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McGettigan P.,Hull York Medical School | Henry D.,Institute for Clinical Evaluative science | Henry D.,University of Toronto | Henry D.,University of Newcastle
PLoS Medicine | Year: 2011

Background: Randomised trials have highlighted the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Here, we provide estimates of the comparative risks with individual NSAIDs at typical doses in community settings. Methods and Findings: We performed a systematic review of community-based controlled observational studies. We conducted comprehensive literature searches, extracted adjusted relative risk (RR) estimates, and pooled the estimates for major cardiovascular events associated with use of individual NSAIDs, in different doses, and in populations with low and high background risks of cardiovascular events. We also compared individual drugs in pair-wise (within study) analyses, generating ratios of RRs (RRRs). Thirty case-control studies included 184,946 cardiovascular events, and 21 cohort studies described outcomes in >2.7 million exposed individuals. Of the extensively studied drugs (ten or more studies), the highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33, 1.59), and diclofenac, 1.40 (1.27, 1.55), and the lowest with ibuprofen, 1.18 (1.11, 1.25), and naproxen, 1.09 (1.02, 1.16). In a sub-set of studies, risk was elevated with low doses of rofecoxib, 1.37 (1.20, 1.57), celecoxib, 1.26 (1.09, 1.47), and diclofenac, 1.22 (1.12, 1.33), and rose in each case with higher doses. Ibuprofen risk was seen only with higher doses. Naproxen was risk-neutral at all doses. Of the less studied drugs etoricoxib, 2.05 (1.45, 2.88), etodolac, 1.55 (1.28, 1.87), and indomethacin, 1.30 (1.19, 1.41), had the highest risks. In pair-wise comparisons, etoricoxib had a higher RR than ibuprofen, RRR = 1.68 (99% CI 1.14, 2.49), and naproxen, RRR = 1.75 (1.16, 2.64); etodolac was not significantly different from naproxen and ibuprofen. Naproxen had a significantly lower risk than ibuprofen, RRR = 0.92 (0.87, 0.99). RR estimates were constant with different background risks for cardiovascular disease and rose early in the course of treatment. Conclusions: This review suggests that among widely used NSAIDs, naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk. Diclofenac in doses available without prescription elevates risk. The data for etoricoxib were sparse, but in pair-wise comparisons this drug had a significantly higher RR than naproxen or ibuprofen. Indomethacin is an older, rather toxic drug, and the evidence on cardiovascular risk casts doubt on its continued clinical use. © 2011 McGettigan, Henry.

Kilpatrick E.S.,Royal Infirmary | Rigby A.S.,University of Hull | Atkin S.L.,Hull York Medical School
Diabetes Care | Year: 2010

OBJECTIVE - Increases in blood pressure and visit-to-visit variability have both been found to independently increase the likelihood of cardiovascular events in nondiabetic individuals. This study has investigated whether each may also influence the development of microvascular complications in type 1 diabetes by examining data from the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS - Using binary longitudinal multiple logistic regression, mean systolic (SBP) and diastolic (DBP) blood pressure as well as annual visit-to-visit variability (SD.SBP and SD.DBP, respectively) was related to the risk of the development/ progression of nephropathy and retinopathy in initially normotensive subjects who did not become pregnant during the DCCT. RESULTS- Mean SBP and SD.SBP were independently predictive of albuminuria (odds ratio 1.005 [95% CI 1.002-1.008], P < 0.001 and 1.093 [1.069-1.117], P < 0.001, respectively, for 1 mmHg change), although SBP variability did not add to mean SBP in predicting retinopathy (0.999 [0.985-1.013], P = 0.93). DBP variability was also independently predictive of nephropathy (1.102 [1.068-1.137], P < 0.001) and not of retinopathy (0.991 [0.971-1.010], P = 0.37). Mean SBP was poorly related to SD.SBP (r2 < 0.01) as was mean DBP with SD. DBP (r2 < 0.01). CONCLUSIONS - Visit-to-visit variability in blood pressure consistently independently added to mean blood pressure in predicting the risk of nephropathy, but not retinopathy, in the DCCT. This observation could have implications for the management and treatment of blood pressure in patients with type 1 diabetes. © 2010 by the American Diabetes Association.

