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We established a comprehensive international collaboration to develop, validate and apply new scales for the identification and quantification of non-motor symptoms and signs in Parkinson's disease (PD). This was intended to provide tools to assess response to treatment, help define the clinical prodrome of PD and provide a means to evaluate novel therapies designed to modify the course of disease. The scales have been produced, validated and published. They have been incorporated as end points in international clinical trials for PD and have been introduced by specialist societies and NHS commissioners as a standard of care for PD patients.
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.
King's College London (KCL) researchers were the first to identify that an early sign of diabetic kidney disease was the presence of albumin in the urine, a condition known as albuminuria. Building on this finding, the KCL Unit of Metabolic Medicine designed and led in-house, national then international randomised controlled clinical trials with the aim of preserving kidney function in diabetic patients. Ultimately, KCL research established that several drug inhibitors of the renin-angiotensin-aldosterone system (RAAS) can control albuminuria, slow the deterioration of kidney function and significantly extend survival rates in diabetic patients. These drugs are now generically available, and their prescription is recommended by current international clinical guidelines across North America, Europe, Australia and Asia. This shows major impact in terms of reach and significance.
Bio-inspired computer algorithms, developed by Dr Stephen Smith at the University of York, have been integrated with commercially available hardware that analyse patients' movements to diagnose and monitor a range of neurodegenerative conditions including Parkinson's disease and Alzheimer's disease. Clinical studies undertaken in the UK and USA report a diagnostic accuracy exceeding 90% - a 15% improvement on current clinical practice. A new spinout company, ClearSky Medical Diagnostics Ltd, has licenced four products exploiting this technology to nine health centres in the UK, USA, Singapore, Australia and UAE, transforming clinical testing with improved diagnosis and monitoring of patients in hospitals and their own homes.
Acute promyelocytic leukaemia (APL) is of interest because it is the first cancer that can be cured with drugs that target a unique molecular abnormality. KCL research has developed accurate molecular techniques which are essential to diagnose the disease, guide treatment, and monitor for relapse. Sub-microscopic levels of leukaemic cells remaining in the patient's bone marrow after treatment (referred to as `minimal residual disease') give an early warning of re-occurrence of the disease. Our laboratory has developed sensitive tests for these cells, allowing treatment to be tailored to individual patient needs. This has had a major impact on APL diagnosis and monitoring and has been incorporated in national and international disease-treatment guidelines.
Motor neuron disease (MND) is a devastating and debilitating disease with poor prognosis; most patients die from progressive respiratory failure within three years of onset. A randomised controlled trial conducted in Newcastle provided robust evidence that non-invasive ventilation for patients with MND can significantly improve quality of life and increase survival (216 days with non-invasive ventilation compared to 11 days without). Findings from this trial underpinned recommendations concerning the use of non-invasive ventilation in MND in clinical guidelines internationally, and use in clinical practice has increased in the UK, across Europe, and in the US and Australasia. In the UK, the number of MND patients successfully established on non-invasive ventilation in 2009 had increased 3.4-fold since 2000 and since 2009 has further increased almost two-fold.
King's College London (KCL) researchers contributed to the discovery that increased C fibre nerve activity in the bladder is a major cause of overactive bladder (OAB) syndrome. Based on this insight, KCL researcher Professor Dasgupta, a surgical urologist at Guy's Hospital, and his team pioneered a new surgical technique for micro-injecting Botulinum Toxin-A (BTX-A) directly into the bladder to suppress C fibres and improve bladder control. The KCL team then conducted the world's first successful clinical trials into the minimally invasive injection of BTX-A n OAB patients. These trials received significant international media coverage. This cost-effective OAB therapy is now licensed by the EU and FDA, is recommended in national and international guidelines, and has significantly improved the treatment of a common health problem.
King's College London (KCL) research has made a major contribution to improving the quality of life for patients who have anaemia linked with chronic kidney disease. Studies undertaken by KCL researchers established that intravenous iron supplementation was required in anaemic patients with advanced kidney disease, in whom oral iron therapy was ineffective, and defined the best regimes for administration of intravenous iron. Subsequent KCL work on drugs that stimulate production of red blood cells (erythropoiesis) defined the target levels of haemoglobin to aim for in chronic kidney disease patients. Most recently, KCL researchers made the key discovery that the novel drug peginesatide for the first time enables the rescue of patients who develop a rare and potentially fatal reaction against erythropoietin (which is the commonest treatment for anaemia in chronic kidney disease). These KCL research studies have had a significant impact by making a major contribution to national and international clinical guidelines, including UK NICE guidelines and the 2012 National Kidney Foundation KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease.
Research into the genetic causes of Parkinson's disease by Professor Nick Wood's group at the UCL Department of Molecular Neuroscience, describing the mutations in the gene LRRK2, have led to the development of a new genetic test which is now available to patients and their families. This benefits them by providing a precise diagnosis, and an understanding of the risk of disease to relatives. The research has provided new insight into patterns of Parkinson's disease in particular ethnic groups, and given rise to improved public understanding and high profile philanthropy. This discovery has also opened up a new area of research into disease-modifying treatments in Parkinson's disease within the pharmaceutical industry, leading to new drug candidates.
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease that is subject to relapses (flares) and remissions. Measuring disease activity in multiple systems, some of which may be worsening while others are improving, is a challenge in the management of patients with SLE and also in the conduct of clinical trials of new drugs for the treatment of SLE. The British Isles Lupus Assessment Group (BILAG) disease activity index for measuring lupus was developed by Professors Paul Bacon and Caroline Gordon at the University of Birmingham and has been validated and implemented for clinical trials and routine clinical practice. The instrument is able to capture significant improvement or worsening in lupus disease activity on a system based approach, leading to improved management and treatment of patients. It is the preferred disease activity instrument for international SLE trials recommended by the US Food and Drug Administration and European Medicines Agency, demonstrating impact on health and welfare and public policy and health services.