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Research in the Centre of Evidence Based Dermatology at the University of Nottingham has improved the lives of children with eczema throughout the world. This has been achieved by improving the evidence base for clinical care through identifying treatments that work and those that do not, thus reducing the burden of disease for patients and reducing costs for patients and the NHS. Clinical care has been improved, economic benefits have been realised and Government policy informed.
Our research has shown that water softeners are not effective in reducing the symptoms of moderate to severe eczema in children, and that their use provides no additional benefit over usual care. This finding has had an impact on Healthcare practitioners ensuring they are now able to offer the evidence-based advice to patients that the use of water softeners will not alleviate the symptoms of eczema. This advice not only eliminates false hope in patient groups but also results in significant cost savings for families of children with moderate to severe eczema who might otherwise have purchased water softeners.
Psoriatic arthritis (PsA) is a chronic inflammatory disease of joints, skin and tendons that affects 0.5-0.8% of the population worldwide. PsA can cause substantial psychological and social problems and also causes increased risk of death from cardiovascular disease. Research conducted by Prof Iain McInnes at the University of Glasgow in partnership with leading pharmaceutical company, Janssen, has provided robust evidence of the clinical benefits and safety of the cytokine blocker ustekinumab, leading to its approval for use for PsA by the European Medicines Agency in July 2013. This was the first approval of a PsA drug with a new mode of action in a decade, providing a novel treatment for approximately 1.25 million PsA patients across Europe.
Dementia is one of the greatest problems facing society today, both in financial terms and in terms of the quality of life of patients and caregivers. Newcastle research identified that cholinesterase inhibitors (CHEIs), originally licenced for use in Alzheimer's disease, would be of greater benefit in two other types of dementia; Lewy body dementia and Parkinson's disease. CHEIs are now recommended in national and international guidelines as a treatment for the cognitive and psychiatric symptoms associated with both of these conditions, which previously had no effective treatment. CHEIs are also licenced worldwide for use in Parkinson's dementia, and are used off- licence across the world as a first-line treatment for dementia with Lewy bodies.
Research investigating genetic and environmental interactions leading to skin barrier breakdown in atopic eczema has delivered health benefits by improving the prevention and treatment of this condition. We found that established emollient formulations (e.g. Aqueous Cream BP) containing the harsh emulsifier sodium lauryl sulphate (SLS) damage the skin barrier in patients with atopic eczema and identified an underlying molecular mechanism. Consequently, the NICE Quality Standard and Guidelines now reflect our advice that Aqueous Cream should not be used as a leave-on emollient, SLS has been removed from all emollient formulations in the UK and we have helped develop the next generation of `SLS-free' skin-care products. Medicines regulators including the Medicines and Healthcare products Regulatory Agency (MHRA) and New Zealand MedSafe have also issued new advice as a result of our research.
Malignant pleural mesothelioma (MPM) is a treatable but incurable cancer that originates in the cells lining the lungs. Over 14,000 people worldwide are diagnosed annually with MPM. Antifolates are often used in cancer therapy, but side effects are a major issue. A retrospective analysis of cancer trials and phase 1 trial of MPM patients, carried out by Newcastle in collaboration with Eli Lilly Pharmaceuticals, determined that plasma homocysteine levels were a good predictor of drug toxicity in cancer patients treated with the antifolate pemetrexed, and that this drug was well tolerated by patients with low homocysteine levels. It was also determined that pemetrexed treatment should be supplemented with vitamin B12 as well as folic acid, to reduce drug toxicity. Ultimately, this permitted the continued development of pemetrexed, which otherwise would have been too toxic for clinical use. It is now the only licensed drug for MPM treatment in combination with platinum-based chemotherapy.
Research on Congenital Adrenal Hyperplasia (CAH) at the University of Sheffield has resulted in both health and commercial impacts. The research has led to a new drug treatment, Chronocort®, being developed for CAH. Chronocort® has been tested in CAH patients with the positive outcome of improved disease control.
Commercial impact arose from the creation of a spin-out company, Diurnal Ltd, in 2004 which has raised investment of £3.8M since 2008, including £0.4M from pharmaceutical industry sources, and (as an SME partner) a €5.6M Framework 7 grant to develop a paediatric treatment for CAH. Diurnal has created five new jobs and has contracts with six UK companies worth £2.7M.
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.
Research conducted by Professor Tim Goodship and co-workers at Newcastle has had a profound effect on the prognosis for patients with atypical haemolytic uraemic syndrome (aHUS). By engaging in research on the genetic factors underlying the disease they developed an understanding of the molecular mechanisms responsible. Identifying that the majority of patients with aHUS have either acquired or inherited abnormalities of the regulation of complement (part of the immune system) led to the establishment of a UK national service for genetic screening and treatment with the complement inhibitor eculizumab. As eculizumab is now available to patients in England, the progression to end-stage renal failure can be prevented and patients already on dialysis will soon be successfully transplanted.
Atopic eczema and associated conditions — asthma, food allergy and hay fever — affect ~40% of the population in developed nations. They cause significant morbidity and create a multibillion-pound global healthcare burden. The discovery that loss-of-function mutations in the gene encoding filaggrin represent a strong risk factor for eczema, asthma and peanut allergy has defined a key pathological mechanism in atopic disease. This breakthrough in understanding has brought new focus on the skin barrier. It has shown impact in treatment approaches to maintain barrier function, translational research targeting epithelial dysfunction and improved public and professional awareness of the role of skin in atopic disease.