Jessney B.,Hull York Medical School
Journal of Medical Biography | Year: 2012

Joseph Lister was a remarkable British surgeon who pioneered principles of antisepsis. He died 100 years ago after devoting his life to developing and promoting safe, antiseptic surgery. In the 1800s as many as 80% of all operations resulted in infection but many people refused to accept the true nature of infection, believing instead that the deaths were coincidental. Lister became familiar with the work of Pasteur while working in Glasgow. He recognized the truth in Pasteur's work and in 1867 Lister published his landmark paper 'On the Antiseptic Principle in the Practice of Surgery' in the British Medical Journal. It proved to be a turning point in healthcare.

Redman M.G.,Hull York Medical School | Redman M.G.,Center for Reviews and Dissemination | Ward E.J.,Leeds General Infirmary | Phillips R.S.,Center for Reviews and Dissemination
Annals of Oncology | Year: 2014

Background: Probiotics are living microorganisms that are generally thought of as being beneficial to the recipient. They have been shown to be effective in people with acute infectious diarrhoea, and cost-effective in antibiotic-associated diarrhoea. Probiotics may have a role in people with cancer, as various cancer treatments often lead to diarrhoea. However, as people with cancer are often immunocompromised, it is important to assess for adverse events (AEs) such as infection, which could potentially be a consequence of deliberate ingestion of living microorganisms. Design: A systematic review was carried out to collect, analyse and synthesise all available data on the efficacy and safety of probiotics in people with cancer (PROSPERO registration: CRD42012003454). Randomised, controlled trials, identified through screening multiple databases and grey literature, were included for analysing efficacy, while all studies were included for the analysis of safety of probiotics. Primary outcomes were the reduction in duration, severity and incidence of antibiotic-associated diarrhoea and chemotherapy-associated diarrhoea, and AEs, especially probiotic-associated infection. Where possible, data were combined for meta-analysis by a random-effects model, assessing causes of heterogeneity, including differences in strains, dosage and patient characteristics. Results: Eleven studies (N = 1557 participants) were included for assessing efficacy. Results show that probiotics may reduce the severity and frequency of diarrhoea in patients with cancer and may reduce the requirement for anti-diarrhoeal medication, but more studies are needed to assess the true effect. For example comparing probiotic use to control 25 groups on effect on Common Toxicity Criteria ≥2 grade diarrhoea, odds ratio (OR) = 0.32 [95% confidence interval (CI) of 0.13-0.79; P = 0.01]. Seventeen studies (N = 1530) were included in the safety analysis. Five case reports showed probiotic-related bacteraemia/fungaemia/positive blood cultures. Conclusion(s): Probiotics may be a rare cause of sepsis. Further evidence needs to be collated to determine whether probiotics provide a significant overall benefit for people with cancer. © The Author 2014.

Datta A.,Foundation Medicine | Smith R.,Hull York Medical School | Fiorentino F.,Imperial College London | Treasure T.,University College London
Thorax | Year: 2014

Background Europe is at the peak of an epidemic of malignant pleural mesothelioma and the burden of disease is likely to continue rising in the large areas of the world where asbestos remains unregulated. Patients with mesothelioma present with thoracic symptoms and radiological changes so respiratory physicians take a leading role in diagnosis and management. Belief that the modest survival times reported after radical surgery, whether alone or as part of multimodal therapy, are longer than they it would have been without surgery relies on data from highly selected, uncontrolled, retrospectively analysed case series. The only randomised study, the Mesothelioma and Radical Surgery (MARS) trial showed no benefit. A simple modelling study of registry patients, described here, shows that an impression of longer survival is eroded when patients who were never candidates for operation on grounds of histology, performance status and age are sequentially excluded from the model. Conclusion Whenever the question arises 'Might an operation help me?' there are two responses that can and should be given. The first is that there is doubt about whether there is any survival or symptomatic benefit from surgery but we know that there is harm. The second is that there are on-going studies, including two randomised trials, which patients should be informed about. The authors suggest that the default position for clinicians should be to encourage recruitment into these trials.

