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Trauma is a rapidly increasing global healthcare problem which is predicted by the World Health Organisation (WHO) to overtake infectious disease globally by 2020. The discovery of the acute coagulopathy of trauma (uncontrolled bleeding) and the subsequent establishment of the clot stabiliser tranexamic acid (TXA) as a treatment for this condition has led to a change in national and international trauma management protocols. British armed forces and the US military implemented the use of the drug soon after the results were published. Every injured British or American soldier now receives this treatment. The use of TXA has been included in national and international guidance for trauma care.
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 discovery of an early Acute Traumatic Coagulopathy (ATC, a syndrome of abnormal clotting after trauma) by Professor Brohi's team in 2000, and subsequent work building on that pivotal discovery, has led to [A] a new understanding of why patients bleed to death after severe injury and resulted in [B] a fundamental change in resuscitation strategy for acute bleeding patients (`Damage Control Resuscitation') that has led to [C] a 250-300 per cent improved survival in massively bleeding trauma patients. Discovering the character and mechanism of ATC has led to [D] new research in diagnostics and therapeutic opportunities to further improve outcomes. These rapid changes have led to [E] new forums for professional education and [F] improved public understanding of science and medicine.
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.
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.
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 wellbeing; translation of a clear evidence base for reducing red blood cell use in intensive care and surgery into guidelines and changed clinical practice.
Significance: A 20% reduction in overall UK red blood cell usage between 2002-2012, saving the NHS approximately £100M annually; 7000 fewer patients are exposed to red cell transfusion annually, saving 500 lives.
Beneficiaries: Patients in intensive care units; the NHS and healthcare delivery agencies.
Attribution: Studies were led by Walsh at UoE with NHS and Canadian collaborators.
Reach: 7000 patients per year, UK-wide; incorporation into international guidelines.
Neonatal extracorporeal membrane oxygenation (ECMO) is a complex procedure of life support used in severe but potentially reversible respiratory failure in newborn infants. In 1993 researchers in Leicester carried out the first and, to date, only large-scale randomised trial comparing the value of ECMO with other means of life support. The trial, with follow-up research at 4 and 7-year intervals, has shown ECMO to be a life-saving and cost-effective treatment, and has led to the establishment of a centrally funded neonatal programme that is estimated to have saved around 340 lives in the UK alone. In 2013 the University remains internationally renowned in the field of ECMO research, and since 2009 Glenfield Hospital has been home to the world's largest ECMO centre for the treatment of newborns, older babies and adults. The trial is still held up by advocates of fair clinical trials as an example of how evidence should translate into practice and policy.
Impact: Health and welfare; a large randomised controlled trial (third International Stroke Trial (IST)-3) and meta-analysis determined that the thrombolytic agent recombinant tissue plasminogen activator alteplase is a long-term effective treatment for acute ischaemic stroke in a wide range of patients.
Significance: Thrombolysis would result in 1488 more stroke patients being alive and independent per year in the UK.
Beneficiaries: Stroke patients, the NHS and healthcare delivery organisations, the UK economy.
Attribution: The IST-3 trial was led from UoE (Sandercock), with UoE (Wardlaw, Dennis) and University of Sydney (Lindley) colleagues.
Reach: Worldwide. Applicable to 4 million stroke patients per year; guidelines changed in Europe, N America, Asia, Australia.
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.