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Background: Since the mid-1990s, excess mortality has increased markedly for adults aged 25-44 years in the north compared with the south of England. We examined the underlying causes of this excess mortality and the contribution of socioeconomic deprivation., Methods: Mortality data from the Office of National Statistics for adults aged 25-44 years were aggregated and compared between England's five most northern versus five most southern government office regions between Jan 1, 1981, and Dec 31, 2016. Poisson regression models, adjusted for age and sex, were used to quantify excess mortality in the north compared with the south by underlying cause of death (accidents, alcohol related, cardiovascular disease and diabetes, drug related, suicide, cancer, and other causes). The role of socioeconomic deprivation, as measured by the 2015 Index of Multiple Deprivation, in explaining the excess and regional variability was also explored., Findings: A mortality divide between the north and south appeared in the mid-1990s and rapidly expanded thereafter for deaths attributed to accidents, alcohol misuse, and drug misuse. In the 2014-16 period, the northern excess was incidence rate ratio (IRR) 1·47 (95% CI 1·39-1·54) for cardiovascular reasons, 2·09 (1·94-2·25) for alcohol misuse, and 1·60 (1·51-1·70) for drug misuse, across both men and women aged 25-44 years. National mortality rates for cardiovascular deaths declined over the study period but a longstanding gap between north and south persisted (from 33·3 [95% CI 31·8-34·8] in 1981 to 15·0 [14·0-15·9] in 2016 in the north vs from 23·5 [22·3-24·8] to 9·9 [9·2-10·5] in the south). Between 2014 and 2016, estimated excess numbers of death in the north versus the south for those aged 25-44 years were 1881 (95% CI 726-2627) for women and 3530 (2216-4511) for men. Socioeconomic deprivation explained up to two-thirds of the excess mortality in the north (IRR for northern effect reduced from 1·15 [95% CI 1·14-1·15; unadjusted] to 1·05 [1·04-1·05; adjusted for Index of Multiple Deprivation]). By 2016, in addition to the persistent north-south gap, mortality rates in London were lower than in all other regions, with IRRs ranging from IRR 1·13 (95% CI 1·12-1·15) for the East England to 1·22 (1·20-1·24) for the North East, even after adjusting for deprivation., Interpretation: Sharp relative rises in deaths from cardiovascular reasons, alcohol misuse and drug misuse in the north compared with the south seem to have created new health divisions between England's regions. This gap might be due to exacerbation of existing social and health inequalities that have been experienced for many years. These divisions might suggest increasing psychological distress, despair, and risk taking among young and middle-aged adults, particularly outside of London., Funding: Medical Research Council and Wellcome Trust., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The performance of emerging transcatheter aortic valve implantation (TAVI) clinical prediction models (CPMs) in national TAVI cohorts distinct from those where they have been derived is unknown. This study aimed to investigate the performance of the German Aortic Valve, FRANCE-2, OBSERVANT and American College of Cardiology (ACC) TAVI CPMs compared with the performance of historic cardiac CPMs such as the EuroSCORE and STS-PROM, in a large national TAVI registry., Methods: The calibration and discrimination of each CPM were analyzed in 6676 patients from the UK TAVI registry, as a whole cohort and across several subgroups. Strata included gender, diabetes status, access route, and valve type. Furthermore, the amount of agreement in risk classification between each of the considered CPMs was analyzed at an individual patient level., Results: The observed 30-day mortality rate was 5.4%. In the whole cohort, the majority of CPMs over-estimated the risk of 30-day mortality, although the mean ACC score (5.2%) approximately matched the observed mortality rate. The areas under ROC curve were between 0.57 for OBSERVANT and 0.64 for ACC. Risk