Lee J.H.,Boston University | Whittington M.A.,Hull York Medical School | Kopell N.J.,Boston University
PLoS Computational Biology | Year: 2013

Cortical rhythms have been thought to play crucial roles in our cognitive abilities. Rhythmic activity in the beta frequency band, around 20 Hz, has been reported in recent studies that focused on neural correlates of attention, indicating that top-down beta rhythms, generated in higher cognitive areas and delivered to earlier sensory areas, can support attentional gain modulation. To elucidate functional roles of beta rhythms and underlying mechanisms, we built a computational model of sensory cortical areas. Our simulation results show that top-down beta rhythms can activate ascending synaptic projections from L5 to L4 and L2/3, responsible for biased competition in superficial layers. In the simulation, slow-inhibitory interneurons are shown to resonate to the 20 Hz input and modulate the activity in superficial layers in an attention-related manner. The predicted critical roles of these cells in attentional gain provide a potential mechanism by which cholinergic drive can support selective attention. © 2013 Lee et al.

Background: Multiple care failings in hospitals have led to calls for increased interprofessional training in medical education to improve multi-disciplinary teamwork. Providing practical interprofessional training has many challenges and remains uncommon in medical schools in the UK. Unlike most previous research, this evaluation of an interprofessional training placement takes a multi-faceted approach focusing not only on the impact on students, but also on clinical staff delivering the training and on outcomes for patients. Methods: We used mixed methods to examine the impact of a two-week interprofessional training placement undertaken on a medical rehabilitation ward by three cohorts of final year medical, nursing and therapy students. We determined the effects on staff, ward functioning and participating students. Impact on staff was evaluated using the Questionnaire for Psychological and Social factors at work (QPSNordic) and focus groups. Ward functioning was inferred from standard measures of care including length of stay, complaints, and adverse events. Impact on students was evaluated using the Readiness for Interprofessional Learning Survey (RIPLS) among all students plus a placement survey among medical students. Results: Between 2007 and 2010, 362 medical students and 26 nursing and therapy students completed placements working alongside the ward staff to deliver patient care. Staff identified benefits including skills recognition and expertise sharing. Ward functioning was stable. Students showed significant improvements in the RIPLS measures of Teamwork, Professional Identity and Patient-Centred Care. Despite small numbers of students from other professions, medical students' rated the placement highly. Increasing student numbers and budgetary constraints led to the cessation of the placement after three years. Conclusions: Interprofessional training placements can be delivered in a clinical setting without detriment to care and with benefits for all participants. While financial support is a necessity, it appears that having students from multiple professions is not critical for a valuable training experience; staff from different professions and students from a single profession can work successfully together. Difficulty in aligning the schedules of different student professions is commonly cited as a barrier to interprofessional training. Our experience challenges this and should encourage provision of authentic interprofessional training experience. © 2015 McGettigan and McKendree.

