North Bristol NHS Trust

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North Bristol NHS Trust

United Kingdom
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BRISTOL, 18-Jul-2017 — /EuropaWire/ — People with Alzheimer’s disease are already helping with a ground-breaking government-funded trial led by academics from the Universities of Bristol, Cambridge, Queen’s University Belfast and University College London, and hosted by North Bristol NHS Trust, but even more people are needed to take part in the study. The research study, known as RADAR (Reducing pathology in Alzheimer’s Disease through Angiotensin taRgeting) is investigating if a drug normally used to treat high blood pressure (hypertension) has additional properties that could slow down the progression of Alzheimer’s disease (AD) in people with and without hypertension.   Approximately almost half a million people in the UK have Alzheimer’s disease, which is the most common form of dementia that affects and memory and brain function in older individuals. As part of the Prime Minister’s Challenge on Dementia, funding of nearly £2 million was awarded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership. RADAR is a multi-centre clinical trial that is investigating if losartan, a blood pressure drug that first became available in 1995, can complement current treatments for AD. The researchers believe losartan can slow down the progression of AD by improving brain blood flow and altering chemical pathways that cause brain cell damage, brain shrinkage and memory problems in AD. Recruitment for the RADAR trial, now open at 23 sites across England, Scotland and Northern Ireland, has been extended across the until the end of February 2018 and with 140 participants already taking part in the study, the researchers need another 90 people to sign up to complete the study. The RADAR study is a double-blinded placebo-controlled randomised trial, meaning that some participants will be randomly assigned to receive either the study drug, losartan, or a placebo (an identical looking pill with no active medicine) once a day for 12 months.  Nobody, including the doctors and nurses involved, will know until the study is analysed who received which. This is one of the most powerful study designs available. Initially all participants who are eligible to enrol will receive two weeks of losartan and then two weeks of the placebo to ensure they are happy taking the medication before entering the year-long trial. People with Alzheimer’s disease who have high or normal blood pressure can take part if they meet certain eligibility criteria and RADAR will use brain imaging to measure whether losartan reduces the rate of brain shrinkage normally occurs in AD.  It will also be using what are standard questionnaires on memory performance and quality of life – important indicators of whether the drug might be helpful. The trial will assess rate of whole brain shrinkage on MRI scan compared between participants on losartan and those on placebo. The researchers will also examine differences in brain blood flow, memory tests, day-to-day quality of life and changes in blood protein levels. Professor Pat Kehoe, Gestetner Professor of Translational Dementia Research at the University of Bristol, leading the trial gave an update on the study on Friday [14 July] at a symposium on Vascular Factors in Dementia and Neurodegeneration in London, hosted by the International Society of Vascular, Behavioural and Cognitive Disorders (Vas-Cog Society). Professor Kehoe said: “With an ageing population, and as we are still in search of longer acting and effective treatments, the provision for Alzheimer’s disease care will continue to increase, which will greatly impact on NHS healthcare costs and resources. “We are delighted with the confidence our funders have placed on us by agreeing to extend the study as it gives patients and their carers the opportunity to take part and help realise the potential of this UK-based trial.  The scientific case is there but we now really need people with Alzheimer’s disease to come forward and offer to take part as their involvement is essential to helping scientists find out if losartan could be a future treatment for Alzheimer’s disease. “What a lot people may not realise, even if they are seeing a doctor regularly to have their Alzheimer’s treated, because of rules around data protection and privacy unless they voice their interest to take part in research, doctors, nurses and researchers working on various trials like RADAR are not always able to contact them to invite them to take part and so many people may miss out on opportunities to participate in research that may find new treatments.” Sandra, a carer for her husband Martin who are participants of the RADAR study, said: “It was a real shock when Martin was diagnosed with Alzheimer’s disease and it has taken some time to come to terms with the diagnosis and disease. “Even though we know the study can’t help Martin, being part of the trial is important as it could help future generations.  