classification agreement was low across all models, with Fleiss's kappa values between 0.17 and 0.50., Conclusions: Although the FRANCE-2 and ACC models outperformed all other CPMs, the performance of current TAVI-CPMs was low when applied to an independent cohort of TAVI patients. Hence, TAVI specific CPMs need to be derived outside populations previously used for model derivation, either by adapting existing CPMs or developing new risk scores in large national registries., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We aim to determine the prevalence of anemia in acute coronary syndrome (ACS) patients and compare their clinical characteristics, management, and clinical outcomes to those without anemia in an unselected national ACS cohort., Methods and Results: The Myocardial Ischemia National Audit Project (MINAP) registry collects data on all adults admitted to hospital trusts in England and Wales with diagnosis of an ACS. We conducted a retrospective cohort study by analyzing patients in this registry between January 2006 and December 2010 and followed them up until August 2011. Multiple logistic regressions were used to determine factors associated with anemia and the adjusted odds of 30-day mortality with 1 g/dL incremental hemoglobin increase and the 30-day and 1-year mortality for anemic compared to nonanemic groups. Analyses were adjusted for covariates. Our analysis of 422 855 patients with ACS showed that 27.7% of patients presenting with ACS are anemic and that these patients are older, have a greater prevalence of renal disease, peripheral vascular disease, diabetes mellitus, and previous acute myocardial infarction, and are less likely to receive evidence-based therapies shown to improve clinical outcomes. Finally, our analysis suggests that anemia is independently associated with 30-day (OR 1.28, 95% CI 1.22-1.35) and 1-year mortality (OR 1.31, 95% CI 1.27-1.35), and we observed a reverse J-shaped relationship between hemoglobin levels and mortality outcomes., Conclusions: The prevalence of anemia in a contemporary national ACS cohort is clinically significant. Patients with anemia are older and multimorbid and less likely to receive evidence-based therapies shown to improve clinical outcomes, with the presence of anemia independently associated with mortality outcomes., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Multimorbidity is common among older people and presents a major challenge to health systems worldwide. Metrics of multimorbidity are, however, crude: focusing on measuring comorbid conditions at single time-points rather than reflecting the longitudinal and additive nature of chronic conditions. In this paper, we explore longitudinal comorbidity metrics and their value in predicting mortality.Using linked primary and secondary care data, we conducted a retrospective cohort study on adults in Salford, UK from 2005 to 2014 (n = 287,459). We measured multimorbidity with the Charlson Comorbidity Index (CCI) and quantified its changes in various time windows. We used survival models to assess the relationship between CCI changes and mortality, controlling for gender, age, baseline CCI, and time-dependent CCI. Goodness-of-fit was assessed with the Akaike Information Criterion and discrimination with the c-statistic.Overall, 15.9% patients experienced a change in CCI after 10 years, with a mortality rate of 19.8%. The model that included gender and time-dependent age, CCI, and CCI change across consecutive time windows had the best fit to the data but equivalent discrimination to the other time-dependent models. The absolute CCI score gave a constant hazard ratio (HR) of around 1.3 per unit increase, while CCI change afforded greater prognostic impact, particularly when it occurred in shorter time windows (maximum HR value for the 3-month time window, with 1.63 and 95% confidence interval 1.59-1.66).Change over time in comorbidity is an important but overlooked predictor of mortality, which should be considered in research and care quality management., Competing Interests: The authors have no conflicts of interest to disclose.

Background: "Obesity paradox" refers to an association between obesity and reduced mortality (contrary to an expected increased mortality). A common explanation is collider stratification bias: unmeasured confounding induced by selection bias. Here, we test this supposition through a realistic generative model., Methods: We quantify the collider stratification bias in a selected population using counterfactual causal analysis. We illustrate the bias for a range of scenarios, describing associations between exposure (obesity), outcome (mortality), mediator (in this example, diabetes) and an unmeasured confounder., Results: Collider stratification leads to biased estimation of the causal effect of exposure on outcome. However, the bias is small relative to the causal relationships between the variables., Conclusions: Collider bias can be a partial explanation of the obesity paradox, but unlikely to be the main explanation for a reverse direction of an association to a true causal relationship. Alternative explanations of the obesity paradox should be explored. See Video Abstract at http://links.lww.com/EDE/B51.

Aims: We evaluated the relationship between body mass index (BMI) and cancer mortality in incident type 2 diabetes. Methods: We used the Clinical Practice Research Datalink GOLD (1998‐2015), linked with the Office of National Statistics mortalities, and derived an incident type 2 diabetes cohort (N = 176 886; aged 30‐85 years). We determined BMI ±12 months diabetes diagnosis. The primary outcome was cancer mortality, categorized into deaths from obesity‐related cancers (ORCs) and non‐ORCs. Secondary outcomes were site‐specific cancer mortality and main causes of deaths [cancer, cardiovascular disease (CVD), non‐cancer non‐CVD]. We developed gender‐specific Cox models and expressed risk as hazard ratios and 95% confidence intervals, stratified by smoking status. Results: With 886 850 person‐years follow‐up, 7593 cancer deaths occurred. Among women who never smoked, there were positive associations between BMI and deaths from endometrial (hazard ratios per 5 kg/m2: 1.43; 95% confidence interval 1.26‐1.61). Among men, associations between BMI and ORC mortality were inverse but attenuated towards null among never smokers and excluding deaths in the first 2 years. In men, the proportion of CVD deaths increased from 36.8% in BMI category 22.5 to 24.9 kg/m2 to 43.6% in BMI category ≥40 kg/m2 (p <.001). Conclusions: We found some relationships between BMI and cancer mortality in patients with type 2 diabetes, but interpretations need to account for smoking status, reverse causality and deaths from CVD. [ABSTRACT FROM AUTHOR]

Life-space mobility (LSM) is a holistic measure of resilience to physical decline and social isolation in later life. To promote its use as an outcome in geriatric studies and in clinical practice, this review paper explains the concept of LSM; outlines available questionnaires for LSM assessment, provides an overview of associations between LSM and other outcomes, and discusses emerging methods to measure LSM using wearable sensors. Based on performed activity around a central geographical anchor, LSM aims to quantify the observed contraction of daily activities associated with ageing. Several questionnaires are available to assess LSM in different contexts: the University of Alabama Life-Space Assessment and the Life-Space Questionnaire (community settings), the Nursing Home Life-Space Diameter (nursing home settings) and Life Space at Home (for house-bound populations). Some studies using GPS trackers to calculate life-space parameters reported promising results. Although these techniques reduce data collection burden, battery life and older people's willingness to wear a tracker require further improvement before they can be used more widely. Regardless of the assessment method used, LSM was associated with measures of functional and cognitive abilities, nursing home admission and mortality. The current availability of instruments, the ongoing development of less burdensome data collection techniques, and evidence of construct validity support a case for promoting integration of LSM assessments into geriatric research studies and clinical practice. Ultimately, this will provide a more holistic view on older people's health and wellbeing. [ABSTRACT FROM AUTHOR]

Background--Transradial access is associated with reduced access site-related bleeding complications and mortality post percutaneous coronary intervention. The objective of this study is to examine the relationship between access site practice and clinical outcomes and how this may be influenced by operator and center experience/expertise. Methods and Results--The influence of operator and center experience/expertise was studied on 30-day mortality, in-hospital major adverse cardiovascular events (a composite of in-hospital mortality and in-hospital myocardial infarction and target vessel revascularization) and in-hospital major bleeding based on access site adopted (radial versus femoral). Operator/center experience/expertise were defined by both total volume and transradial access proportion. A total of 164 395 procedures between 2012 and 2013 in the National Health Service in England and Wales were analyzed. After case-mix adjustment, transradial access was associated with an average odds reduction of 39% for 30-day mortality compared with transfemoral access (odds ratio, 0.61; 95% confidence interval, 0.55- 0.68; P<0.001). The magnitude of this risk reduction was modified by increases in total procedural volume and radial proportion at the operator level (odds ratio reduction of 11% per 100 extra procedures, 95% confidence interval, 3%-19%; odds ratio reduction of 6% per 10%-point increase in radial proportion, 95% confidence interval, 1%-11%) with no significant impact of operator radial volume, center total volume, center radial volume, and center radial proportion. Conclusions--The lower mortality associated with transradial access adoption relates to both the total procedural volume and the proportion of procedures undertaken radially by operator, with operators undertaking the greatest proportion of their procedures radially having the largest relative reduction in mortality risk. [ABSTRACT FROM AUTHOR]

Background: Patient outcomes in specialist burns units have been used as a metric of care needs and quality. Besides patient factors there are service factors that might influence Length of Stay (LOS) and mortality, e.g. pressure on beds. Although the bed needs of UK hospitals have dropped significantly over the past three decades, with changes in policies and practices, recent reports suggest that hospitals have 90% bed occupancy for 48 weeks of the year. In the UK, the specialist burn injury service is organised so that patients are assessed on arrival at hospital, and those needing admission are found a nearby bed in a suitable unit through the National Burn Bed Bureau. The aim of this study was to investigate the effect on outcomes of service pressures due to shortages of beds. Methods: We took an extract of the anonymised patient data from the specialised burn injury database, iBID, and created a new database based on matching that data with bed availability data provided by the national Burn Bed Bureau. Cox proportional hazard modelling was used for analysis to investigate if there is an impact of bed occupancy (a proxy measure of workload) on LOS. Results: Cox proportional hazard modelling indicated that half of the services in England and Wales are less likely to discharge a patient if the bed availability is high. Two of the services have abnormally high bed availability and LOS, therefore a model without these two services indicates a general reluctance to discharge patients when beds are available. Conclusions: It is possible that the effect we observed is a result of gaming as service providers are paid by the number of admissions. In addition, providers many not all give the same level of accuracy of bed availability information to the NBBB: some may under report availability, for example at times of high pressure on staff. Furthermore, burn services may not empty beds to avoid being filled up by work from other specialties, thus making them unable to admit a burn when referred. [ABSTRACT FROM AUTHOR]

Introduction Mortality among patients treated in hospital for burn is routinely examined, but none of the many models in use in the UK was developed using nationwide data. The aim of this research was to develop a prediction model using national data, representative of the British population. Methods Data were gathered from the international Burns Injury Database (iBID) and included 66,611 patients from England and Wales from 2003 to 2011. Core variables were selected following systematic review of the literature, expert consultation and then supplemented with variables selected through logistic regression. Discrimination and calibration of the model were assessed using the area under the receiver operating characteristic curve and the Hosmer–Lemeshow χ 2 test respectively. Results Overall mortality for the years of the study in England and Wales was 1.27%. Mortality was predicted by age (and quadratic term) total burn surface area, presence of inhalation injury, presence of existing disorders and category of injury. The model gave a discrimination area under the curve of 0.97 in both internal and external validation. The calibration of the model gave a Hosmer–Lemeshow χ 2 of 11.9 ( p = 0.3). Conclusion We have reported a strongly predictive and theoretically well-founded model of in-patient mortality using nine years of data from all burn care services in England and Wales. We recommend this model for British burn service development and for international consideration of the variables to use in developing similar models with other data sources. [ABSTRACT FROM AUTHOR]

Abstract: The majority of Western countries have reported large falls in cardiovascular diseases (CVD) mortality rates since the 1970s. Yet since the 1980s, they have also experienced two-fold or three-fold increases in the prevalence of obesity and type 2 diabetes - both considered substantial risk factors for CVD. So why have these increasing risks apparently not impacted on CVD mortality falls? This viewpoint outlines the main factors involved; examines recent trends and apparent contradictions; offers some explanations for the trends; discusses how more usefully complex epidemiological models might lead to clearer evidence; offers some explanations for the trends; and explores the implications for CVD prevention. [Copyright &y& Elsevier]

The article discusses research which investigated premature mortality and primary care quality under the British Quality and Outcomes Framework (QOF). Topics explored include the recorded patient outcomes associated with QOF, the identification of all causes of mortality such as diabetes and heart failure, and the observed link between high mortality rate and urban location.

Background: The transradial access (TRA) site has become the default access site for percutaneous coronary intervention in the United Kingdom, with randomized trials and national registry data showing reductions in mortality associated with TRA use. This study evaluates regional changes in access site practice in England and Wales over time, examines whether changes in access site practice have been uniform nationally and across different patient subgroups, and provides national estimates for the potential number of lives saved or lost associated with regional differences in access site practice.Methods and Results: Using the British Cardiovascular Intervention Society database, we investigated outcomes for growth of TRA in different regions in England and Wales in 448 853 patients who underwent percutaneous coronary intervention from 2005 to 2012. Multiple logistic regression was used to quantify the effect of TRA on 30-day mortality and quantify lives saved and lost by differences in TRA adoption. TRA use increased from 14.0% to 58.6% in 417 038 PCI patients with large variations in different parts of the country. TRA was independently associated with a decreased risk of 30-day mortality (odds ratio=0.70; 95% confidence interval=0.66-0.74), with significant but small differences observed across different regions. The number of estimated lives saved was 450 (95% confidence interval=275-650), and we estimate that an additional 264 (95% confidence interval=153-399) lives would have been saved if TRA adoption were uniform nationally.Conclusions: TRA has become the dominant percutaneous coronary intervention approach in the United Kingdom, with a wide variation in different parts of the country. Changes in practice have contributed to mortality reductions, and inequalities have resulted in missed opportunities for further improvements. [ABSTRACT FROM AUTHOR]

Introduction Predicting mortality from burn injury has traditionally employed logistic regression models. Alternative machine learning methods have been introduced in some areas of clinical prediction as the necessary software and computational facilities have become accessible. Here we compare logistic regression and machine learning predictions of mortality from burn. Methods An established logistic mortality model was compared to machine learning methods (artificial neural network, support vector machine, random forests and naïve Bayes) using a population-based (England & Wales) case-cohort registry. Predictive evaluation used: area under the receiver operating characteristic curve; sensitivity; specificity; positive predictive value and Youden's index. Results All methods had comparable discriminatory abilities, similar sensitivities, specificities and positive predictive values. Although some machine learning methods performed marginally better than logistic regression the differences were seldom statistically significant and clinically insubstantial. Random forests were marginally better for high positive predictive value and reasonable sensitivity. Neural networks yielded slightly better prediction overall. Logistic regression gives an optimal mix of performance and interpretability. Discussion The established logistic regression model of burn mortality performs well against more complex alternatives. Clinical prediction with a small set of strong, stable, independent predictors is unlikely to gain much from machine learning outside specialist research contexts. [ABSTRACT FROM AUTHOR]

Background Transradial access (TRA) has been associated with reduced access site–related bleeding complications and mortality after percutaneous coronary intervention (PCI). It is unclear, however, whether these observed benefits are influenced by baseline bleeding risk. Objectives This study investigated the relationship between baseline bleeding risk, TRA utilization, and procedure-related outcomes in patients undergoing PCI enrolled in the British Cardiovascular Intervention Society database. Methods Baseline bleeding risk was calculated by using modified Mehran bleeding risk scores in 348,689 PCI procedures performed between 2006 and 2011. Four categories for bleeding risk were defined for the modified Mehran risk score (MMRS): low (<10), moderate (10 to 14), high (15 to 19), and very high (≥20). The impact of baseline bleeding risk on 30-day mortality and its relationship with access site were studied. Results TRA was independently associated with a 35% reduction in 30-day mortality risk (odds ratio [OR]: 0.65 [95% confidence interval (CI): 0.59 to 0.72]; p < 0.0001), with the magnitude of mortality reduction related to baseline bleeding risk (MMRS <10, OR: 0.73 [95% CI: 0.62 to 0.86]; MMRS ≥20, OR: 0.53 [95% CI: 0.47 to 0.61]). In patients with an MMRS <10, TRA was used in 71,771 (43.2%) of 166,083 PCI procedures; TRA was used in 8,655 (40.1%) of 21,559 PCI procedures in patients with an MMRS ≥20, illustrating that TRA was used less in those at highest risk from bleeding complications (p < 0.0001). Conclusions TRA was independently associated with reduced 30-day mortality, and the magnitude of this effect was related to baseline bleeding risk; those at highest risk of bleeding complications gained the greatest benefit from adoption of TRA during PCI. [ABSTRACT FROM AUTHOR]