Comparative safety and efficacy of vasopressors for mortality in septic shock: A network meta-analysis

© 2015, © The Intensive Care Society 2015.Introduction: Septic shock is a life-threatening condition requiring vasopressor agents to support the circulatory system. Several agents exist with choice typically guided by the specific clinical scenario. We used a network meta-analysis approach to rate the comparative efficacy and safety of vasopressors for mortality and arrhythmia incidence in septic shock patients. Methods: We performed a comprehensive electronic database search including Medline, Embase, Science Citation Index Expanded and the Cochrane database. Randomised trials investigating vasopressor agents in septic shock patients and specifically assessing 28-day mortality or arrhythmia incidence were included. A Bayesian network meta-analysis was performed using Markov chain Monte Carlo methods. Results: Thirteen trials of low to moderate risk of bias in which 3146 patients were randomised were included. There was no pairwise evidence to suggest one agent was superior over another for mortality. In the network meta-analysis, vasopressin was significantly superior to dopamine (OR 0.68 (95% CI 0.5 to 0.94)) for mortality. For arrhythmia incidence, standard pairwise meta-analyses confirmed that dopamine led to a higher incidence of arrhythmias than norepinephrine (OR 2.69 (95% CI 2.08 to 3.47)). In the network meta-analysis, there was no evidence of superiority of one agent over another. Conclusions: In this network meta-analysis, vasopressin was superior to dopamine for 28-day mortality in septic shock. Existing pairwise information supports the use of norepinephrine over dopamine. Our findings suggest that dopamine should be avoided in patients with septic shock and that other vasopressor agents should continue to be based on existing guidelines and clinical judgement of the specific presentation of the patient

Knowledge of Driving Vehicle Licensing Agency guidelines among NHS doctors:A multicentre observational study

Objectives: Over half of the UK population holds a driver's licence. The DVLA have produced guidelines to ensure drivers with medical conditions drive safely. Doctors should ensure that patients are given appropriate information and advice if they have a medical condition affecting their driving. We sought to evaluate doctors' knowledge of DVLA guidelines. Design: A 25-point questionnaire was designed from DVLA guidelines (‘The DVLA Questionnaire’). Five questions were included for each of neurology, cardiology, drug and alcohol abuse, visual, and respiratory disorders. Setting: Ealing Hospital, Northwick Park Hospital, Watford General Hospital, Norfolk and Norwich University Hospital and Leeds Teaching Hospitals Trust. Participants: 140 UK doctors. Main outcome measures: Questionnaire scores assessing knowledge of DVLA guidelines in five specialty areas. Results: The median overall questionnaire score was 28%, interquartile range 20–36% and range 0–100% [Watford 28%, Leeds 30%, Norfolk and Norwich 36%, Ealing 30%, Northwick Park 28%]. There were no significant differences between the scores for each centre (p = 0.1332), Mean scores for specialty areas were: neurology 33.1%, standard deviation 22.1; cardiology 35.6%, standard deviation 26.9; drug and alcohol abuse 30.6%, standard deviation 23.8; visual disorders 33.9%, standard deviation 23.5 and respiratory disorders 20.3%, standard deviation 24.8; overall score 30.7%. There was no significant difference between the scores of the specialty areas (p = 0.4060). Conclusions: Knowledge of DVLA guidelines in our cohort was low. There is a need for increased awareness among hospital doctors through focused education on driving restrictions for common medical conditions. Improving physician knowledge in this area may help optimise patient safety

Should the NHS be privatized? Annual varsity medical debate - London, 22nd January 2010

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract The Varsity Medical Debate, between Oxford and Cambridge Universities, brings together practitioners and the public, professors, pupils and members of the polis, to facilitate discussion about ethics and policy within healthcare. The motion on privatizing the National Health Service (NHS) was specifically chosen to reflect the growing sentiment in the UK where further discourse upon models of healthcare was required. Time and again, the outcome of British elections pivots upon the topic of financial sustainability of the NHS. Having recently celebrated its sixtieth anniversary, the NHS has become heavily politicized in recent months, especially in the aftermath of the devastating global recession.Published versio

Patient- and surgeon-adjusted control charts for monitoring performance

Objectives: To determine whether an innovative graphical tool for accurate measurement of individual surgeon performance metrics, adjusted for both surgeon-specific and patient-specific factors, significantly alters interpretation of performance data. Design: Retrospective analysis of all total knee replacements (TKRs) conducted at the host institution between 1996 and 2009. The database was randomly divided into training and testing datasets. Using multivariate generalised estimating equation regression models, the training dataset enabled generation of patient-risk and surgeon-experience adjustment factors. To simulate prospective monitoring of individual surgeon outcomes, the testing dataset was mapped on control charts. Weighted κ statistics were calculated to measure the agreement between patient-risk adjusted and fully adjusted control charts. Setting: Tertiary care academic hospital. Participants: All patients undergoing TKR at the host institution 1996–2009. Main outcome measure Operative efficiency. Results: 5313 procedures were analysed. Adjusted control charts were generated using a training dataset comprising 3756 procedures performed by 13 surgeons. The operative time gradually declined by 121 min with 25 years of experience (p<0.0001). Charts were tested by monitoring four other surgeons, performing an average of 389 procedures each. Adjustment for surgeon experience significantly altered the interpretation of operative efficiency (κ=0.29 (95% CI 0.11 to 0.47)), and enhanced assessment of a surgeon's improvement or diminishment in efficiency over time. Specifically, experience adjustment inverted the interpretation of surgeon efficiency from above average to below average, or from improving to declining performance. Conclusions: Adjustment for surgeon experience is necessary for accurate interpretation of metrics over the course of a surgeon's career. Patient-adjusted and surgeon-adjusted control charts provide an accurate method of monitoring individual operative efficiency

Trends in Mortality from Ischaemic Heart Disease and Cerebrovascular Disease in Europe: 1980-2009.

