)

Abstract: Swallowing problems are a life threatening complication for patients who sustain a high spinal cord injury. They cause chest infections, breathing problems, poor nutrition and a high risk of death. A tool to assess swallowing problems will be developed, by consensus from an expert panel and tested for validity. The tool will become part of the acute care pathway to enable earlier diagnosis and management of swallowing problems for cervical spinal cord injury patients. Current practice by intensive care unit staff and SLTs will be surveyed and patients interviewed about their own early experiences to ensure relevance of the tool.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INJURIES AND ACCIDENTS;ORAL AND GASTROINTESTINAL
Title: Determining the lasting impact on the developing epigenome by gestational toxic exposures
Funder: Medical Research Council

Abstract: The overall aim of this research programme is to understand the mechanisms by which toxic insults induce changes to epigenetic pathways. In particular, work will be directed towards understanding how exposures during mammalian gestation result in lifelong changes to regions of the epigenome. These exposures can be separated into two groups, environmental exposures, and pharmacological interventions. Murine pregnancies will be subjected to chronic toxic insults and analysis will be performed on the exposed offspring. A series of mouse reporter lines will be utilised that enable the longitudinal in vivo tracking of epigenetic change. This is achieved through the knocking in of a bioluminescent reporter into the 3’ UTR of a series of imprinted genes, whose expression is regulated in a well-defined epigenetic, parent-of-origin specific manner. A series of studies have demonstrated that these genes can be sensitive to gestational environmental exposures, resulting in mis-expression of the reporter in exposed offspring. These methods will be employed in addition to more traditional genomics techniques to identify regions of the genome that are exquisitely sensitive to toxic insult. Particular focus will be played to the persistence of any changes that occur as the exposed offspring age, and whether these changes are transmitted to subsequent generations. Mechanistic information will be garnered through comparison of diverse toxic insults and their impact on sensitive regions of the genome. These studies will provide novel information on the extent and lasting impact of toxic exposures during pregnancy. With the mechanistic information. In the longer term this research will help in the development of clear and well-informed Pregnancy Prevention Plans for tested drugs, particularly for those where there are no or only limited alternatives which remains a priority.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INJURIES AND ACCIDENTS;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: An assessment of the impact of pressure ulcers on health related quality of life and development of a preference-based, Patient Reported Outcome Measure (PROM)
Funder: Department of Health (England)

Abstract: Pressure ulcers are wounds that occur mostly on the sacrum (buttock area) and heels. They can have a profound impact on a person’s quality of life. Interventions to prevent and treat pressure ulcers need to be able to include a value for the state of health of having a pressure ulcer. This value can be measured using Patient Reported Outcome Measures (PROMS): these are questionnaires asking patients about their health and impact of their condition. The aim of this project was to develop a specific PROM to use for people who develop pressure ulcers. The project took place in both the acute hospital and community setting. Patients and clinical staff were interviewed in order to obtain descriptions of how having a pressure ulcer impacted on health and quality of life. The interviews were digitally recorded and analysed to identify key issues and themes. The main findings from the interviews was that the impact of having a pressure ulcers depended on how it had been caused and could be masked by the impact of other illnesses. In addition, patients in hospital described that having a pressure ulcer was less important than why they were admitted to hospital: their focus was on getting home. One common issue was that having a pressure ulcer led to a feeling of a loss of dignity due to having to have intimate areas examined and treated. The findings from the interviews were used to produce a questionnaire that could be used within evaluations of treatments and interventions for pressure ulcers. Patients in both the hospital (n= 273) and community (n= 130) were surveyed. Patients had a range of comorbidities and the presence of a pressure ulcer was associated with a significant decrement in quality of life. Dignity was shown to be measurably affected by the presence of a pressure ulcer.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: INJURIES AND ACCIDENTS;SKIN