NIHRDataInsights/HRCSData huggingface dataset:
Title: Development and assessment of in vitro simulation approaches to intracerebral haemorrhage
Funder: Wellcome Trust

Abstract: Spontaneous intracerebral haemorrhage (ICH) is a frequently occurring cerebrovascular disease of complex pathology representing 10-15% of all strokes. Following the ICH occurrence, the rapid accumulation of blood within the brain parenchyma leads to a disruption of the local nervous system anatomyand to an increase in local pressure; as the entrapped intraparenchymal blood begins to degrade, the blood-element-induced neurotoxicity along with activated hypermetabolic and excitotoxic pathways cause oxidative stress, inflammation, irreversible disruption of the blood-brain barrier, activation of the microglia, cellular oedema and neuronal apoptosis. Unfortunately, to date, no specific clinical pharmacological strategy has been established, while the surgical removal of damaged tissue remains of controversial effectiveness. Taking into consideration the fact that the in vivo experimental simulation of ICH presents important difficulties and limitations, the proposed PhD project aims to: (a) set up reliable in vitro approaches to main pathophysiological aspects of ICH pathology through the use


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE
Title: Predicting language outcome and recovery after stroke (PLORAS)
Funder: Wellcome Trust

Abstract: Informationon the recovery of speech following stroke will be gathered and analysed in order that future stroke patients can be given information on likely recovery of their speech. (A) Stroke patients will have MRI brain scans and be tested on spoken and written language assessments to identify which lesion sites (areas of damage) cause communication difficulties and, for each of these sites, the likely duration of speech recovery. (B) Functional MRI scanning (speech tests completed in-scanner to show areas of brain activation) will be carried out with patients who have made a good recovery of speech. This will provide information on the areas of the brain that take-on speech skills in place of the previous areas, now damaged by stroke. (C) An online database will be created to determine likely speech recovery when the extent of brain damage is known. Clinicians will be able to upload patients brain scans and obtain information about the likely recovery of their patients speech, based on other stroke patients with the same stroke site e.g. 90% of patients who had a stroke in the same region of the brain as you were able to speak well within a year oftheir stroke.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: STROKE
Title: Community-level fatal and non-fatal stroke surveillance: providing the tools for evaluating interventions in hypertension and stroke in sub-Saharan Africa.
Funder: Wellcome Trust

Abstract: In 2010, worldwide 5.8 million people died from stroke, representing 1 in 10 deaths. A disproportionate number of these deaths occurred in low income countries where access to health care is limited. Studies in developed countries show that stroke is largely preventable. In sub-Saharan Africa (SSA) the numbers of new and recurrent stroke and the relative importance of the different factors that increase risk for stroke, are not known. Few SSA countries have vital registration to record the caus e of death, and limited access to sophisticated diagnostics and treatment mean that many stroke patients remain undetected in the community. The proposed research will address these issues. Development of community-level stroke surveillance in Malawi will allow for the first time robust quantification of new and recurrent strokes and current access to care. Pooling cardiovascular risk factor and cause of death data from multiple SSA surveillance sites will strengthen our understanding of the i mportant and potentially modifiable risk factors for stroke in these settings. With an ageing population in SSA this research is urgently needed to inform planning of targeted and cost-effective interventions for the prevention and treatment of stroke and for future allocation of public health services.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: STROKE
Title: Targeted treatment for acute stroke: development of prognostic models and decision support tools
Funder: Medical Research Council

