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Research at the University of Nottingham has defined the clinical phenotype and management of lymphangioleiomyomatosis, a rare and often fatal multisystem disease affecting 1 in 200,000 women worldwide. The group has led the development and evaluation of new therapies and diagnostic strategies which are now part of routine clinical care. The research has underpinned the transformation of this previously under recognised and untreatable disease into a condition recognised by respiratory physicians, with international clinical guidelines, patient registries, clinical trials, specific treatments and a UK specialist clinical service.
Meningococcal disease (MCD) is a major cause of morbidity and mortality worldwide. Underpinning research by Dr Carrol and colleagues at the University of Liverpool (1997-1999), has led to improved diagnosis and case confirmation, establishing Polymerase Chain Reaction (PCR) of meningococcal DNA as a gold standard test for diagnosis. The result is better management and therefore, impact on health and welfare of patients, and on practitioners. The work was conducted in collaboration with the Meningococcal Reference Unit, which provides a national diagnosis and surveillance service. The test was recommended in NICE guidelines in 2010, thereby impacting public policy.
The University of Liverpool (UoL) research identified corticosteroid treatment for more than 3 consecutive months as a risk for serious sepsis in Crohn's disease and an indicator of poor practice; there are 115,000 Crohn's disease patients in the UK. Following this, national audits of Inflammatory Bowel Disease (IBD), also under UoL leadership, showed reduction in inappropriate long term steroid from 46% of Crohn's disease patients in 2006 to 21% in 2010. These audits led to widespread adoption of National Service Standards for the Care of Patients with IBD. Death and hospital readmission rates for IBD patients were subsequently significantly reduced.
Lung transplants represent the last hope for cystic fibrosis patients with end-stage lung disease. However, since the mid-1990s, other than in large research centres, some cystic fibrosis patients were not offered this treatment because of the variable and often poor outcome of surgery. This patient group carried a difficult to treat bacterial infection caused by the Burkholderia genus. In 2001 researchers in Newcastle published findings that demonstrated that one particular species, Burkholderia cenocepacia, was responsible for the poor outcomes and that other species of Burkholderia were not as dangerous. This finding was incorporated into international guidelines and since 2008 most transplant centres worldwide have adopted a risk stratification approach to listing patients for transplant. Consequently, more than 30 people per year worldwide now get transplants that would otherwise have been denied.
Professor Hutton's research considers the biasing effect of selection of data due to consent procedures or selective reporting, and its consequences for the validity of conclusions and reliability of results. This research has had impacts on patients directly; on health and legal professionals by informing and influencing national and international guidelines for the treatment of epilepsy used by healthcare professionals and practitioners; and has provided expert evidence to legal professionals for the conclusion of civil litigations and a General Medical Council professional misconduct trial. Hutton's research also informs ethical debate associated with the validity and robustness of study results. This work has determined guidelines for ethical conduct of research, and requirements for publications, which are significant for all biomedical researchers.
Research at the University of Liverpool (UoL) has developed and proven a straightforward diagnostic test method for bacterial blood infections. This was urgently needed as sepsis is a medical emergency that lacks adequate and rapid diagnostic tests particularly for low cost early detection. UoL's research has demonstrated that a simple optical test that can be conducted during routine testing of coagulation is an effective diagnostic, prognostic and monitoring marker for sepsis that can be routinely applied in clinical settings. There are now established UK and international laboratory standards in place. In 2010 a spinout company was formed to exploit four patents and incorporate the technology into a point-of-care device suitable for all clinical settings. The company, Sepsis Ltd, has attracted £1.45m of investment.
A new intervention has been developed and trialled in patient groups characterised by mucus obstruction of the airways. Outcomes for these patient groups have improved, and health service decisions have been informed by the underpinning research. A spin-out business, Ockham Biotech Ltd., was created and has generated overseas investment.
A novel mucolytic application and inhaled route of administration for heparin has provided a simple and cost-effective therapeutic means of relieving the symptoms of mucus obstruction in diseases including CF and COPD, which cost the NHS ~£600m and £1bn, pa, respectively.
Infection of patients with cystic fibrosis (CF) with the multidrug-resistant Nontuberculous mycobacteria (NTM), Mycobacterium abscessus, has rapidly increased over the past decade and currently affects 5-10% of CF patients worldwide. Our work has identified two possible mechanisms by which M. abscessus infection rates may be increasing: chronic azithromycin therapy may predispose individuals to infection through inhibition of autophagic-killing of mycobacteria; secondly, there is frequent person-to-person transmission of M. abscessus despite conventional infection control measures. This research has had a direct impact on how CF is treated, and has influenced infection control guidelines throughout the UK.
The Leicester Cilia Group (LCG) established methods to study ciliary damage and dysfunction, transforming the diagnosis and management of Primary Ciliary Dyskinesia (PCD), a genetic disorder that causes severe permanent lung damage in children. The group developed diagnostic methods, adopted in the UK and internationally, that increased the accuracy and speed of diagnosis, uncovering a number of previously unrecognised phenotypes. The group was instrumental in the establishment of the first nationally funded diagnostic service (three centres, including Leicester) in the world. This has resulted in the group jointly leading a successful bid (2012) to set up the first nationally funded management service for children with PCD.
Research from the University of Nottingham on aminoglycoside antibiotics in cystic fibrosis (CF) has changed clinical practice and improved patient safety internationally. There are over 70,000 people with CF worldwide. Most require frequent and prolonged intravenous courses of aminoglycoside antibiotics (which can cause kidney damage) to treat chronic lung infection with Pseudomonas aeruginosa. This infection may lead to respiratory failure and death. Our research has influenced national and international guidelines, and changed practice, such that once-daily aminoglycosides (less toxic to the kidneys) are now used. We have also stopped the use of gentamicin, in favour of less toxic aminoglycosides.