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Research conducted at UCL/UCLH over the last 20 years has enabled the identification of adults with acute leukaemia who are most likely to benefit from the use of stem cell transplantation, i.e. those with acute leukaemia in first remission. The treatment is highly intensive, potentially toxic and expensive high-dose chemotherapy followed by haemopoietic stem cell transplantation, and is inappropriate for some patients. The work has made a major contribution to the development of guidelines worldwide for the treatment of this disease. Improved patient selection for transplantation results in improved survival, less toxicity with improved overall quality of life, and a more appropriate use of NHS resources.
Three national, multicentre randomised controlled trials and associated studies during a 20-year research programme on abdominal aortic aneurysm (AAA) led by Imperial College researchers have altered international practice. The United Kingdom Small Aneurysm Trial (UKSAT) set the threshold for intervention at 5.5cm to repair AAAs. Population screening programmes and guidelines in Europe (UK, Sweden and Europe as a whole), Australia and the United States are based on these data. The results from EndoVascular abdominal Aortic Repair (EVAR) trials have informed international audits, guidelines (including NICE) and task forces in the same countries.
The University of Oxford's International Subarachnoid Aneurysm Trial (ISAT) changed clinical practice worldwide by showing that endovascular coiling is a more effective and safer treatment than neurosurgery following subarachnoid haemorrhage, with fewer complications and improved quality of life. Subarachnoid haemorrhages account for 1 in 14 strokes and are caused by bleeding in and around the brain; approximately 85% occur when cerebral aneurysms rupture. ISAT was the first trial to compare neurosurgery, or neuroradiological endovascular coiling in patients with ruptured cerebral aneurysms causing acute subarachnoid haemorrhage.
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.
Warfarin is an anti-coagulant drug prescribed to tens of millions of people in the UK and US who are at high risk of developing blood clots. Because individual sensitivity to warfarin varies in the population there is a risk of overdosing the drug and causing serious bleeding and even stroke in many people when starting treatment. In 1999 researchers at Newcastle University were the first to demonstrate a statistically significant link between a person's genotype and the appropriate dose of warfarin. In 2010 the US Food and Drug Administration (FDA) mandated inclusion of a table of dose recommendations based on genotype in the warfarin prescribing information leaflet accompanying the drug. Newcastle research forms the basis of the 2009 international standard algorithm for gene-guided dosing of warfarin. This approach has been adopted by large US medical centres and the FDA states that it will prevent 17,000 strokes a year in the US.
Every year in the UK, 150,000 heart attacks are caused by coronary artery occlusion (blockage); worldwide, the figure is 17 million, according to the World Health Organization (WHO). Since 1993, the Leicester Interventional Cardiology group has been at the forefront of research to determine how best to manage such patients. Its findings have been incorporated into official UK (2008), European (2008, 2012) and US (2008) guidelines and have helped to change the way coronary heart disease and heart attacks are treated, with the number of patients treated with primary angioplasty doubling between 2008 and 2011. By guiding service provision, supporting industrial innovation and informing clinical practice, the Unit has contributed to improved healthcare and outcomes for thousands of heart patients. Overall, one-month mortality according to European figures has fallen from 15% to 4% between 2008 and 2013.
Severe Limb Ischaemia (SLI), in which there is reduced blood flow to the leg(s), is the commonest cause worldwide of gangrene and limb loss. The BASIL trial, led by Professor Andrew Bradbury at the University of Birmingham, was the first (and remains the only) randomised controlled trial to investigate whether surgical bypass or endovascular (`keyhole') treatment is best at relieving symptoms and preventing amputation and/or death in patients with SLI. The outcomes of the study have been of worldwide interest, and the recommendations put forward by the team have been endorsed by a number of high profile clinical organisations. These findings are also nowincorporated within a series of national and international guidelines on SLI.
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.
Malignant pleural mesothelioma (MPM) is a treatable but incurable cancer that originates in the cells lining the lungs. Over 14,000 people worldwide are diagnosed annually with MPM. Antifolates are often used in cancer therapy, but side effects are a major issue. A retrospective analysis of cancer trials and phase 1 trial of MPM patients, carried out by Newcastle in collaboration with Eli Lilly Pharmaceuticals, determined that plasma homocysteine levels were a good predictor of drug toxicity in cancer patients treated with the antifolate pemetrexed, and that this drug was well tolerated by patients with low homocysteine levels. It was also determined that pemetrexed treatment should be supplemented with vitamin B12 as well as folic acid, to reduce drug toxicity. Ultimately, this permitted the continued development of pemetrexed, which otherwise would have been too toxic for clinical use. It is now the only licensed drug for MPM treatment in combination with platinum-based chemotherapy.
COPD affects up to 3.5 million people in the UK and costs the NHS £700m pa. Over the last 15 years, research by Professor Calverley and colleagues at the University of Liverpool (UoL) has impacted significantly on the care of COPD patients. Specifically, this group showed that routine testing of COPD patients for the presence of bronchodilator reversibility was unreliable and did not predict clinical outcomes. This changed international guideline recommendations in 2007 and the Quality Outcomes Framework payments to GPs in 2009. They showed that oral corticosteroids accelerated recovery from exacerbations and that anti-inflammatory drugs, whether inhaled corticosteroids or PDEIV inhibitors, reduced exacerbations by 25% with a subsequent fall in the number and length of hospitalisations. This led to changed NICE guidance for corticosteroids in 2010 and drug registration with EMA and FDA for the PDEIV inhibitor treatment in 2011. Treatment in UK and Western Europe has changed as a result of this research.