McKendree J.,Hull York Medical School
Clinical Teacher | Year: 2010

Background: Problem-based learning (PBL) in the UK began with the first version of Tomorrow's Doctors, published in 1993. About 12 of the 32 UK medical schools deliver PBL programmes. At a recent workshop, representatives from 10 UK medical schools, one dental school and one veterinary school discussed implementations, strengths and weaknesses of their PBL curricula.Context: The goal of the workshop was to summarise our 'warts and all' experiences of PBL. A concern expressed by the group is that when a PBL programme runs into difficulties, it is easy to blame PBL rather than what may be issues in implementation or culture. There was strong agreement that PBL performed well, works well. Conversely, PBL performed badly should not be performed at all!Innovation: The schools representatives outlined the strengths and weaknesses based on collective experience, and offered lessons and tips on how to help PBL succeed. By combining and sharing information and resources from various approaches, a picture emerged of the factors that help create a positive and effective PBL experience, and, conversely, the factors that will make it unlikely to work.Implications: Points emerging from the workshop were that strong support from senior leadership is critical, people who will not 'sign up' must not be allowed to undermine the effort, tutors should want the role rather than being co-opted, tutors should be integrated into faculty and curriculum design, induction for staff and students with ongoing tutor development is essential and, finally, personal experience shows that PBL, performed well, works well! © Blackwell Publishing Ltd 2010.

Cookson J.,Hull York Medical School
Medical Teacher | Year: 2013

Background: Not many set up a new medical school, so those that do usually do it only once. Thus most have no personal previous experience to guide them. Aim: To give those setting up a new school some broad issues to think about as they set about their task. Methods: The tips were derived from personal experience in the UK and in Africa. Results: The 12 tips identified are engage closely with the parent university from the outset; decide what the medical school is going to concentrate on first; agree on the overall aim of the school; decide who 'owns' the course; agree on the type of pedagogy to be employed; ensure good alignment between the aims, outcomes, learning framework and assessment; plan the assessment along with the rest of the course; make sure the school facilities are sufficient and appropriate to support the aims of the course; appoint the right staff; plan the research programme early; plan the co-ordination between the university and the health services at all levels; communicate, communicate, communicate. Conclusion: It is hoped that these suggestions will be widely applicable to different contexts and assist those in the exciting task of setting up a new school. © 2013 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

News Article | February 22, 2017

An innovative psychological treatment can help older people who are suffering from lower-severity depression, say researchers at the University of York -- it can also prevent more severe depression from developing An innovative psychological treatment can help older people who are suffering from lower-severity depression, say researchers at the University of York. It can also prevent more severe depression from developing. Depression is common amongst older people, with one in seven meeting the criteria for full-blown depression. Older people at the greatest risk of depression are those who suffer from loneliness and long-term illnesses, both of which affect this age group disproportionately. Being depressed can also make health problems worse and older people with depression are at an increased risk of dying. The CASPER clinical trial focussed on older people with lower-severity symptoms who are at the highest risk of becoming clinically depressed. CASPER is the largest-ever study of its kind and is reported in the Journal of the American Medical Association (JAMA). York based researchers showed that a simple and low-cost intervention reduced the symptoms of depression in older people (aged 65 and over). Those who received the intervention were also less likely to be more severely depressed after a year. Older people were also less anxious and had improved quality of life compared to people who just received care from their GP. "We developed our Collaborative Care intervention after consulting with older people and considering evidence about effective treatments for depression." said study manager, Kate Bosanquet, from the University of York's Department of Health Sciences. "We used a simple psychological approach known as behavioural activation. Older people were encouraged to re-engage with social activity and to find alternative ways of being mentally or physically active. This is important since people with depression commonly withdraw from these types of activities and this makes things worse." "Older people found Collaborative Care to be an acceptable way of accessing help,' said Della Bailey, one of the therapists working on the study. "We mostly worked with people over the telephone and found that participants appreciated this approach. This also meant that older people did not have to travel to hospital to receive psychological care." The study team, which also included researchers from the NHS, other universities and the Hull York Medical School are now planning to train NHS therapists in Collaborative Care to ensure that older people all over the UK can benefit from this intervention. "'This is the largest rigorous study of its kind and we are very grateful to the National Institute for Health Research, which funded our work, and to the hundreds of older people who participated in the study," said Chief Investigator, Professor Simon Gilbody. "'There is currently very little in the way of psychological treatment offered for older people. We hope that our research will improve the lives of older people throughout the UK."

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