I hope that it’s not long before a drug can be found to treat or keep Alzheimer’s disease at bay and research is important to make that happen.” If members of the public are interested in participating in the study, they can find the location and contact details of all of RADAR’s participating NHS sites on  Further information about the study can also be found here as well as a chance to contact the study team.  People can also lend their encouragement and follow the progress of the trial on Twitter @RADARTrialAD. Members of the public interested in other research opportunities in relation to Alzheimer’s disease or other forms of dementia can also register with the new Join Dementia Researchinitiative, hosted by the National Institute of Health Research (NIHR). The Join Dementia Research service allows anyone with and without dementia to sign up using basic demographic and health information and be matched to dementia research studies in their area. Research teams can then approach potential volunteers about their particular study and the volunteer can decide whether to take part on a case-by-case basis. Martin’s wife, Sandra, and his colleagues at work first noticed in 2014 that Martin had memory loss.  In April 2015, following tests and scans, Martin was diagnosed with mild cognitive impairment (MCI).  After further tests, in February 2016, doctors confirmed that Martin had posterior cortical atrophy (PCA), caused by Alzheimer’s disease. PCA, also known as Benson’s syndrome, is a rare degenerative condition in which damage occurs at the back (posterior region) of the brain. Before Martin was diagnosed he was a draughtsman and team leader for Rolls-Royce in Bristol, where he drew detailed plans of aircraft engines.  Martin’s colleagues noticed that he wasn’t checking his work properly and was doubling up on what he was writing. Martin joined Rolls Royce Bristol as an apprentice at the age of 16 and unfortunately after 43 years of service he had to take early retirement at the age of 59. Due to his Alzheimer’s disease, Martin cannot be left for very long on his own and has had to give up driving. He was told about the RADAR trial by South Gloucestershire’s memory clinic and together with his wife, Sandra, met with the RADAR team in Bristol to find out more.  They have just had their final consultation with the research team after being part of the study for 12 months. Further information on the Clinical Research Networks supporting this study can be found at: About the National Institute for Health Research (NIHR) The National Institute for Health Research (NIHR): improving the health and wealth of the nation through research. Established by the Department of Health, the NIHR: For further information, visit the NIHR website About *The Efficacy and Mechanism Evaluation (EME) The Efficacy and Mechanism Evaluation (EME) Programme supports later-phase “science-driven” clinical trials and evaluative studies, which seek to determine whether a health intervention (e.g. a drug, diagnostic technique or device) works and in some cases how or why it works.  The EME Programme is funded by the MRC and NIHR, with contributions from the CSO in Scotland, NISCHR in Wales and the HSC R&D Division, Public Health Agency in Northern Ireland. The study was funded by an MRC and NIHR partnership created to support the evaluation of interventions with potential to make a step-change in the promotion of health, treatment of disease and improvement of rehabilitation or long-term care. About the Medical Research Council The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-one MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. About North Bristol NHS Trust North Bristol NHS Trust provides hospital and community healthcare to the residents of Bristol, South Gloucestershire and North Somerset and we are also a specialist regional centre for major trauma, neurosciences, plastics and burns, orthopaedics and renal services. About Join Dementia Research Join Dementia Research is funded by the Department of Health and delivered in partnership with the National Institute for Health Research, Alzheimer’s Research UK, Alzheimer Scotland and the Alzheimer’s Society.