Abstract: Background Although thrombolytic, antithrombotic and antiplatelet drugs are used for the treatment of acute stroke, they can have severe side effects. Better targeting of these therapies could increase their net population health gain by reducing avoidable haemorrhagic and thrombotic events. Aim To develop decision support tools that provide clinically useful guidance and improve patient outcome by better application of existing treatments for stroke. These could be incorporated into the NHS electronic record should they show significant health benefits. Objectives 1. Develop and validate statistical models to predict haemorrhagic and thrombotic arterial and venous events after stroke with data from a number of large cohorts. 2. Determine whether prediction of haemorrhagic events, based on existing clinical and imaging data, has a significant interaction with the treatment benefits of intravenous thrombolysis, heparin and aspirin in large randomised controlled trials. 3. Create a clinical decision tool, based on the prediction models for haemorrhage and arterial and venous thrombosis developed in parts 1-3 4. Pilot the application of the decision tool in stroke practice in NHS Lothian with a view to establishing a larger scale randomised multi-centre evaluation study. Design/Methodology I will develop and validate models for the prediction of haemorrhagic and thrombotic events after stroke in prospective hospital- and community-based cohort studies and randomised controlled trials, from (i) the Stroke Complications and Outcomes Prediction Engine collaboration based in Edinburgh (ii) the Kadoorie Study of Chronic Disease in China and (iii) the Virtual Internet Stroke Archive based in Glasgow To examine the interaction between the results of models predicting haemorrhagic and thrombotic events after stroke and the effect of treatment I will use data from the MRC International Stroke Trial of aspirin and heparin, the Third International Stroke Trial of thrombolysis, and the Chinese Acute Stroke Trial of aspirin. Using tested technology, in collaboration with a group experienced in health informatics, I will develop a tool to present the results of prognostic models as a clinical decision tool. I will evaluate its feasibility in practice, with a view to a larger study. Medical and Scientific Opportunities After stroke, the benefits of antithrombotic and thrombolytic drugs are offset to some extent by an increase in the risk of haemorrhage from the treatment. Better selection of patients for these commonly used treatments could - by focussing treatments on patients most likely to derive net benefit - improve outcome in individual stroke patients, with potentially great population health gains.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: STROKE;BLOOD
Title: Independent Assessment of the Outcome of Detoxification of Male Alcohol Dependent Patients – a Scoping Study Using New Laboratory Based Investigations
Funder: Chief Scientist Office (Scotland)

Abstract: Patients treated for alcohol dependence can be home-patients,out-patients, day-patients or hospital in-patients. In-patients do not have access to alcohol. Day patients visit the hospital daily and can access alcohol against instruction. Local observation suggests that up to 15% of day-patients are noncompliant. Breath alcohol analysis is used, currently, to monitor consumption of alcohol. However, some patients know the limits to which they can consume alcohol and still provide a clear breath specimen. This may be detrimental to outcome. Alcohol abstention and re-exposure in male day-patients, as indicated by urinary ethyl glucuronide concentrations, especially during the first two week period of detoxification, will be compared to a group of male in-patients who do not have access to alcohol. Future research and treatment protocols will be informed by results of this study. Plasma Carbohydrate-deficient Transferrin will be used as a comparator to ethylglucuronide in assessing the severity and continuation of any alcohol use during the period of attempted detoxification. Patients treated for alcohol dependence can be home-patients,out-patients, day-patients or hospital in-patients. In-patients do not have access to alcohol. Day patients visit the hospital daily and can access alcohol against instruction. Local observation suggests that up to 15% of day-patients are noncompliant. Breath alcohol analysis is used, currently, to monitor consumption of alcohol. However, some patients know the limits to which they can consume alcohol and still provide a clear breath specimen. This may be detrimental to outcome. Alcohol abstention and re-exposure in male day-patients, as indicated by urinary ethyl glucuronide concentrations, especially during the first two week period of detoxification, will be compared to a group of male in-patients who do not have access to alcohol. Future research and treatment protocols will be informed by results of this study. Plasma Carbohydrate-deficient Transferrin will be used as a comparator to ethylglucuronide in assessing the severity and continuation of any alcohol use during the period of attempted detoxification.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: STROKE;CANCER AND NEOPLASMS;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Complex systems modelling of alcohol consumption dynamics in the British population
Funder: Medical Research Council

Abstract: Achieving societal benefits by changing the behaviour of individuals is a cornerstone for contemporary public health policy, in key areas such as obesity, smoking and alcohol consumption. However, when examining a potential intervention, the complexity of the implementation environment makes prediction of the resultant population level behaviour change difficult, with traditional research methods used for these purposes (such as regression analysis of randomised controlled trials) rendered infeasible. This project forms a case study on using alternative, inter-disciplinary, methods from the domain of complex systems, for understanding population level behaviour change. The case study aims to describe the character of alcohol consumption, at a population level, in Britain over the last thirty years and to identify causal and contingent explanations for some of the changes in that character. The project will use exploratory data analysis methods across a suite of existing individual level datasets (such as the General Household Survey from 1978 to 2010) to construct a socio-demographic time series describing population level alcohol consumption. Two transitions in the time series will then be examined in detail through computer simulation of established theories from sociology and social psychology (for example, the theory of planned behaviour).