Background— Trends in cardiovascular mortality across Europe demonstrate significant geographical variation, and an understanding of these trends has a central role in global public health. Methods and Results— Ischemic heart disease and cerebrovascular disease age-standardized death rates (as per International Classification of Diseases , ninth and tenth revisions) were collated from the World Health Organization mortality database for member states of the European Union. Trends were characterized by using Joinpoint regression analysis. An overall trend for reduction in ischemic heart disease mortality was observed, most pronounced in Western Europe (&gt;60% for the Netherlands, United Kingdom, and Ireland) for both sexes from 1980 to 2009. Eastern European states, Romania, Croatia, and Slovakia, had modest mortality reductions. Most recently (2009), Lithuania had the highest mortality for males and females (318.1/100 000 and 166.1/100 000, respectively), followed by Latvia and Slovakia. France had the lowest mortality: 39.8/100 000 for males and 14.7/100 000 for females. Analysis of cerebrovascular disease mortality revealed that Austria had the largest reduction for both sexes (76.8% males, 76.5% females) from 1980 to 2009. The smallest improvement over this period was seen in Lithuania, Poland, and Cyprus (–5% to +20% approximately). France has the lowest present-day cerebrovascular disease mortality for both males and females (23.9/100 000 and 17.3/100 000, respectively). Conclusions— There is a growing disparity in cardiovascular mortality between Western and Eastern Europe, for which diverse explanations are discussed. The need for population-wide health promotion and primary prevention policies is emphasized. </jats:sec

Effects of health and social care spending constraints on mortality in England: a time trend analysis.

OBJECTIVE: Since 2010, England has experienced relative constraints in public expenditure on healthcare (PEH) and social care (PES). We sought to determine whether these constraints have affected mortality rates. METHODS: We collected data on health and social care resources and finances for England from 2001 to 2014. Time trend analyses were conducted to compare the actual mortality rates in 2011-2014 with the counterfactual rates expected based on trends before spending constraints. Fixed-effects regression analyses were conducted using annual data on PES and PEH with mortality as the outcome, with further adjustments for macroeconomic factors and resources. Analyses were stratified by age group, place of death and lower-tier local authority (n=325). Mortality rates to 2020 were projected based on recent trends. RESULTS: Spending constraints between 2010 and 2014 were associated with an estimated 45 368 (95% CI 34 530 to 56 206) higher than expected number of deaths compared with pre-2010 trends. Deaths in those aged ≥60 and in care homes accounted for the majority. PES was more strongly linked with care home and home mortality than PEH, with each £10 per capita decline in real PES associated with an increase of 5.10 (3.65-6.54) (p<0.001) care home deaths per 100 000. These associations persisted in lag analyses and after adjustment for macroeconomic factors. Furthermore, we found that changes in real PES per capita may be linked to mortality mostly via changes in nurse numbers. Projections to 2020 based on 2009-2014 trend was cumulatively linked to an estimated 152 141 (95% CI 134 597 and 169 685) additional deaths. CONCLUSIONS: Spending constraints, especially PES, are associated with a substantial mortality gap. We suggest that spending should be targeted on improving care delivered in care homes and at home; and maintaining or increasing nurse numbers

Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms

Research on iRHOM2 in the Kelsell group is funded by an MRC project grant, a MRC Clinical Fellowship (to TM) and a Cancer Research UK program grant

The Genetic and Functional Basis of Three Inherited Palmoplantar Keratodermas in Human Disease.

PhD ThesisThe ability of cells to respond to stress is fundamental for survival. The palmoplantar epidermis, by its very nature, is subjected to substantial external forces. At birth, the skin at these sites is similar to the skin elsewhere, however, as we expose it to physical stresses such as walking and gripping, it thickens to adapt. The palmoplantar keratodermas (PPKs) are a heterogeneous group of disorders characterised by abnormal thickening of the palmoplantar epidermis. Causative mutations have been identified in a diverse array of genes, such as those encoding the TNFα sheddase, ADAM17, and the water channel protein, Aquaporin 5. Three distinct PPK’s were studied in order to unravel the molecular basis of their associated diseases. The work presented here identifies the palmoplantar and stress-associated Keratin 16 as a novel interacting protein for iRHOM2, and demonstrates that this regulatory relationship contributes to palmoplantar thickness in Tylosis with Oesophageal Cancer. The deep clinical phenotyping of patients with ARVC caused by dominantly inherited mutations in desmoplakin revealed an unreported cutaneous phenotype of PPK and curly hair which may prove useful in the diagnosis of this complex disease. Finally, this Thesis includes the discovery of the first human disease-causing mutation in FAM83G, which presented with a unique phenotype of PPK and abundant curly hair and linked FAM83G to Wnt signaling. By correlating the clinical phenotype with the genotype in each case, and extrapolating from rare monogenic diseases to more common disorders, the PPK’s provide a unique resource in which to study the genetic basis of disease