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Major Advance in Identification and Treatment of HIV-1 Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS): A Common and Serious Complication of Antiretroviral Therapy

Summary of the impact

HIV-1 tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) is an immune complication of antiretroviral therapy that has vastly increased in frequency in low- and middle-income countries over the last decade. This results from the high tuberculosis rates and the widespread availability of antiretroviral therapy. Mortality from this iatrogenic condition is estimated at 3%. Prior to our work this syndrome was poorly defined and management guidelines anecdotal. We produced the widely accepted and implemented case definition. Imperial also conducted the only randomised controlled trial to date of treatment of this condition. The results are incorporated into international guidelines.

Submitting Institution

Imperial College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

Establishment of tacrolimus as the first choice calcineurin inhibitor for the immunosuppression regimen in liver transplant recipients

Summary of the impact

Research at UCL firmly established tacrolimus as the optimal calcineurin inhibitor to use in immunosuppressive regimens following liver transplantation. Compared to ciclosporin its use improved graft survival by 6% and patient survival by 7%. Assuming 550 liver transplants per year in the UK since 2008, we can estimate that, with 90% of patients treated with tacrolimus and 10% ciclosporin, tacrolimus-based immunosuppression has resulted in 165 grafts and 192 lives being saved during the period 2008-13.

Submitting Institution

University College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Immunology

UOA01-11: Improving the Diagnosis of Tuberculosis

Summary of the impact

Developed in 2001, the University of Oxford's T-SPOT test is capable of detecting both latent and active TB infection more rapidly and accurately than the tuberculin skin test (TST). Since its commercial release in 2004, T-SPOT has been adopted by public health agencies for TB control and prevention in the US, UK and Europe. Tuberculosis (TB) is the second leading cause of death from an infectious disease, killing an estimated 1.5 million people worldwide each year. One-third of the approximately 9 million people infected with TB each year are asymptomatic, yet many go on to develop active TB if left untreated.

Submitting Institution

University of Oxford

Unit of Assessment

Clinical Medicine

Summary Impact Type

Political

Research Subject Area(s)

Medical and Health Sciences: Medical Microbiology

UOA01-16: The International Subarachnoid Aneurysm Trial: Changing Clinical Practice

Summary of the impact

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.

Submitting Institution

University of Oxford

Unit of Assessment

Clinical Medicine

Summary Impact Type

Political

Research Subject Area(s)

Engineering: Biomedical Engineering
Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences

Study A leads to changes in Tuberculosis treatment guidelines

Summary of the impact

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

Submitting Institution

University College London

Unit of Assessment

Public Health, Health Services and Primary Care

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Oncology and Carcinogenesis, Public Health and Health Services

UOA01-07: Melioidosis: Managing Chronic Infection

Summary of the impact

Sustained research by the University of Oxford's Mahidol Oxford Tropical Medicine Research Unit in Thailand (MORU) has been the driving force behind the current World Health Organization recommendations for the management of acute and chronic infection in patients with melioidosis. This research has motivated improvements in treatments and provided new strategies to identify at-risk populations, enabling clinicians to make early diagnoses. Melioidosis is a major cause of severe illness in parts of Southeast Asia and there are increasing numbers of cases in India, China, and Brazil.

Submitting Institution

University of Oxford

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Medical Microbiology

Improving Access to Tuberculosis Care for the Poor in Developing Countries

Summary of the impact

This case study describes the impact on national and global tuberculosis (TB) control policy of research led by Cuevas, Squire and Theobald at the Liverpool School of Tropical Medicine (LSTM). Early research led to the publication of the World Health Organisation (WHO) Options for National TB Control Programmes `Addressing the Poverty in TB control' in 2005. Further research led to WHO endorsement of same-day diagnosis of TB by smear microscopy (SM) in 2010. This strategy has been implemented in Malawi, Nigeria, Yemen, Ethiopia and Nepal. Alongside this we have developed and tested approaches to bring diagnosis and treatment for TB closer to the community. Same-day diagnosis and close-to-community approaches have led to improvements in access to TB care and treatment, and reductions in costs incurred during care-seeking by poor patients in these countries and elsewhere.

Submitting Institutions

University of Warwick,Liverpool School of Tropical Medicine

Unit of Assessment

Public Health, Health Services and Primary Care

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Medical Microbiology, Public Health and Health Services

The Evidence-Based Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (COPD)

Summary of the impact

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.

Submitting Institutions

University of Liverpool,Liverpool School of Tropical Medicine

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences

Extracorporeal membrane oxygenation (ECMO) in newborn babies: from pioneering technique to accepted practice

Summary of the impact

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.

Submitting Institution

University of Leicester

Unit of Assessment

Public Health, Health Services and Primary Care

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Paediatrics and Reproductive Medicine, Public Health and Health Services

20 Year Landmark Aortic Trials Produce National and International Guidelines and Alter Patient Management

Summary of the impact

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.

Submitting Institution

Imperial College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences

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