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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.
Our early work on large animal models underpinned trials undertaken by ourselves and by others, which in turn have resulted in therapeutic hypothermia becoming standard care for infants with moderate to severe neonatal encephalopathy. In 2010 this was recommended in NICE guidance. Over 3,000 babies have now been given this treatment, and we estimate that 450 have avoided death or serious neurological disability. The estimated economic value of this is over £125 million.
As a consequence of a research-based training programme developed at the University of Bristol, the rates of perinatal hypoxia and intrapartum fetal injury in Bristol and two pilot units in Australia and the US are now among the lowest in the world. The improvements achieved in Bristol, the US and Australia have also been successfully achieved in a low resource setting in Zimbabwe.
In response to demand from maternity units across the world, the Bristol team has developed PROMPT — a PRactical Obstetric Multi-Professional Training package, which has been successfully implemented in over 20 countries worldwide. PROMPT has had a major health and welfare impact on more than a million mothers and their babies, as well as bringing substantial economic benefits and supporting international development.
Researchers at the University of Bristol have developed tests to track low-level leukaemia — `minimal residual disease' (MRD) — in children with acute lymphoblastic leukaemia (ALL) down to levels thousands of times lower than detectable by light microscopy. These tests have become the gold standard for monitoring of leukaemic response in clinical trials. MRD testing has been shown in 2013 to allow safe de-intensification of treatment for one-fifth of patients treated nationally, with substantial savings in toxicity and treatment-related expense. The same techniques have also improved worldwide understanding of how disease clearance is related to success after haemopoietic stem cell transplantation.
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.
Research conducted at the University of Bristol has influenced the direction of research and investment of pharmaceutical companies and led to improved patient outcomes in preliminary clinical trials. Myocardial infarction (heart attack) and stroke are a major health issue for Western society and a frequent cause of premature death. Treatment of these conditions involves procedures that restore blood flow to the tissues, but there is a significant risk of further tissue damage when the blood supply returns — known as reperfusion injury — due to inflammation and oxidative stress. Since 1993, Professor Halestrap has conducted pioneering work on the role of the mitochondrial permeability transition pore (MPTP) in reperfusion injury. In 1995, he demonstrated that inhibition of the MPTP protects the rat heart from reperfusion injury and in 1998, with his collaborators he demonstrated protection in rat brains. His studies helped establish the MPTP as the most promising target for developing drugs against reperfusion injury. In 2000, pharmaceutical companies started investing in the research and development of such drugs. Subsequently, this has led to formal contracts with seven pharmaceutical companies, a patent and seven clinical trials with improved outcomes for patients in an initial Phase II trial leading to a large ongoing multi-centre Phase III trial.
By identifying a novel approach to treat allergy and autoimmune disease the University of Bristol has created a new field of research into antigen-specific peptide immunotherapy. Initial work carried out by Professor David Wraith at the University has since 2008 led to the creation of new businesses, (including the spinout company Apitope), generated 100s of millions of pounds of investment and underpinned both the adoption of new technology and the development of new products by the pharmaceutical industry. The commercial impact of this research into antigen specific immunotherapy is on-going and expanding.
Research conducted at the University of Bristol between 2002 and 2006 directly influenced a significant commercial decision about use of a food additive to aid appetite control, which protected consumers from an ineffective product. Concerns about increasing levels of obesity worldwide and the toll this takes not only on human health but on health care costs, have led to the development of food ingredients that satisfy hunger for longer (enhance satiety). One such major new ingredient, Fabuless, which is owned by DSM (Dutch State Mines), a leading global manufacturer of food ingredients, was being considered by Unilever for inclusion in its range of diet foods. DSM and Unilever contacted Professor Peter Rogers, who is known for his novel methods for the experimental study of appetite control, to test the effectiveness of Fabuless. Rogers demonstrated no satiety effect of Fabuless when consumed in realistic products, which caused Unilever to abandon Fabuless as a potential food ingredient in 2009. Publication of the research also meant that other food manufacturing companies and regulatory authorities were informed about the ineffectiveness of Fabuless.
Novel methods of measurement developed by Marek Czosnyka, Peter Hutchinson, David Menon and John Pickard have provided new insights into the pathophysiology of brain injury, led to commercial applications, and influenced patient care in terms of improved outcome for clinical trials. Multimodality brain monitoring of intracranial pressure (ICP), brain oxygen and microdialysis; PET/MRI imaging of critically ill patients; and computerised CSF infusion tests for shunt function in hydrocephalus have each impacted on the clinical practice and the ability to evaluate novel treatments and interventions in brain injury. This work has led directly to the establishment of a National Institute for Health Research (NIHR) Health Technology Cooperative for Brain Injury.
Research by a team at Southampton into amyloid beta protein (A03b2) immunisation to treat Alzheimer's disease has been key to changing the way the global medical community understands and reacts to the disease. The first to observe that A03b2 immunisation clears A03b2 plaques, the team's studies were pivotal in initiating and informing the safe clinical trial development of 40 immunotherapy agents; investments of $3bn by the pharmaceutical industry; and 30 phase II and phase III studies. The research shaped US government policy on new safety measures for clinical trials and played a leading role in the doubling of UK funding to tackle Alzheimer's.