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: STROKE;CANCER AND NEOPLASMS;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Understanding the alcohol harm paradox in order to focus the development of interventions
Funder: Alcohol Research UK

Abstract: Alcohol-related harm and ill-health falls disproportionately on the more deprived sectors of society, while alcohol consumption appears relatively evenly distributed across the social gradient. We will first quantify specific risk estimates associated with deprivation and alcohol consumption, by meta-analysis of scientific reports. We then quantify the extent to which patterns of consumption and/or the underestimation of the impact of very heavy drinkers and abstainers on population averages contribute to this apparent paradox, by i) review of current data and ii) analysis of a new national alcohol consumption dataset (commissioned as part of this study to improve the estimates of total quantity/pattern of consumption). We will investigate the contribution of co-morbidities that are linked to deprivation. Finally we arrive at deprivation-specific attributable fractions to help identify areas most at risk. The results will inform the development


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: STROKE;CANCER AND NEOPLASMS;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Alcohol policy modelling and evaluation
Funder: Medical Research Council

Abstract: The aim for this research programme is to lead a step-change in capabilities for robust scientific appraisal of new and existing alcohol policy interventions. Controlling alcoholic affordability and availability are amongst the most effective policy options available to governments. These policies can be unpopular with consumers and industry, so it is imperative that decisions are based on sound evidence. However, important knowledge gaps remain and with policy stakeholders and international advisors, we identified priority areas for scientific advance. 1. New evidence to inform policy appraisal: We propose data acquisition, data analysis and evidence synthesis in areas where new evidence is critical: (a) Market response to pricing policy; (b) Relationship between heavy episodic drinking and harms in different settings; (c) Variability in individuals? consumption patterns over time; (d) Time lag between policy, consumption and harm changes; and (e) Socio-political context effects that may moderate policy effectiveness. 2. Building of a model that considers taxation and availability policy options: Taxes are the only price-based interventions currently operating in most Western economies. The health and social impact of a range of taxation options (eg. the current ?duty escalator?; differential taxation by alcoholic strength) will be appraised. Similarly, we will appraise availability policies, which remain almost unexamined due to lack of integrated data on outlet opening hours and density. 3. Building a dynamic model: Current models are static, assuming a ?stay steady? baseline level of consumption and harms, rather than dynamic i.e. accounting for trends over time. We propose a major model revision to account for recent and long-term underlying trends in alcohol prices, income, consumption and harm. 4. Policy evaluation/model validation: Many methodological advances in our recent modelling have come about because ?an answer was needed? to real policy options. We propose to incorporate a 3 year programme of policy appraisal that is responsive to emerging stakeholder needs. We will produce annual reports on evidence synthesis, model developments, validations and policy appraisals, to enable researchers and UK and international policy stakeholders to view and use developing work. A systematic comparison of model predictions with real changes in consumption/harm will also be undertaken. We bring together UK and international alcohol policy researchers, and experts in evidence synthesis, policy modelling, industrial economics, health economics and public health information and expect that our work programme will lead to major advances in evidence-based alcohol policy decision making. Strong links with stakeholders have been established to facilitate exploitation.


Research activity codes: 4.3 INFLUENCES AND IMPACT;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: STROKE;CANCER AND NEOPLASMS;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Adaptation and feasibility study of a family and social network intervention for young people who misuse alcohol and drugs
Funder: Department of Health (England)

