Find out about the winners of the 2017 grant round:
- Dawkins & Strutt grant to assist research into multimorbidity in an aging population
- Doris Hillier grant to assist research into rheumatism and arthritis
- HC Roscoe grant to promote research into the elimination of the common cold and/or other viral diseases of the human respiratory system
- Helen H Lawson grant to promote research into novel technologies and/or organisational systems to assist in patient care, primary care or public health
- Josephine Landsell grant to assist research into the field of heart disease
- J Moulton grant to assist research into idiopathic thrombocytopenic purpura (ITP)
- Kathleen Harper grant to assist research into the impact of working pressures on the medical profession
- Margaret Temple grant to assist research into schizophrenia
- T P Gunton grant to assist research into public health relating to cancer
- The James Trust grant to assist research into asthma
- The Scholarship grant to assist research comparing risks of injury and mechanisms of injury across sport in children and adults
- Vera Down grant to assist research into neurological disorders
You can find out more about the winners and their projects by clicking through the tabs below.
Dawkins & Strutt
Dr Jackie Buck RN, BSc (Hons), MSc, PhD
University of East Anglia
Dr Jane Fleming BA (Hons), RGN, MPhil, PhD
Investigating multimorbidity in a population-based study of older old age: the Cambridge City over-75s Cohort (CC75C)
More of us are living into ‘older old age’: the number of people aged 90 or older has almost tripled in three decades. Many diseases develop with age but modern healthcare has improved survival, so growing numbers of very old people are living many years with health conditions. Recent guidelines stress the importance of taking account of their needs, but because living so long is quite new, there is little information about very old age.
This project aims to use information already gathered through a long-running study of ageing (CC75C) from people who were already aged at least 75 when this began in 1985. Their generous willingness to help research, answering interview questions every few years in repeated surveys until the last person had died, has created a unique resource that can help plan for our ageing population by answering some of the questions health and care services are asking: How commonly are very old people living with various different conditions and especially with more than one condition (known as ‘multimorbidity’)? What support are they relying on from medication, health/care services and family? What are their experiences of living with multiple conditions and their priorities? What factors affect older old age multimorbidity?
Dr Oladapo Joseph Ogunbayo
Polypharmacy associated with non-prescription medication use among older adults with multi-morbidity.
Multimorbidity, the co-occurrence of two or more chronic conditions, is increasingly common among older adults (≥65 years). Most older people will require one or more medicines to manage and live well with their chronic condition(s). Polypharmacy, which is the concurrent use of multiple medicines (usually five or more) can be problematic, especially among older adults with multimorbidity as it increases the risks of non‐adherence to treatment, toxicity, interactions, poor quality of life, hospitalisations and death.
The use of prescribed medicines is the main predictor of polypharmacy but there are increasing concerns about self-medication with over-the-counter, herbal and other medicines (e.g. those bought over the internet) that have not been prescribed. The adverse consequences of polypharmacy associated with these non-prescribed medicines may be even greater for older, frail adults who are already on numerous prescribed medicines and may be experiencing cognitive and functional impairments and other geriatric syndromes.
The project will involve systematic review of current evidence, data analyses of population level data to explore factors and patterns associated with non‐prescribed medicines use and variables such as sociodemographic, disease and health status and health service use. The findings will provide evidence for clinicians and policymakers and help to develop strategies that go beyond review of prescribed medicines.
Dr Venkat Reddy MB BS, MRCP & Dr Maria Jose Leandro MD, PhD
University College London
Defining blood markers to stratify individuals with Lupus for targeted therapies
Lupus is a rare, complex condition where our immune system causes damage to vital organs such as the kidney and the heart. Lupus characteristically affects different people in dissimilar ways. Removing a type of white blood cell known as ‘B cell’, transiently with a biological agent known as rituximab, helps a majority of the people treated for active lupus, temporarily, whereas some others respond less well.
Our preliminary work has identified that the levels of specific markers associated with lupus activity may either reduce or remain high despite treatment with rituximab in different patients. In this project, we propose to investigate the potential for another marker detectable in blood samples from patients that may help us group individuals into those likely to respond to B-cell targeted therapies to help reduce the use of treatments that are less likely to be effective in some individuals, who may benefit from alternative targeted therapies and improve the prospects for treatment with right drug for the individual with lupus.
H C Roscoe
Dr Simon Drysdale BSc (Hons), MB BS, MRCPCH, PhD & Professor Andrew Pollard FRCPCH, PhD, FMedSci
University of Oxford and Oxford Radcliffe Hospitals
Microbial biomarkers of severe respiratory syncytial virus (RSV) infection in infancy in the respiratory microbiome
Respiratory syncytial virus (RSV) is the leading cause of severe chest infections in infants worldwide; up to 30,000 infants are hospitalised in England and Wales each year. The aim of this project is to identify whether certain bacteria that are normally present in the human respiratory tract, are linked with an increased likelihood of developing severe chest infections when infants are infected with RSV. Using existing stored nasal samples, we will analyse the composition and density of the normal bacteria colonising the noses of infants with severe RSV infections and controls with mild RSV upper respiratory tract infections from the UK and Kenya. Samples collected during acute infection and at recovery will be analysed. Infants will be followed up for 2-3 years to assess for chronic lung conditions (e.g. asthma). We will use molecular techniques (next generation sequencing) to identify bacteria, and statistical analysis to determine whether certain bacteria are associated with severe RSV disease and chronic lung conditions. This study will potentially help identify infants at risk of severe RSV disease and who, therefore, are most likely to benefit from medications to prevent RSV infection, which are very expensive.
Helen H Lawson
Dr Ian Austin Male MSc MRCP MBBCh
Sussex Community NHS Foundation Trust
Establishing Sensitivity of a Child Social Communication Assessment Tool
NICE recommends that diagnosis of autistic spectrum disorder requires a multidisciplinary assessment, which our previous research has shown requires 14 hours of professional time, costing £800 per child, to complete. Most UK child development centres adopt a two-stage process, with an initial “screening” clinic determining the need for a full diagnostic assessment. Families often wait a long time for this. Improving decision making at initial contact has the potential to improve the patient journey and reduce costs.
We have developed an app incorporating tests used to assess whether a child shows autistic patterns of thinking, for example whether they can recognise facial expressions, or “put themselves in someone else’s shoes” (theory of mind). These are presented as a pirate adventure game played with the child in clinic. The aim is for this to provide a picture of the child that could be used alongside parental history and school questionnaire to decide which children need a full diagnostic assessment. With encouraging early pilot data, including positive parental and child acceptability, we plan to determine the ability of the app to distinguish a “typically developing” (control) sample of local schoolchildren from children diagnosed with autism spectrum disorder.
Dr Katherine Lodge MB BChir MA MRCP(UK) AFHEA
University of Cambridge
Hypoxic Upregulation of Neutrophil Microparticle Release Drives Endothelial Damage and Dysfunction
Cardiovascular disease is the leading cause of death worldwide. Low oxygen levels found in patients with lung diseases, e.g. emphysema, can damage the cells which line blood vessels (endothelial cells), thereby contributing to atherosclerosis and heart disease. Atherosclerotic fatty deposits narrow blood vessels, reducing local oxygen levels and further increasing heart disease risk.
Circulating inflammatory white blood cells (neutrophils) promote this process, and I have previously shown that low oxygen levels make neutrophils far more destructive and prone to damage blood vessel endothelial cells. Neutrophils release small packages (microparticles) containing proteins, which affect the functions of other cells and may also contribute to blood vessel damage.
During this project, I will investigate how low oxygen levels affect neutrophil microparticle release and whether these low-oxygen microparticles damage coronary artery cells. I will also study patients with emphysema, who have low oxygen levels, increased neutrophils and increased risk of cardiovascular death, and see if they have higher levels of potentially damaging microparticles in the blood. In the short term I hope to find markers of heart disease risk and, in the longer term, identify potential new treatments to delay atherosclerosis progression.
Professor James Charles Connor Moon MBBS MRCP MD
UCL & Barts Health NHS Trust
Dark Blood Late Gadolinium Enhancement − A Novel Quantitative Biomarker for Investigating Lamin DCM
Dilated cardiomyopathy (DCM) is probably the most common serious genetic heart disease. Modern medicine is entering an era of genetics. We now know that around 10% of DCM is caused by a specific mutation - Lamin. This is far more serious than usual DCM with a really high risk of heart failure and sudden death. But we are not there yet - not everyone gets genetics. We need better imaging predictors for early diagnosis and to predict risk and who should get the genetic testing. This matters because there is a treatment - putting in an implantable defibrillator (ICD).
The UK leads on cardiac MRI - the best imaging test for cardiomyopathy. We will develop tests for lamin in heart muscle using scar imaging and mapping. Working with the National Institutes of Health in the US we will develop these for Lamin, their diagnostic and predictive power, to roll out these tests to the NHS to try and quantify and predict lamin for better patient care and outcomes.
Dr Charlotte Ann Bradbury MA (Oxon), BMBCh, FRCP, FRCPath, PhD &
Dr Richard William John Lee BMedSci, BMBS, MRCS, MRCOphth, PhD
University of Bristol and University Hospital Bristol NHS Trust
The development of a blood test to predict responses to steroid treatment in patients with immune thrombocytopenia
When a group of patients with Immune thrombocytopenia (ITP) (Bristol, UK) were asked to help prioritise research questions, they identified steroid effects and the trial and error approach to ITP treatment as the most impactful problems from their perspective. High dose steroids are the commonest first treatment for ITP but side effects are very common and for some patients their ITP does not get better. Currently, there is no way to predict the success of steroid treatment prior to administration.