March 1, 2017 – CCube Solutions announces today that North Bristol NHS Trust has selected its electronic document management software (EDMS) to replace all paper case notes with an easy to use digital system providing instant access to patient medical records for 6,000 clinicians, nursing and administrative staff. The introduction of EDMS is part of the Trust’s phased Electronic Patient Record (EPR) strategy and will facilitate a more timely and extensive move towards creating a paperlite environment which also involves developing its EPR to reduce the amount of paper created on a daily basis. This will ensure that one of the largest hospitals in the UK serving people in Bristol, North Somerset and South Gloucestershire is paper free at the point of care – a key NHS England and Government goal. The new EDMS will enhance clinical effectiveness, reduce operational costs, ensure compliance with CQC guidance about records and data management, and ultimately boost patient safety and care. The choice of CCube Solutions’ EDMS will complement and augment the Lorenzo EPR solution – procured from CSC - which was implemented in November 2015. It is the first contract for CCube Solutions resulting from a new framework agreement with CSC announced in October 2016. This allows CSC to offer CCube’s EDMS to any Trust using Lorenzo who wishes to digitise and display information contained in paper medical records. Paper creates huge logistical challenges Currently North Bristol NHS Trust stores about 1.2 million medical folders off-site, with around 850 files being delivered to Southmead Hospital and other premises each day. The paperlite strategy will reduce costs and make the process more efficient. Neil Darvill, North Bristol NHS Trust’s director of informatics, says, “The business case for the EDMS project is predicated on a scan-on-demand model where only the patient notes for people booked to attend clinic will be processed, not everything in the library. This saves a huge amount of money given the other records will be destroyed in line with our retention policies and procedures as and when they reach their expiry dates.” Out of its total of 1.2 million folders, the Trust therefore estimates that it has 223,100 active patients who will need their records scanning. As each folder contains on average 150 sheets, this means 33,465,000 pages are likely to be scanned in total. The massive back scanning task will be outsourced to a scanning specialist. Darvill explains, “Our analysis shows that 70% of active patients have follow up appointments after an initial consultation. Once their records are scanned, it means for any subsequent visits, their records are available on the system for clinical staff to see.” Roll out will be staged with a paperlite project running in parallel North Bristol NHS Trust is currently piloting EDMS in two areas: lung cancer - a low volume high complexity clinic - and dermatology. This is the reverse - a high volume low complexity department. Based on lessons learnt, it will then adopt a phased approach to rolling out EDMS and scanning the records required – a process expected to take two years finishing in April 2019 given the volume of paperwork to digitize. In parallel, the Trust is working on a paperlite project to augment the investment in its EPR system. To date, PAS[1] functionality has been successfully implemented within Lorenzo with this now expanding to include real-time data capture. The Trust will customize Lorenzo to its own requirements, tailoring the system to match its own clinical pathways and ways of working. Darvill explains, “We simply can’t afford to keep generating paper at the pace we are given the number of patients we see - around 1,300 outpatient and 200 inpatient attendances each day. The purpose of the paperlite project is to look at how we capture clinical information immediately at the point of care rather than writing notes on paper and scanning them afterwards as this clearly defeats the purpose of putting in an EPR in the first place.” Until the paperlite initiative has evolved, so-called ‘day forward’ scanning will be managed in-house. During this period of transition, the Trust has purchased two production scanners from Kodak Alaris – the i4650 and i4850 – which process up to 130 and 150 pages per minute respectively. Kodak Capture Pro imaging software has also been selected which allows large batches of medical paperwork to be captured and indexed quickly and efficiently. It will then be imported into the CCube EDMS. An EDMS saves money and is simple for clinicians to use Capital expenditure on the CCube EDMS, Kodak Alaris scanners and capture software along with other implementation costs total £960,000. Over a four-year period, the Trust expects to save over £1.3 million in terms of the operational expenditure associated with the running of its paper-based processes and libraries. The cost savings come from closing the off-site facilities – expected by October 2018. Vijay Magon, CCube Solutions’ managing director, says, “EDMS in the NHS is all about transformation and presenting information contained on paper to clinicians in a much more efficient and effective way. Ease of use is crucial. Doctors have to be able to interact with the system in front of patients without it creating any unnecessary delays which could make consultations longer. Usability and effectiveness is very important which is what you get with CCube software.” About CSC Computer Sciences Corporation (NYSE: CSC) leads clients on their digital transformation journeys. The company provides innovative next-generation technology services and solutions that leverage deep industry expertise, global scale, technology independence and an extensive partner community. CSC serves leading commercial and international public sector organizations, including some of the world’s leading healthcare providers. CSC is a Fortune 500 company and ranked among the best corporate citizens. For more information, visit and About CCube Solutions CCube Solutions is an award-winning provider of enterprise content management solutions, comprising electronic document and records management, workflow, electronic forms, portal software, and systems integration. Founded in 1995, it has a proven track record working with the police, local government, NHS and in the private sector providing cost effective and scalable solutions, tailored to meet the individual requirements of customers. An AIIM Advisory Board member, CCube Solutions is active in developing and guiding the future direction of the ECM industry, and upholds AIIM’s principles of good information management, know-how applied on every customer engagement. CCube Solutions is headquartered in Milton Keynes. For further information, please visit For further information, please contact Tom Herbst Tom Herbst PR T: 07768 145571 Email:

Nye H.J.,North Bristol NHS Trust | Herrington W.G.,Churchill Hospital
Nephron - Clinical Practice | Year: 2011

Metformin is the first-line oral agent in the treatment of type 2 diabetes and has many established benefits, including the reduction of macrovascular complications of diabetes. Its prescription in patients with renal impairment is limited by concerns relating to the theoretical risk of lactic acidosis, a fear which is perpetuated by numerous case reports in which it is implicated. Critical review of this literature calls into question the validity of these claims, with metformin usually acting as an 'innocent bystander' in acutely unwell patients with conditions well recognised to precipitate lactic acidosis such as sepsis or hypovolaemia. In fact, the evidence supports the safe use of appropriate doses of metformin in patients with chronic stable renal impairment, and highlights the important possible greater risks of the alternatives, most notably severe hypoglycaemia in patients taking sulphonylureas and/or insulin and fluid retention in patients taking a thiazolidinedione. Other traditional contraindications to metformin use such as heart failure are also being re-evaluated, as the benefits of metformin in these patients are increasingly recognised. Physicians should weigh this evidence carefully before deciding to withdraw metformin therapy in their patients with stable chronic kidney disease. Copyright © 2011 S. Karger AG, Basel.

Vora A.,Sheffield Childrens Hospital | Goulden N.,Great Ormond Street Hospital | Wade R.,University of Oxford | Mitchell C.,John Radcliffe Hospital | And 4 more authors.
The Lancet Oncology | Year: 2013

Background: Minimal residual disease (MRD) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukaemia (ALL) during remission. We assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification. Methods: Between Oct 1, 2003 and June 30, 2011, consecutive children and young adults (aged 1-25 years) with ALL from the UK and Ireland were recruited. Eligible patients were categorised into clinical standard, intermediate, and high risk groups on the basis of a combination of National Cancer Institute (NCI) criteria, cytogenetics, and early response to induction therapy, which was assessed by bone marrow blast counts taken at days 8 (NCI high-risk patients) and 15 (NCI standard-risk patients) after induction began. Clinical standard-risk and intermediate-risk patients were assessed for MRD. Those classified as MRD low risk (undetectable MRD at the end of induction [day 29] or detectable MRD at day 29 that became undetectable by week 11) were randomly assigned to receive one or two delayed intensification courses. Patients had received induction, consolidation, and interim maintenance therapy before they began delayed intensification. Delayed intensification consisted of pegylated asparaginase on day 4; vincristine, dexamethasone (alternate weeks), and doxorubicin for 3 weeks; and 4 weeks of cyclophosphamide and cytarabine. Computer randomisation was done with stratification by MRD result and balancing for sex, age, and white blood cell count at diagnosis by method of minimisation. Patients, clinicians, and data analysts were not masked to treatment allocation. The primary outcome was event-free survival (EFS), which was defined as time to relapse, secondary tumour, or death. Our aim was to rule out a 7% reduction in EFS in the group given one delayed intensification course relative to that given two delayed intensification courses. Analyses were by intention to treat. This trial is registered, number ISRCTN07355119. Findings: Of 3207 patients registered in the trial overall, 521 MRD low-risk patients were randomly assigned to receive one (n=260) or two (n=261) delayed intensification courses. Median follow-up of these patients was 57 months (IQR 42-72). We recorded no significant difference in EFS between the group given one delayed intensification (94·4% at 5 years, 95% CI 91·1-97·7) and that given two delayed intensifications (95·5%, 92·8-98·2; unadjusted odds ratio 1·00, 95% CI 0·43-2·31; two-sided p=0·99). The difference in 5-year EFS between the two groups was 1·1% (95% CI -5·6 to 2·5). 11 patients (actuarial relapse at 5 years 5·6%, 95% CI 2·3-8·9) given one delayed intensification and six (2·4%, 0·2-4·6) given two delayed intensifications relapsed (p=0·23). Three patients (1·2%, 0-2·6) given two delayed intensifications died of treatment-related causes compared with none in the group given one delayed intensification (p=0·08). We recorded no significant difference between groups for serious adverse events and grade 3 or 4 toxic effects; however, the second delayed intensification course was associated with one (<1%) treatment-related death, and 74 episodes of grade 3 or 4 toxic effects in 45 patients (17%). Interpretation: Treatment reduction is feasible for children and young adults with ALL who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD by the end of induction therapy. Funding: Medical Research Council and Leukaemia and Lymphoma Research. © 2013 Elsevier Ltd.