Abstract: Design: (i) Development phase followed by (ii) Pragmatic randomised feasibility study including economic evaluation.Setting: Two community services for young substance misusers: one delivered by Lifeline in Birmingham in the West Midlands; the other provided by dna services for young people in Newcastle. Target population: Young people aged 14 to 18 referred for drug and/or alcohol problems to the two services involved in the research. Health Technologies Being AssessedStudy intervention: Social Behaviour and Network Therapy (SBNT) is an intervention developed in the UK by members of our research group shown to be effective with harmful drinkers (UKATT research team BMJ 2006) and recommended by recent NICE guidance. We believe that SBNT can be adapted to the youth context with great potential as a clinically and cost effective intervention which can be readily implemented in services for young people. We believe that involving young people who have been through drug and alcohol services in the design of the intervention will give us insights into its acceptability and effectiveness. We will also draw on the literature in this field in adapting this intervention. Treatment as usual: Young people in this arm will continue to receive usual care delivered by the two services. Measurement of cost and outcomesWe will measure the variability in primary and secondary outcome measures collected to inform the outcomes for a future definitive trial. Measures will be taken by research fellows at baseline 3 and 12 months follow ups after random allocation. The primary outcome measure will be level of drug and alcohol use measured through the Timeline Follow-back (TLFB) interview validated with adolescent populations (Dennis et al. Addiction 2004). Family-based approaches have the potential to impact on other facets of young people’s lives and we will measure a number of family psychological and social risk factors as well as therapeutic alliance that has also been linked with retention and outcomes. In order to explore cost-effectiveness in a full trial intervention costs will be measured using local service costs; QUALY changes will be measured through EQ-5D at baseline 3 and 12 month follow-up. We will also measure criminal justice involvement and use of social services.Sample sizeSixty participants in total 30 randomised to receive adapted SBNT and 30 treatment as usual. Each site will recruit 30 participants (15 in each condition). This number will allow us to establish rate of consent engagement in treatment and drop out. All participants will be followed up at 3 and 12 months for qualitative interview and measurement of outcomes. Project staff will also be interviewed.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: STROKE;CANCER AND NEOPLASMS;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Addressing non-response in health survey data to refine alcohol consumption estimates in Scotland
Funder: Medical Research Council

Abstract: We propose to examine how representative the respondents to the 1995, 1998 and 2003 SHeSs are in terms of alcohol-related hospitalizations (SMR) and deaths (GROS) to inform the improvement of survey-based estimates of alcohol consumption. Linked SHeS-SMR/GROS data (to 2010; maximum follow-up 15 years) will be compared with 1991 and 2001 census records, mortality and hospital admission data for the entire population. We shall: 1. Compare SHeS-SMR/GROS and general population rates of alcohol-related hospitalizations and deaths; 2. Determine the probability of alcohol-related hospitalization/death in the survey non-responders; 3. Calculate the number of non-respondents for each socio-demographic category (age, sex, area deprivation and health region); 4. Generate observations for non-responders with the corresponding alcohol-related hospitalization and death probabilities in each combination group; 5. Use multiply imputation* - the recommended means of substituting values for missing data items - for unknown alcohol consumption estimates under the assumption that the consumption data are 'missing at random' (MAR)* given socio-demographic category and alcohol-related hospitalization/death; 6. Modify the alcohol consumption imputations to represent likely differences in association between alcohol consumption and alcohol-related hospitalizations and deaths between observed and missing consumption data using a pattern mixture model approach which assumes that the consumption data are 'missing not at random' (MNAR)* given the observed data. We shall look separately at each survey round to assess the effects of non-response level. An advanced correction procedure will be developed for application to other surveys with record-linkage capacity. Further work may include integration of national sales data to further refine consumption estimates. * For technical detail, see the Statistical methodology section of 3.3 in the Case For Support document.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: STROKE;CANCER AND NEOPLASMS;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Alcohol Policy Interventions in Scotland and England: APISE
Funder: Medical Research Council

Abstract: Heightened awareness of the extent and range of the global burden of disease from alcohol has led to new commitment, at national and international levels, to make policy change. While a body of research evidence exists on the effectiveness of specific alcohol policy interventions there are very significant shortcomings in the evidence base. There is a need for a long term-monitoring study, with a strong baseline data collection, which can then regularly monitor responses to policy changes as they occur. This proposal is for the first two waves of such a study: Alcohol Policy Interventions in Scotland and England (APISE). New alcohol policy interventions are actively being considered in both Scotland and England, providing an opportunity for a natural experiment to evaluate the impact of the different policies which are likely to be put in place in each country. The study also has an international component with parallel studies being conducted in a number of other countries. The study aims to yield robust evidence on the effectiveness and mechanisms of macro-level alcohol policy interventions. Three linked stages of research include an audit of alcohol control strategies in each country, exploratory research with adult drinkers and a longitudinal survey. The baseline survey, planned for 2012, will recruit a cohort of 2000 adult drinkers in England and 2000 in Scotland. The cohort follow-up survey will take place 12 months later. The survey will be conducted by telephone and collect data on a range of policy related variables (proximal variables), moderating and mediating variables as well as behavioural outcomes. By including proximal variables, for each policy, there is potential to trace the effects of each policy, over time, to their ultimate effects on behaviour through different mediational routes and thus strengthen the ability to attribute impact to specific policies.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: STROKE;CANCER AND NEOPLASMS;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL