NIHRDataInsights/HRCSData huggingface dataset:
Title: The CRASH-3 Trial: Tranexamic acid for the treatment of significant traumatic brain injury.
Funder: Medical Research Council

Abstract: The CRASH-3 trial is a multi-centre, randomised placebo controlled trial of the effects of the early administration (within 8 hours of injury) of tranexamic acid on death, disability and vascular occlusive events in patients with acute traumatic brain injury. A total of 10,000 adult TBI patients who fulfil the eligibility criteria will be randomised to receive either TXA or matching placebo. All adults with TBI who are within eight hours of injury, with any intracranial bleeding on CT scan or who have a Glasgow Coma Score (GCS) of 12 or less, and do not require immediate blood transfusion for extra-cranial bleeding, will be eligible for inclusion. The main criterion is the doctor's 'uncertainty' as to whether or not to use TXA in a particular patient. This pragmatic approach allows us to see whether TXA works in real-life conditions. The primary outcome is death in hospital within one month of injury (cause of death will be described). Secondary outcomes are disability and other patient orientated outcomes; vascular occlusive events (myocardial infarction, pulmonary embolism, deep vein thrombosis); stroke; seizures; neurosurgical intervention and days in intensive care. We are working with an established network of hospitals that has successfully delivered many global trauma trials (CRASH-1 and CRASH-2 trials). Nigeria and Pakistan were major contributors to these trials and a research partnership has been established with them to help co-ordinate the CRASH-3 trial. LSHTM will build clinical trials research capacity in these settings by providing oversight, training and guidance in conducting clinical trials to the highest global standards.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INJURIES AND ACCIDENTS
Title: Introduction of the Cardiff Trauma Pack in Road Traffic Accidents in Namibia for use by First-Responders: An early phase study
Funder: Medical Research Council

Abstract: Road traffic injury is the world's eighth leading killer causing 1.2 million deaths annually. We have produced an ultra-low-cost Trauma Pack for developing world use, by non-specialists in the first or 'golden' hour after trauma, when lives are saved. Our solution is also lightweight, compact, and tackles transportability, standardisation and usability. It enables organised delivery of first response by users with limited knowledge or skill. The pack meets or exceeds the performance of existing products and reduces purchase cost by over 80%, through materials selection and product design. The Trauma Pack provides intuitive, life-saving equipment and easily understood instructions, using the global standard C/ABCDE care sequence. It addresses the transportation of unstable victims, ensuring non-expert users stabilise before transportation. A co-creative approach with International Red Cross and Royal Centre for Defence Medicine means the pack was developed with a clear understanding of contexts, end users, function and usability. Symbiosis IP Ltd identified that parts of the pack, or the whole, maybe protectable through patent application and design rights. Namibia has one of the worst Road Traffic Accidents problems in the world. Prof Hall has a major successful collaboration in Namibia which will be mobilised for the study. An early-phase study of Trauma Pack utilisation in Namibia will develop educational material to train First-Responders in its use, with educationally, ethnographically and linguistically appropriate materials. A subsequent 6 month study of 200 pack uses will assess for the major study : a. usability of the pack in the Namibian context; b. correct pack content for Namibia and its First-Responders; c. best Trauma Pack community/responder placement to ensure optimum accessibility ; d. that the pack performs successfully in the field. These results will enable the design of a major population intervention study of the Trauma Pack


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: INJURIES AND ACCIDENTS
Title: Health in a changing climate: the dynamic challenge of snake bite in South Asia
Funder: Medical Research Council

Abstract: Snakebite is a neglected tropical disease (NTD) and despite being less well studied, has a far greater impact than many other NTDs. There are estimates of up to 120,000 deaths per year globally with major morbidity also resulting from limb damage or renal failure. This burden predominantly affects the rural poor, particularly agricultural workers and subsistence farmers in lower-middle income countries (LMICs) in the tropics/subtropics. There is considerable seasonal and geospatial variation of snakebite because of complex interactions between human behaviour, climate, geography and other factors affecting snake distributions. Burden estimates are difficult: health system statistics are flawed, national surveys are logistically difficult to do and complex variation makes it difficult to estimate national burdens from small local studies. Variation also means that changing environmental, ecological and human conditions could influence this burden. This new collaboration brings together experts in snakebite, epidemiology, ecology and environmental change science to develop spatially explicit predictions for snakebite risk in a changing climate or land-use environment. We will first update our 2008 global burden of disease study and risk factor analysis to provide the global and regional context for subsequent national-scale research. Then, using Sri Lanka as a study system, we aim to better understand the spatial and temporal variation in snake bite by focusing on the human-snake contact rate. To do this, we will a) develop high resolution distribution models for important venomous snake species and identify how their distributions are shaped by environmental variables, b) generate a snake bite exposure index and validate it with existing detailed epidemiological data on snake bite, envenoming and mortality patterns and c) undertake activity profiling to assess the impact of climate change and land-use on snake and human behaviours and upon these models.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);4.4 POPULATION SCREENING
Health categories: INJURIES AND ACCIDENTS
Title: MICA: Monitoring wound status using multi-parameter optical fibre sensors
Funder: Medical Research Council