Pontin D.,University of South Wales | Jordan N.,North Bristol NHS Trust
Palliative Medicine | Year: 2013

Background: Patients with advanced life-limiting diseases have high information needs concerning prognosis yet discussions between patients and healthcare professionals are either avoided or inaccurate due to over-optimism. Available prognostic models are problematic. Literature indicates that hospital specialist palliative care professionals are frequently asked to prognosticate, although their experience of prognostication is unknown. Identifying this experience will support the development of prognosis training for hospital specialist palliative care professionals. Aim: To explore hospital specialist palliative care professionals' experience of prognostication. Research questions: 'How do specialist palliative care team members prognosticate?'; 'How do they view prognostication?' Design: Qualitative research focus group interviews. Setting/participants: Three UK hospital specialist palliative care teams. Participants included medical doctors and palliative care nurses. Inclusion/exclusion criteria: member of hospital specialist palliative care team with knowledge and experience of prognostication. Numbers of participants: four hospital specialist palliative medicine consultants, three senior doctors in training, nine clinical nurse specialists. Results: Two major themes: Difficulties of prognostication; Benefits of prognostication. Eleven sub-themes: Difficulties (Non-malignant disease; Communicating uncertainty; Seeking definitive prognosis; Participants' feelings; Confidence in prognostication; Estimating prognosis; Dealing with reaction of prognosis; Prognostic error); Benefits (Patient informed decision-making prioritizing needs and care; Family-prioritizing commitments; Services accessing funding and services planning patient care). Conclusions: Findings highlight lack of evidence to support practice, and identify the complexity and emotional labour involved in prognostication by hospital specialist palliative care team members, and are used to discuss recommendations for further research and practice. © 2012 The Author(s).

Livingstone C.,North Bristol NHS Trust
Emergency Nurse | Year: 2013

In the UK, care for people with major injuries has improved since the introduction of trauma networks and major trauma centres, and since ambulance services began to use specific triage tools to identify major trauma. The advent of consultant-led trauma teams in emergency departments and implementation of the relevant protocols have also raised the standard of trauma care. One such protocol governs the use of tranexamic acid (TXA), which is used to control bleeding. This drug is cheap and widely available, and can save lives if administered within three hours of injury. This article reviews two recent major studies of the effects of TXA on trauma patients © 2013 RCN Publishing Ltd. All rights reserved.

Kelly M.D.,North Bristol NHS Trust
ANZ Journal of Surgery | Year: 2010

Background: Laparoscopic bile duct exploration (LBDE) is well established although the results via choledochotomy are relatively poorly documented. This report evaluates the results achieved by a single surgeon operating in one institution on an unselected group of patients using modern instrumentation. Methods: Over a 3-year period, 56 consecutive patients underwent LBDE via choledochotomy utilizing flexible choledochoscopy. Results: The median age was 61 years (range 20-90) and the mean body mass index was 29 (21-47). There were 15 patients (27%) who had emergency operations for jaundice with a mean preoperative bilirubin level of 108 umol/L (41-248). Fourteen patients (25%) had undergone failed preoperative endoscopic retrograde cholangiopancreatography. Contact electrohydraulic lithotripsy was used in 8 patients (14%) and t-tubes were inserted in 6 patients (11%) with the remainder having primary closure. There was major morbidity in 6 patients (11%) including conversion to open surgery in 1 and relaparoscopy in 3. Three patients had positive t-tube cholangiograms giving a laparoscopic clearance rate of 93% (52 patients). The median postoperative length of stay was 2.5 days (1-15). The median follow-up was 56.1 weeks (interquartile range 23.4-110.7) with no recurrent stones, strictures or late gallstone abscess. Conclusions: LBDE via choledochotomy is safe and effective but there is a definite morbidity rate. It requires significant investment in equipment, and skill with flexible endoscopy and laparoscopic suturing. © 2010 The Author. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

