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Collaboration between Professor Alison Brading at the University of Oxford and her clinical colleague, Professor Neil Mortensen, translated her pioneering research on the ability of nitric oxide to act as a neurotransmitter in smooth muscle into a new treatment for the common, painful, condition of anal fissure. For many years the principal treatment was elective surgery, which carries a risk of faecal incontinence. Nitric oxide donors are now used routinely to limit and resolve the development of anal fissure, improving the lifestyle of sufferers and reducing the economic costs associated with time off work and surgical intervention. The treatment has been in existence since 2000, but since 2008 it has repeatedly been confirmed as the most effective non-surgical intervention.
Postoperative local recurrence affects 20-30% of patients with rectal cancer. Between 1993 and 2013, University of Leeds researchers identified the importance of pathology studies to show a disease-free margin around the excised tumour and how to predict this margin routinely and accurately using simple histopathology and preoperative MRI.
We also used photography in the pathological assessment of the quality of surgery and were instrumental in the adoption of modern techniques by professional organisations around the world.
Following adoption of our techniques in England and Scotland, local recurrence has halved with 10% better survival and cost savings of £60 million. Our methods have also become the gold standard in the treatment of rectal cancer patients around the world.
University of Bristol researchers at the Bristol Heart Institute (BHI) have pioneered the development and clinical take-up of the novel technique of off-pump coronary artery bypass (OPCAB) surgery. Over ten clinical trials and several large cohort analyses have assessed the impact of this technique on elective and high-risk patients. The results have shown that it is as safe as the conventional coronary artery bypass grafting (CABG) technique that uses a cardiopulmonary bypass pump and cardioplegic arrest. Most importantly, however, OPCAB significantly reduces the risk of post-operative complications, and reduces morbidity and mortality. It also uses less hospital resources, reducing time in intensive care and length of hospital stay. In 2011 (the last year for which data are available), 20% of CABG operations in the UK were carried out with the OPCAB technique and it has had significant take-up overseas (for example, 18% of CABG operations in the US and 21% in the EU in 2010). NICE has recommended the safety and efficacy of OPCAB surgery.
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.
Imperial College preclinical studies guided the desired selectivity profile for long-acting muscarinic receptor antagonists (LAMA). Binding, functional and clinical studies from Imperial laboratories were the first to demonstrate the long duration of tiotropium bromide (Spiriva®) in human tissue, and confirmed its long duration of action in patients and established it as the first-line treatment for chronic obstructive pulmonary disease (COPD). Tiotropium has had a beneficial impact on the management of COPD and is incorporated into the major international treatment guidelines. It improves symptoms, reduces exacerbations and mortality, and provides a cost-effective therapy. Imperial have also produced the first pre-clinical and clinical data for the next LAMA in development (glycopyrrolate, Seebri®), which has recently been marketed. Our profiling of tiotropium has also led to the development of several novel LAMA.
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.
The MRC Conventional versus Laparoscopic-Assisted Surgery In Colorectal Cancer trial (CLASICC) is the largest and most successful UK trial of a technology applied to general surgery. It addressed an area of huge clinical uncertainty, providing a rigorous evaluation of a new technology and enabling its safe and widespread implementation. The impact of CLASICC has been global, confirming the advantages for patients (quicker recovery) and healthcare providers (cost-effectiveness) and so influencing national and international policy in favour of the laparoscopic technique. It informed NICE guidance and led to a major DH initiative that has seen the UK become one of the largest providers in the world of laparoscopic colorectal cancer surgery. CLASICC is regarded as a benchmark surgical trial, combining high quality trial design with rigorous quality assurance, which has informed the design of many subsequent colorectal cancer studies.
An artificial cervical joint, designed by Mr Steven Gill, honorary Chair in the University of Bristol and consultant in Neurosurgery at Frenchay Hospital, is widely used for the treatment of degenerative cervical disc disease. Patients who have received the device have retained neck mobility and have experienced less neck pain and better neurological function than patients who have undergone conventional treatment involving fusion of the vertebrae. The device has also yielded substantial long-term savings as far fewer patients require secondary surgery. Gill's device was the first artificial cervical joint approved by the US Food and Drug Administration (FDA), in 2007. In early 2008, the global medical technology company Medtronic launched the device commercially in the US. The device is now used in 60 countries and has so far generated more than $137 million in sales.
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.
Research at Hull into hypersensitivity of the airways has provided novel insights into the epidemiology and causes of cough, and its burden on patients. This was achieved by the development of novel methodologies that allow the rigorous and objective testing of new and existing drugs. Patients benefit through the online provision of a diagnostic tool, and Proctor & Gamble have successfully exploited the cloned cell receptors in their drug development programme resulting in a new range of pharmaceuticals for cough. The work has underpinned the standardisation of cough challenge methodology through incorporation in national and international healthcare guidelines leading to a widespread improvement in patient treatment.