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King's College London (KCL) research has had substantial impact, through making strong contributions to international and national guidelines which recommend that pulmonary rehabilitation should be made available to all appropriate people with COPD, including those who have had a recent hospitalisation for an acute flare-up.
Recommendations citing our research include those published internationally by a Cochrane Review and the Global Initiative for Chronic Obstructive Lung Disease, and nationally in the UK by NICE and IMPRESS — which provides clinical leadership to the NHS. These recommendations have been taken up by the NHS and are also included in NHS Best Practice Guidance (2012). The Department of Health (2010) estimated "widespread use of pulmonary rehabilitation would bring substantial annual savings".
Duchenne muscular dystrophy (DMD) is the commonest muscular dystrophy, affecting 1 in 3600 male births and 0.02% of the population. Ventilatory failure is an inevitable consequence; if untreated median survival is 20 years of age. Once a raised daytime arterial carbon dioxide level (hypercapnia) occurs, only 10% of patients survive one year. Imperial College researchers found that the introduction of non-invasive ventilation (NIV) when hypercapnia ensues extended one and five year survival to 85% and 73% respectively. Further, an Imperial-led randomised controlled trial showed NIV initiated at the time of nocturnal hypoventilation, before daytime hypercapnia, improves physiological outcomes. This management is now standard practice worldwide.
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) 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.
King's College London (KCL) researchers have had a tremendous impact on furthering the understanding of how titin mutations lead to severe hereditary and spontaneous muscle diseases, which has ultimately improved clinical guidelines, genetic diagnosis and counselling of patients and their families. New genetic tests, driven by KCL research pinpointing how specific mutations adversely impact the normal interaction of titin with other proteins and lead to a loss of muscle function, have been adopted by public health agencies across Europe. Based on these original research insights, novel potential treatment targets continue to be discovered, and drugs aimed at these targets are currently being developed.
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.
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.
Myeloproliferative neoplasms (MPN) are a group of blood disorders that affect more than 9,000 people in the UK every year. King's College London (KCL) research on the biology, diagnosis and treatment of MPN has had the following significant impacts:
In the last two decades researchers at King's College London (KCL) have revolutionized the management of benign surgical salivary disease (obstruction and tumours). Understanding the pathophysiology of the salivary glands has translated into a complete change of treatment away from traditional gland removal to minimally invasive gland preserving management. In obstructive disease >90% of stones can be released and <3% of glands removed. Similarly most parotid tumours can be removed safely by extracapsular dissection preserving the gland and significantly reducing risk of facial nerve injury. In children, >80% of childhood ranulas now can be treated without sublingual gland removal. KCL's Dental Institute has become a UK referral centre for minimally invasive salivary procedures and the procedures are now used worldwide.