Vora A.,Sheffield Childrens Hospital | Goulden N.,Great Ormond Street Hospital | Mitchell C.,John Radcliffe Hospital | Hancock J.,North Bristol NHS Trust | And 4 more authors.
The Lancet Oncology | Year: 2014

Background: No randomised study has shown whether stratification of treatment by minimal residual disease (MRD) response improves outcome in children and young people with acute lymphoblastic leukaemia (ALL). We assessed whether children and young people with clinical standard and intermediate-risk ALL who have persistent MRD at the end of induction therapy benefit from augmented post-remission therapy. Methods: Between Oct 1, 2003, and June 30, 2011, we enrolled eligible patients aged 1-24 years and initially categorised them into clinical standard-risk, intermediate-risk, and high-risk groups on the basis of a combination of National Cancer Institute criteria, cytogenetics, and early morphological response to induction therapy. Clinical standard-risk and intermediate-risk patients with MRD of 0·01% or higher at day 29 of induction (MRD high risk) were randomly assigned (1:1) to standard therapy (treatment regimens A and B) or augmented post-remission therapy (regimen C). Compared with standard therapy, the augmented treatment regimen (regimen C) included an additional eight doses of pegylated asparaginase, 18 doses of vincristine, and escalated-dose intravenous methotrexate without folinic acid rescue during interim maintenance courses. Computer randomisation was used for treatment allocation and was balanced for sex, age (<10 years vs ≥10 years), and white blood cell count at diagnosis (<50 × 109/L vs ≥50 × 109/L) by minimisation. Patients, clinicians, and data analysts were not masked to treatment allocation. The primary outcomes were event-free survival and overall survival. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07355119. Findings: 533 MRD high-risk patients were randomly assigned to receive standard (n=266) or augmented (n=267) post-remission therapy. After a median follow-up of 70 months (IQR 52-91), 5-year event-free survival was better in the augmented treatment group (89·6% [95% CI 85·9-93·3]) than in the standard group (82·8% [78·1-87·5]; odds ratio [OR] 0·61 [95% CI 0·39-0·98], p=0·04). Overall survival at 5 years was numerically, but not significantly, higher in the augmented treatment group (92·9% [95% CI 89·8-96·0]) than in the standard therapy group (88·9% [85·0-92·8]; OR 0·67 [95% CI 0·38-1·17], p=0·16). More adverse events occurred in the augmented treatment group than in the standard group (asparaginase-related hypersensitivity in 18 [6·7%] in the augmented group vs two [0·8%] in the standard group and asparaginase-related pancreatitis in eight [3·0%] vs one [0·4%]; intravenous methotrexate-related mucositis in 11 [4·1%] vs three [1·1%] and methotrexate-related stomatitis in 48 [18·0%] vs 12 [4·5%]). Interpretation: Our findings suggest that children and young people with acute lymphoblastic leukaemia and 0·01% or more MRD at the end of remission induction therapy could benefit from augmented post-remission therapy. However, the asparaginase and intravenous methotrexate used in the augmented treatment regimen is associated with more adverse events than is the standard post-remission treatment regimen. Funding: Medical Research Council and Leukaemia and Lymphoma Research. © 2014 Elsevier Ltd.