We have preliminary data demonstrating that the response of immune cells extracted from ITP patients to steroid treatment in the laboratory (outside the body) is different from patients who do and don’t get better when taking steroids. This forms the basis of the hypothesis that it is possible to predict a patient’s response from a blood test. This could help personalise treatments, ensuring steroids are only given to patients likely to benefit, whilst more efficacious treatments are given earlier to those expected to not respond. This project aims to confirm this finding by testing a larger number of patients with ITP. In parallel, we are testing a new technology using special blood tubes (TruCulture) that assess in detail immune cell responses at the molecular level. These tubes have potential to be adapted into blood test that could be used in the "real world" for patients with ITP.
Dr Nichola Cooper MD, MBBS, FRCP, FRCPath
Imperial College NHS Trust
Understanding clonality in T cells in immune thrombocytopenic purpura
Immune thrombocytopenia (ITP) is an autoimmune disorder that can occur at any age. The main feature of ITP is a reduced platelet count (this is called thrombocytopenia). The main function of a platelet is to make blood clots and to stop bleeding. Patients with ITP are therefore at risk of bleeding, which can be life threatening. The cause for the low platelet count is not fully understood. In the majority of patients it is felt that the immune system attacks the platelet causing premature destruction. However, it is not clear why the immune system attacks the platelet. Rarely, there are some cases of familial ITP, where more than one person in the family has ITP. For this reason we believe that some patients have a genetic predisposition to get ITP while other patients acquire a disease over time. Modern genetic techniques can allow us to dissect these possibilities. For this project we will look at whether the main cells in the immune system (the T cell) acquire a change in the DNA (called a somatic mutation), which make them more likely to attack the platelet, or whether there is an expanded clone of cells which recognise the platelet as foreign.
Dr Quentin Anthony Hill BSc (hons), MBChB, MRCP, FRCPath
Leeds Teaching Hospitals NHS Trust
The impact of Fc gamma receptor polymorphisms on treatment response in adult patients with primary immune thrombocytopenia.
Platelets are small cellular fragments that circulate in the blood and help blood to clot. Immune thrombocytopenia (ITP) is an autoimmune condition that results in low platelets and can result in life-threatening bleeding. ITP is often caused by the immune system producing antibodies that bind platelets. The antibodies then bind to receptors on scavenger cells (phagocytes) in the spleen and liver, which remove the antibodies and bound platelets.
Variation in the genes that code for phagocyte receptors (polymorphisms) is known to affect receptor expression and how well they can bind antibodies. We aim to determine whether particular polymorphisms are more common in ITP patients compared with healthy controls. Also whether having certain polymorphisms will predict a better response to ITP directed treatments (rituximab and immunoglobulins). This could influence clinical care if we can identify individuals who have a high or low chance of responding to these expensive treatments.
Dr Anli Yue Zhou MBChB, MA, MRCP
University of Manchester
The determinants and effects of stress in junior doctors working in the National Health Service
Previous research has shown that junior doctors as a group demonstrate higher levels of stress compared to senior doctors, which can have a negative impact on patient care. In order to reduce the risk of psychological distress and subsequent mental ill-health in junior doctors, more needs to be known about the potential remediable determinants of their occupational stress.
The proposed study aims to develop a clearer understanding of what specific occupational factors contribute to stress in junior doctors. This will involve a mixed methods approach consisting of 3 phases. Firstly, focus groups will be undertaken to understand and identify occupational determinants of stress (i.e. the stressors) in junior doctors and then summarised into a model. Subsequently, the model will then be used to develop and validate an instrument that objectively measures occupational stressors. The instrument will also be used to investigate the relationship between the stressors and the adverse effects of stress on junior doctor wellbeing such as burnout and psychological co-morbidity.
By identifying and measuring relevant occupational stressors, these can be monitored and provide new knowledge to develop targeted organisational interventions to reduce the negative impact of stress in junior doctors working in the National Health Service.
Dr Adam Ala Jaffer Al-Diwani MA BMBCh (Oxon) MRCP (UK) & Dr Sarosh Irani DPhil MRCP
Oxford University Hospitals
Fuel for the psychotic fire: lymph node and cerebrospinal fluid B-cell analyses to investigate NMDAR-antibody-associated psychosis
Psychosis is a common mental health condition. People can experience muddled thinking, develop paranoid beliefs, and hear unpleasant voices. Causes are complex, but in some patients the immune-system may contribute.
