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Impact: Health and welfare, policy and clinical practice; randomised trial evidence has changed the management and outcome of acute coronary syndromes (ACS) globally.
Significance: Advanced anti-platelet and revascularisation therapies have become standards of care worldwide. There have been large (10-50%) reductions in the death rate from coronary heart disease across Europe. Clopidogrel was the second best-selling drug in the USA in 2011.
Beneficiaries: Patients with ACS, clinical practitioners, NHS and healthcare delivery organisations, policy-makers, pharmaceutical companies.
Attribution: Building on prior studies, Fox (UoE) and colleagues led multicentre randomised controlled trials; international trials were co-chaired by Fox with international investigators.
Reach: Global; guideline changes in Europe and USA; applies to the up to 5% of the population who have ACS.
Over the past 20 years, the University of Oxford's Clinical Trial Service Unit (CTSU), within the Nuffield Department of Population Health (NDPH), has conducted some of the world's largest trials and collaborative meta-analyses of trials of antiplatelet therapy, including aspirin, that have together had a major ongoing and incremental impact on the treatment and prevention of cardiovascular disease. They have helped ensure that antiplatelet therapy is widely used both in the acute care of patients with heart attacks and for the secondary prevention of heart attacks and strokes in high-risk patients. This research has been recognised as the gold standard for international guidelines, and has been instrumental in changing prescribing labelling for aspirin.
Sudden cardiac death causes 4.5 million deaths worldwide each year many of which could be prevented by implantable cardioverter defibrillators (ICDs), but these also carry risks. Research in the groups of Huang and Grace has led to diagnostic assays offering three times the predictive accuracy of current approaches in guiding cardiologists concerning indications for ICD implantation. The assay has been clinically trialled; since 2008, through the trial, the lives of three patients identified by the assay as at high risk were saved. Further work led by Grace and colleagues provided an improved, subcutaneous ICD (SICD); Grace also participated in a US-based clinical trial (NCT00399217) providing the evidence required for FDA approval supporting also later inclusion into NICE guidance. Since 2008 the SICD has been implanted in over 2500 patients in 16 countries.
Approximately 150,000 individuals suffer a myocardial infarction in the UK every year, and world-wide this figure approaches 8 million people every year. The care received by an individual during the acute phase of a myocardial infarction is an important determinant of patient survival. Oxygen therapy has been a mainstay of this acute phase treatment for almost a century.
Research conducted at Surrey highlighted important uncertainties and inadequacies about the safety of oxygen therapy, leading to a follow-up large randomised trial to further investigate this issue, as well as influencing national and international guidelines for emergency cardiac care.
Studies coordinated by the University of Oxford's Clinical Trial Service Unit (CTSU) within the Nuffield Department of Population Health (NDPH) have strongly influenced the labelling of statin medication internationally, treatment guidelines, and the resulting changes in prescribing have contributed to reductions in mortality and morbidity from heart attack and ischaemic stroke in many countries. CTSU's randomised trials and meta-analyses of trials have shown that lowering low-density lipoprotein (LDL) cholesterol safely reduces the risk of heart attacks, strokes and revascularisation procedures in a wide range of people, and work conducted in collaboration with the NDPH's Health Economic Research Centre has provided clear evidence of cost-effectiveness of statins.
Venous Thromboembolism (VTE) is a disease which comprises of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). In 2005, VTE typically caused 25,000 - 32,000 deaths a year, at a typical annual cost to the National Health Service of £640 million (House of Commons Health Select Committee, 2005). However, this disease is mostly preventable (NICE, 2007).
The Autar DVT risk assessment scale was developed to enable clinicians to stratify patients by their risk of developing DVT. The scale exceeded expectations, leading to the introduction of the first mandatory VTE risk assessment tool nationally and shifting the focus of VTE management from reactive treatment (which is resource exhaustive) to very cost effective, proactive, prevention.
The scale continues to be used (both nationally and internationally), and to have impacts that are both financial (cost savings for hospitals) and relate to the wellbeing of patients, both through improved quality of life and reduced morbidity.
A Cardiff researcher has led an International 15 year programme resulting in multiple novel findings which have led to changes in the recommended diagnosis and treatment of acquired haemophilia A (AHA). The research has, for the first time, allowed the comparison of immunosuppressive regimens for inhibitor eradication and comparison of the efficacy of treatment strategies to control bleeds. Studies led directly to the production of UK and International guidelines on the management of AHA with 14 of the 18 specific recommendations in the UK guideline being underpinned by Cardiff-led research.
Impact: Health and welfare; public health studies in Sri Lanka and clinical trials in a cohort of 35,000 pesticide self-poisoning patients have led to the withdrawal of high-dose pralidoxime as a WHO-recommended treatment and bans of three toxic pesticides in Sri Lanka.
Significance: Resultant changes in clinical practice and pesticide regulation have saved 3000 lives in the last four years in Sri Lanka alone; in the rest of Asia many times this as local guidelines and practice have changed.
Beneficiaries: Patients and communities, healthcare providers, policy-makers.
Attribution: Studies designed and led, with international collaborators, by Michael Eddleston, UoE.
Reach: International, particularly Asia, changes in WHO and international guidelines on pesticide use.
Researchers at the University of Manchester (UoM) have made a significant impact nationally and internationally on improving the outcome for children with acute lymphoblastic leukaemia (ALL) (~450 pa in the UK). The changes in clinical practice based on our research are now national standards of care for children with de novo and relapsed ALL in the UK and Ireland. Other international groups have adopted key findings from the results of our frontline trials. Our relapse protocol for childhood ALL underpins European and North American strategy for the management of relapsed disease.
The Acute Infarct Ramipril Efficacy (AIRE) multicentre international trial, conceived, designed, led and coordinated by Leeds was the first to show that use of early angiotensin converting enzyme Inhibitor (ACEI) therapy in patients with signs and symptoms of heart failure after an acute myocardial infarction (AMI) is associated with significantly longer survival and better quality of life. Further Leeds research showed the beneficial effects persisted long-term. The strategy of early initiation of ACEI is now a fundamental and routine part of the management of patients after AMI and has contributed to better survival and quality of life for patients around the world.