Hounsome L.S.,Public Health England | Verne J.,Public Health England | McGrath J.S.,Exeter Surgical Health Services Research Unit | Gillatt D.A.,North Bristol NHS Trust
European Urology | Year: 2015

Background The Improving Outcomes in Urological Cancers guidelines recommended centralisation of cystectomy services to improve outcomes for bladder cancer (BCa) patients. Objective To investigate trends in all-cause and cause-specific survival to see if there was an improvement in survival after centralisation was implemented. To analyse trends in the number of acute hospital trusts undertaking cystectomy. Design, setting, and participants We used routine data to capture information on radical cystectomy (RC) in BCa patients aged 20 yr and older between 1998 and 2010 (n = 16 033). Outcome measurements and statistical analysis We calculated 30-d and 90-d mortality, and 30-d, 90-d, 1-yr, and 5-yr survival. The average number of RCs per trust was derived. Trends were identified using regression analysis. Results and limitations The 30-d crude mortality decreased from 5.2% to 2.1% (p < 0.001) and 90-d crude mortality decreased from 10.3% to 5.1% (p < 0.001). There was an increase in 30-d relative survival from 96% to 98% (p < 0.001), in 90-d relative survival from 91% to 96% (p < 0.001), in 1-yr relative survival from 71% to 80% (p < 0.001), and in 5-yr relative survival from 49% to 56% (2004-2006 data; p < 0.001). The mean number of RCs performed by trusts in England increased from six to 24 (p < 0.001). Smoking status and stage at diagnosis were not available. Conclusions Survival after RC has increased alongside decreases in short-term mortality. There is little evidence of a cohort effect. The trends in survival are linear and we conclude that the continued survival improvements are a result of a combination of service improvements that include service reconfiguration, improved surgical training, neoadjuvant chemotherapy, enhanced recovery principles, and continued improvements in perioperative care. Patient summary We analysed routinely collected hospital data. Outcomes for patients who undergo cystectomy have improved for all age groups. This is likely to be due to a combination of changes in practice. © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Agency: GTR | Branch: MRC | Program: | Phase: Intramural | Award Amount: 800.09K | Year: 2013

Alzheimer’s disease (AD) profoundly affects memory and brain function in older individuals. It is a slow progressive disease which can last for a number of years - a heart-breaking, exhausting and often costly reality for family and health services. With an ageing population, AD health care provision needs will significantly rise. Existing treatments only temporarily treat specific imbalances in the brain but as yet there is no cure for AD. We will undertake a clinical trial at Bristol (in collaboration with University College London (UCL)) to see if losartan, a well tolerated blood pressure drug, can complement current treatments for AD. We believe losartan will slow down the progression of AD by improving brain blood flow and altering chemical pathways that cause brain cell damage, brain shrinkage and memory problems in AD. This study will use brain imaging to measure if losartan reduces brain shrinkage which is already known to be strongly linked with reduced memory function. We will also investigate if losartan alters the profile and activity of various blood-borne proteins which may be predictive of rates of disease progression. We want to study losartan because human and animal studies tell us reduced brain blood flow is a very common and early feature in AD and contributes to memory failure. Losartan blocks a chemical pathway (angiotensin II) to improve memory problems in mice designed to have Alzheimer’s features and in people given chemicals to temporarily affect their memories. Losartan is thought to stop angiotensin II from preventing the release of vital memory chemicals in the brain. We recently found that people who have previously taken losartan, or similar drugs, have lower risk of developing AD compared to other blood pressure drugs. These drugs also slow the rate of deterioration in patients with Alzheimer’s. However clinical trials of losartan and related drugs in people with high blood pressure have shown little evidence of a reduced risk of cognitive decline or dementia in general. These studies however did not include or specifically identify AD patients and would have had many patients with mainly vascular dementia patients which have not benefited. There are no major ethical issues in this study. It may also appear costly for a small study, but it uses expensive surrogate markers of disease that can be studied in a shorter time. RADAR will offer great value for money if this cheap (3-4p per day) well tolerated drug is found to be beneficial in AD. RADAR will also provide the requisite evidence needed to justify the much larger multi-centre trial (which will use cheaper measures of disease over a longer study time) that will be needed to provide the final proof of losartan’s benefit in AD. This trial which involves leading international centres for angiotensin research in dementia (Bristol) and imaging (UCL) should provide such evidence.

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