Abstract: A recent analysis of the health economic burden of wounds (Guest et al BMJ Open 2015;5:e009283) highlighted that ~2.2 million wounds were managed by the NHS in 2012/2013 requiring annually 18.6 million practice nurse, 10.9 million community nurse, 7.7 million GP and 3.4 million hospital outpatient visits. The annual NHS cost of managing these wounds is £4.5-5.1 billion (~4% of the entire NHS budget). We propose to develop a wound dressing incorporating inexpensive optical fibre sensors (OFS) which will monitor parameters associated with wound healing. The sensors will be fabricated in thin (~100um diameter), lightweight, low cost optical fibres incorporated into a wound dressing. The new dressing could have a significant impact on NHS costs and patient care. It will enable clinical interventions to take place promptly but only when required, thus improving wound care and reducing the number of NHS appointments. Studies will involve clinic based evaluation followed by a community based study of patients with chronic wounds. Design, regulatory, statistics and health economics expertise will help to support development of a valuable, safe tool that is acceptable to patients and clinicians.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INJURIES AND ACCIDENTS
Title: Developing a cocktail of enzyme inhibitors to universally treat haemotoxicity caused by snakebite
Funder: Medical Research Council

Abstract: Snakebite is a neglected tropical disease that kills ~100,000 people each year. Currently, many different antivenoms are used to treat victims, as their efficacy is limited to the snake species used for manufacture. Antivenoms exhibit poor specificity, high incidences of adverse reactions and high treatment costs, and there is therefore an urgent need to dramatically improve therapy for snakebite victims. The most common lethal snakebite pathology is haemotoxicity, which is the result of enzymatic venom toxins causing haemorrhage, coagulopathy and/or hypotension. Here we propose using small molecules (enzyme inhibitors) to generically inhibit the functional activity of these toxins. Our proof of concept data demonstrates that enzyme inhibitors offer the potential to generically neutralise haemotoxic venoms (i.e. irrespective of snake species, unlike antivenom) both in vitro and in in vivo models of envenoming. We will apply a variety of in vitro biochemical enzyme/functional assays to characterize the activity of ten medically important snake venoms (both crude and fractionated venom), before assessing their neutralisation by a panel of enzyme inhibitors. Because of venom variation, we will require a combination of inhibitors to effect cure, and thus we will next design mixtures of effective inhibitors before re-assessing venom neutralisation. Finally, the two optimal mixtures will be used in in vivo studies to assess their preclinical efficacy against each of the venoms in comparison with existing commercial antivenoms. We anticipate that our inhibitory mixtures will exhibit superiority over antivenom by neutralising venom lethality irrespective of the snake species tested and at lower therapeutic doses, resulting in a single, generic, therapy for treating haemotoxic snakebites worldwide. The resulting inhibitory mixture would be eminently translatable into a commercial product by offering economies of scale, improved safety profiles and reduced treatment costs.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;5.2 CELLULAR AND GENE THERAPIES
Health categories: INJURIES AND ACCIDENTS
Title: Interventions for treating wrist fractures in children
Funder: Department of Health and Social Care

Abstract: Wrist (mainly of the distal radius) fractures are the most common fractures in children: around 3/1000/year. Severity ranges from the stable torus/buckle fractures, featuring a bulge but not break to the bone cortex, to unstable completely displaced fractures in both forearm bones. Buckle fractures account for an estimated 500,000 emergency department attendances a year in the UK (NICE 2016). The impact, including financial, for time off work or making other arrangements for care, on families can be considerable. Traditional treatment is cast immobilisation with surgery reserved for more seriously displaced fractures. For buckle fractures, the key issue relates to whether immobilisation is overly protective and removable splints or bandages can be used instead. These should allow earlier return to function and avoid the inconvenience and expense of returning to clinic for cast removal. NICE 2016 identified treatment of buckle fractures as a priority topic and a new trial commissioned by the NIHR (17/23). Other key issues relate to extent of immobilisation and when surgery is required for more serious displaced fractures that could, especially where the growth plate is involved, have lifetime implications where treatment is unsuccessful. So far, we have identified 29 trials that test 12 comparisons.


Research activity codes: 6.3 MEDICAL DEVICES;6.4 SURGERY
Health categories: INJURIES AND ACCIDENTS
Title: 2013 Doctoral Fellowship: Heart Rate Variability Biofeedback in Young People with Autism - a Feasibility Study
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: This feasibility study is a randomised trial using two parallel groups. It will assess the effectiveness of a heart rate variability biofeedback intervention in reducing mental health symptoms as indicated by anxiety, depression, attention problems, and behaviour problems in young people with autism aged 11-18. Participants will be randomly allocated to one of two groups, a biofeedback treatment group or a conventional treatment control group. The treatment group will receive training in biofeedback. Control participants will receive training in standard relaxation techniques. Assessment will involve parents and teachers and participants all rating mental health symptoms and levels of autism symptoms in the participant via questionnaire reports. In addition in vivo recordings will be taken in a clinic setting of participant’s heart rate variability and eye tracking whilst they complete a series of visual tasks prior to training in either the biofeedback or conventional treatment. Both groups will be reassessed again on all measures at 12 weeks, and again at 24 weeks from the beginning of training. It is hypothesised that the trial of biofeedback will reduce levels of measured mental health symptoms and that this reduction in symptoms will be larger than that in the conventional treatment group. The measurable outcomes from this study will provide new information about the feasibility of using this new type of intervention with this population by identifying recruitment strategies needed; assessing ethical issues, as well as testing the effectiveness of this intervention, and its sustainability over time.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: INJURIES AND ACCIDENTS
Title: Effectiveness and safety of calcium channel blockade for organophosphorus and carbamate anticholinesterase insecticide poisoning (CCBOC study)
Funder: Medical Research Council

Abstract: Current treatment for anticholinesterase poisoning is often ineffective, resulting in tens of thousands of deaths. Presynaptic acetylcholine (ACh) release is controlled by Ca2+ flow into the terminus. Reduction of the pre-synaptic Ca2+ load, using Mg2+ or calcium channel blockers, may reduce ACh release and overstimulation that causes acute toxicity and delayed respiratory failure. Eight small clinical studies, of varying quality, have suggested that MgSO4 may reduce mortality and intubation/ventilation (meta-analysis odds ratios: 0.55 [95%CI 0.32-0.94] and 0.52 [0.34-0.79], respectively). We aim to set up an open pragmatic RCT in four Bangladeshi hospitals to determine whether addition of intravenous MgSO4 or nimodipine to standard therapy (supportive care, atropine and for OPs pralidoxime) reduces deaths after acute OP or carbamate poisoning. Primary outcome will be in-hospital all-cause mortality; secondary outcomes will include % intubated and duration of ventilation. In these hospitals, 11% of patients die under usual care. The anticipated treatment effect is a reduction to 7% i.e. an absolute decrease of 4% with either MgSO4 or nimodipine. This reduction would be sufficient to have either treatment adopted as the new standard of care. The study would have 80% power at 2.5% level of significance to detect a 4% reduction from 11% with 1,022/arm. We will use group sequential design to conduct formal interim analysis, increasing the sample size to 1,033/arm. The hospitals admit 1800 patients/year; we expect to recruit around 70% as in our previous trials. The RCT will provide definitive data concerning the effectiveness of these affordable, widely available therapies and potentially introduce the first new treatment for OP anticholinesterase poisoning for 50 years. Improved therapy offers the opportunity to save tens of thousands of lives amongst some of the world's poorest populations and reduce the familial and community heartbreak of suicide.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INJURIES AND ACCIDENTS
Title: Developing an integrated community mobilisation package to prevent childhood injuries in rural Bangladesh
Funder: Medical Research Council

Abstract: Aim: to develop and assess the feasibility and acceptability of an integrated package of community mobilisation interventions in preventing childhood injuries in rural Bangladesh. Potential interventions: The main intervention will be an integrated package of community mobilisation activities - combining the strengths of community action groups (CAGs), of household-visits in providing tailored practical advice, and of mass media in generating awareness in catalysing social action on the barriers to taking action. Target population: all caregivers in the community with children aged 0-5 years. Methods: The study aim will be achieved though qualitative formative research and engagement with local and national stakeholders. Specifically the following activities will be conducted: - Phase 1: Inception: engagement with stakeholders, agree on project objectives and research plan and build potential theory of change. - Phase 2: Formative research: conduct qualitative individual and group interviews with different stakeholders in order to gain in-depth understanding of attitudes and practices regarding childhood injuries and prevention. - Phase 3: Design: design the intervention package using findings from Phases 1 and 2. - Phase 4: Pre-testing: the designed intervention and its components will be piloted at a small scale, for example in one village using individual and group interviews with caregivers and delivery agents, as well as using the Trials of Improved Practices (TIPs) approach. - Phase 5: Dissemination: findings will be shared with the stakeholders in a one-day meeting in Dhaka, and through academic papers as well as conference presentations to wider audiences.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INJURIES AND ACCIDENTS
Title: MRC Transition Support CDA Yanlan Mao
Funder: Medical Research Council

Abstract: My CDA has investigated the role of mechanical forces in tissue growth, morphogenesis, and wound healing. I have made a number of key discoveries during my CDA, including the function of actomyosin in buffering mechanical forces to maintain tissue shape, and the role of tissue fluidity in wound healing. These have been published in high impact journals. However, the bulk of my CDA research is yet to be published. Several of these are critical for future grants, such as a Senior Fellowship, as they provide essential evidence to show that I can lead and manage an interdisciplinary research team and conduct research and publish at the highest international level, key criteria for Senior Fellows. The progress of these manuscripts has been hindered mostly by my 2nd period of maternity leave, which has taken place in the last 8 months. Inevitably my research momentum was reduced during these last 8 months as I simultaneously attend to a newborn. It would thus be physically and mentally impossible to apply for a Senior Fellowship, which would start by the end of my CDA in May 2020. I need additional time to regain my research momentum and give me sufficient time for the creative processes necessary to successfully apply for a Senior Fellowship. Due to the slow turn around of grant applications, without some immediate transition support, I would lose all my current lab members, which would have a massive detrimental effect on the lab that I have worked so hard to build, and I would lose even more momentum, which would further reduce my chances of successfully obtaining a Senior Fellowship. The aim of this Transition Support is therefore for me to regain research momentum, retain key current research staff, publish the remaining papers from my CDA in the most efficient and timely manner, and gather enough preliminary data to successfully obtain a Senior Fellowship.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: INJURIES AND ACCIDENTS
Title: Chitetezo: Improving adolescent road safety and reducing road traffic collisions.
Funder: Medical Research Council

Abstract: Current approaches to prevent road traffic collisions (RTC) among adolescents are not working. We have developed and feasibility tested a novel peer-led prevention intervention (Chitetezo) to improve adolescent road safety, through changing behaviours and reducing RTC around schools in Malawi. Our overall study objective is to investigate if Chitetezo can reduce RTC around schools in Malawi. The study has an explanatory mixed-methods design. It incorporates both process evaluation and quasi-experimental elements across 10 schools. We will conducted four interconnected work packages (WP). In WP1 we will use participatory co-design methods to refine intervention components and hypothesised programme theory using recently gathered feasibility data. We will co-develop intervention materials for WP2. Schools will be purposively selected based on geographical dispersion, proximity to tarmacked roads, high traffic density and frequent collisions. Participants (n=8 per school) will be purposively selected using maximum diversity sampling. A mixed-method multiple case study process evaluation, informed by realist evaluation methods, will be undertaken, with each school being a case. In WP3 we will investigate Chitetezo's impact on behaviour, road safety infrastructure, and RTC. Three complementary data collection approaches will be used: i) a citizen science project with adolescents to evaluate the level of non-reported RTC; ii) participatory mapping activities to capture local knowledge about road traffic risks, and road safety behaviours; and iii) an interrupted time series (ITS) to analyse RTC around participating schools using an ongoing routine dataset (from 2003). The effectiveness of Chitetezo will be evaluated using a comparative interrupted time series (ITS) analysis. Data from each WP will be combined in a triangulation matrix to investigate convergence and divergence to answer the overall research objective. WP4 will focus on dissemination and legacy planning.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: INJURIES AND ACCIDENTS