Our immune system normally makes antibodies to remove infection - but sometimes these antibodies confuse the body for infection. If this is the brain, they can cause “encephalitis”, causing seizures and memory loss as well as psychosis. Medications which lower antibodies usually help these patients improve.
Up to 10% of people with psychosis have similar antibodies in their blood but do not clearly have encephalitis. The most common target is the NMDA receptor, which allows messages to be transmitted between brain cells and is crucial to normal thought processes.
Our research studies the immune cells that make these antibodies. Alongside routinely obtained samples, we will sample lymph nodes in the neck using the safe and well-tolerated approach of ultrasound-guided fine needle aspiration. This award will help fund laboratory materials and equipment. We hope to better understand the immune system in this group of patients, which may help develop targeted immune treatments in the future.
Professor Oliver Howes
King’s College London
Cardiac dysfunction in schizophrenia: a potential mechanism underlying the excess of cardiovascular disease in the disorder?
On average people with schizophrenia die 20 years prematurely, and heart disease is a major contributor to this excess mortality. Schizophrenia is associated with inflammation and antipsychotics have direct toxic effects on heart muscle, both of which could impair cardiac function to increase cardiovascular risk even in the absence of metabolic or lifestyle risk factors. However, it remains unknown if schizophrenia is associated with cardiac dysfunction in the absence of antipsychotic treatment. Our study aims to determine if there is cardiac dysfunction in people with schizophrenia without cardiovascular risk factors, and to define the role of antipsychotics in this process. We will use Cardiac Magnetic Resonance imaging to measure cardiac function in two cohorts of individuals with schizophrenia, one taking antipsychotics, and the other antipsychotic naïve, and compare them with matched healthy controls. The study findings could have major and immediate clinical implications for patients as they could identify new intrinsic and/or antipsychotic related mechanisms that could underlie the excess cardiovascular mortality in schizophrenia, as well as the potential need for cardiac screening in schizophrenia.
Professor Philippa Oakeshott MA MD FRCP FRCGP
St George’s, University of London
Prevalence of carcinogenic human papillomavirus in mouthwash samples from 400 sexually active, hard to reach, ethnically diverse teenagers: proof of concept study
Cancer producing (“carcinogenic”) human papillomavirus (HPV) causes around 250,000 cases of head and neck cancer each year worldwide. However, the natural history of carcinogenic HPV in the mouth and throat is not well understood, and we do not know how common it is in young people in the community. In the UK, adolescent girls are offered vaccination against carcinogenic HPV types 16/18 to prevent cervical cancer. We aim to explore the frequency of carcinogenic HPV in the throats of sexually active, ethnically diverse teenagers attending inner city colleges.
We recently obtained mouthwash samples, and information about HPV vaccination and oral sex, from 204 participants (median age 17 years, 75% from ethnic minorities) in our NIHR-funded “Test n Treat” chlamydia screening trial. We will test these samples for carcinogenic HPV. We will measure the frequency of HPV vaccine types 16/18 in mouthwash samples and rates of reported HPV vaccination.
Most young people (70%) practice oral sex, but many do not realise they can get sexually transmitted infections in their throat. If we find an estimated ≥4% have carcinogenic HPV 16/18 in mouthwash samples, this could reinforce public health messages about safer sex and HPV vaccination.
Professor Jesper Lagergren MD, PhD
King’s College London
Cancer risk following obesity surgery
Dr Sarah Crisp MB, BChir, PhD, MRCP
University of Cambridge
Identification of Pathogenic Antibodies in Stiff Person Syndrome
Antibodies are usually part of the body’s defence against infections and cancer, but in autoimmune diseases they can mistakenly attack healthy cells. Antibodies can cause neurological diseases by binding to proteins on the surface of nerve cells and disrupting the normal communication between them. Patients with these antibodies often develop very serious neurological illnesses, but can be treated by removing antibodies from the blood or suppressing their production.
Stiff person syndrome (SPS) is a disabling neurological condition causing muscle rigidity and painful spasms. Most patients with SPS have antibodies to an enzyme in inhibitory neurons (GAD65). However, it is unlikely that these antibodies are directly responsible for SPS because the enzyme they target is inaccessible unless the neurons are already damaged. Nonetheless, at least some patients respond to antibody-suppressing treatments suggesting that they have other antibodies that bind to accessible proteins on the surface of neurons and cause disease. My work aims to find disease-causing antibodies in patients with SPS. This will facilitate the development of novel tests to diagnose SPS and may help to identify patients who are likely to respond to antibody-suppressing therapies.
BMA Foundation for Medical Research
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Corporate development, British Medical Association, Tavistock Square, London, WC1H 9JP
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