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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.
Before the Hypertension in the Very Elderly Trial (HYVET) it was not clear whether people aged 80 and over with hypertension should receive antihypertensive treatment. The over 80s are one of the fastest growing groups in society and are at high risk of hypertension and its sequelae due to age. HYVET demonstrated benefit of treatment including reduced mortality and cardiovascular comorbidity. Guidelines around the world for the treatment of hypertension have changed as a result. In the UK it is proposed that the Quality Outcomes Framework (QOF) for GPs now includes those over 80 and uses the target blood pressure used in HYVET.
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.
Imperial College researchers have pioneered the implementation of therapeutic hypothermia to improve survival of neonates following perinatal asphyxia.
Following their programme of clinical research to prove feasibility, Professors Azzopardi and Edwards led the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), a multicentre, randomised trial investigating the effects of total-body cooling for 72 hours in babies with asphyxial encephalopathy from a lack of oxygen at birth. This work demonstrated that infants in the cooled group had an increased rate of survival without neurologic abnormality. This work has influenced public policy and healthcare provision, through the implementation and audit of therapeutic hypothermia nationally and internationally. In the UK, cooling therapy is now carried out in 1000- 1500 cases annually (Data reported to the UK National Register of Cooling). Cooling following perinatal asphyxia is now standard of care in most resource rich and intermediate countries.
Impact: Health and welfare; a UK clinical trial of uterine artery embolisation (UAE), with five-year follow-up, defined the risk- and cost-benefit of UAE versus surgery.
Significance: The trial informed guidelines/recommendations internationally and changed clinical practice. Women worldwide can now make an informed choice about their treatment; economic factors have been quantitated.
Beneficiaries: Uterine fibroid patients, the NHS, healthcare providers.
Attribution: G. Murray, UoE, developed and delivered innovative trial methodology; clinical aspects led by University of Glasgow.
Reach: UK guidelines; worldwide (Australia, USA, Europe) effect on clinical practice that will impact up to 25% of women.
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.
Prior to the change in WHO recommendations which occurred following this study many patients in Africa and other developing countries were receiving an inferior regimen for the management of tuberculosis, a consequence of which meant that many had to be retreated. Since the implementation of the revised WHO Guidelines in 2010 almost all countries have now switched to the gold standard tuberculosis treatment regimen based on 6 months of isoniazid and rifampicin
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.
Hypertension is well known to increase the risk of stroke and other cardiovascular diseases, but up until recently few very elderly people received treatment for it. The first large randomised trial of the pharmacological treatment of hypertension in people aged 80 and over — the Hypertension in the Very Elderly Trial (HYVET) — demonstrated clear benefits of such treatment for this age group. As a direct result of HYVET, changes were made to a number of influential national and international guidelines on the treatment of hypertension, including those published by the UK's National Institute for Health and Clinical Excellence (NICE).
Research in the Oxford University Clinical Research Unit (OUCRU) in Vietnam have spent the past two decades defining effective management strategies for dengue, which is the most significant mosquito-borne viral disease in humans. Dengue affects an estimated 50 million people and kills over 22,000 patients (mainly children) worldwide each year. OUCRU research directly underpins the clinical practice guidelines worldwide for the treatment of dengue shock syndrome (DSS), including the World Health Organization's (WHO) 2009 Dengue Guidelines, leading to faster, more effective and safer resuscitation of affected individuals.