Important factors in predicting mortality outcome from stroke: Findings from the Anglia Stroke Clinical Network Evaluation Study

Background: although variation in stroke service provision and outcomes have been previously investigated, it is less well known what service characteristics are associated with reduced short- and medium-term mortality. Methods: data from a prospective multicentre study (2009–12) in eight acute regional NHS trusts with a catchment population of about 2.6 million were used to examine the prognostic value of patient-related factors and service characteristics on stroke mortality outcome at 7, 30 and 365 days post stroke, and time to death within 1 year. Results: a total of 2,388 acute stroke patients (mean (standard deviation) 76.9 (12.7) years; 47.3% men, 87% ischaemic stroke) were included in the study. Among patients characteristics examined increasing age, haemorrhagic stroke, total anterior circulation stroke type, higher prestroke frailty, history of hypertension and ischaemic heart disease and admission hyperglycaemia predicted 1-year mortality. Additional inclusion of stroke service characteristics controlling for patient and service level characteristics showed varying prognostic impact of service characteristics on stroke mortality over the disease course during first year after stroke at different time points. The most consistent finding was the benefit of higher nursing levels; an increase in one trained nurses per 10 beds was associated with reductions in 30-day mortality of 11–28% (P < 0.0001) and in 1-year mortality of 8–12% (P < 0.001). Conclusions: there appears to be consistent and robust evidence of direct clinical benefit on mortality up to 1 year after acute stroke of higher numbers of trained nursing staff over and above that of other recognised mortality risk factors

Evaluation of stroke services in Anglia Stroke Clinical Network to examine the variation in acute services and stroke outcomes.

BACKGROUND: Stroke is the third leading cause of death in developed countries and the leading cause of long-term disability worldwide. A series of national stroke audits in the UK highlighted the differences in stroke care between hospitals. The study aims to describe variation in outcomes following stroke and to identify the characteristics of services that are associated with better outcomes, after accounting for case mix differences and individual prognostic factors. METHODS/DESIGN: We will conduct a cohort study in eight acute NHS trusts within East of England, with at least one year of follow-up after stroke. The study population will be a systematically selected representative sample of patients admitted with stroke during the study period, recruited within each hospital. We will collect individual patient data on prognostic characteristics, health care received, outcomes and costs of care and we will also record relevant characteristics of each provider organisation. The determinants of one year outcome including patient reported outcome will be assessed statistically with proportional hazards regression models. Self (or proxy) completed EuroQol (EQ-5D) questionnaires will measure quality of life at baseline and follow-up for cost utility analyses. DISCUSSION: This study will provide observational data about health service factors associated with variations in patient outcomes and health care costs following hospital admission for acute stroke. This will form the basis for future RCTs by identifying promising health service interventions, assessing the feasibility of recruiting and following up trial patients, and provide evidence about frequency and variances in outcomes, and intra-cluster correlation of outcomes, for sample size calculations. The results will inform clinicians, public, service providers, commissioners and policy makers to drive further improvement in health services which will bring direct benefit to the patients.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

Characterisation of the expression and function of the GM-CSF receptor α-chain in mice

The granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine able to regulate a variety of cell functions including differentiation of macrophages and granulocytes, dendritic cell development and the maintenance of homeostasis. It binds specifically to its receptor, which is composed of a cytokine-specific α-chain (GM-CSF receptor α-chain, GMRα) and a β-chain shared with the receptors for interleukin-3 and interleukin-5. In this report, we present a comprehensive study of GMRα in the mouse. We have found that the mouse GMRα is polymorphic and alternatively spliced. In the absence of specific antibodies, we generated a novel chimeric protein containing the Fc fragment of human IgG1 coupled to mouse GM-CSF, which was able to specifically bind to GMRα and induce proliferation of GMRα-transduced Ba/F3 cells. We used this reagent to perform the first detailed FACS study of the surface expression of mouse GMRα by leucocytes. Highest expression was found on monocytes and granulocytes, and variable expression on tissue macrophages. The GM-CSF receptor in mice is specifically expressed by myeloid cells and is useful for the detection of novel uncharacterised myeloid populations. The ability to detect GM-CSF receptor expression in experimental studies should greatly facilitate the analysis of its role in immune pathologies

Modified early warning score and risk of mortality after acute stroke

Objective:  An accurate prediction tool may facilitate optimal management of patients with acute stroke from an early stage. We evaluated the association between admission modified early warning score (MEWS) and mortality in patients with acute stroke. Method:  Data from the Anglia Stroke Clinical Network Evaluation Study (ASCNES) were analysed. We evaluated the association between admission MEWS and four outcomes; in-patient, 7-day, 30-day and 1-year mortality. Logistic regression models were used to calculate the odds of all mortality timeframes, whereas Cox proportional hazards models were used to calculate mortality at 1 year. Five univariate and multivariate models were constructed, adjusting for confounders. Patients with a moderate (2-3) or high (≥4) scores were compared to patients with a low score (0-1). Results:  The study population consisted of 2,006 patients. A total of 1196 patients had low MEWS, 666 had moderate MEWS and 144 had a high MEWS. A high MEWS was associated with increased mortality as an in-patient (OR 4.93, 95% CI: 2.88–8.42), at 7 days (OR 7.53, 95% CI: 4.24 – 13.38), at 30 days (OR 5.74, 95% CI: 3.38 – 9.76) and 1-year (HR 2.52, 95% CI 1.88 – 3.39). At 1 year, model 5 had a 1.02 OR (95% CI 0.83 – 1.24) with moderate MEWS and 2.52 (95% CI 1.88 – 3.39) with high MEWS. Conclusion:  Elevated MEWS on admission is a potential marker for acute-stroke mortality and may therefore be a useful risk prediction tool, able to guide clinicians attempting to prognosticate outcomes for patients with acute-stroke

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Hyperglycaemia and the SOAR stroke score in predicting mortality

Background: We assessed the association between admission blood glucose levels and acute stroke mortality and examined whether there was any incremental value of adding glucose status to the validated acute stroke mortality predictor – the SOAR (stroke subtype, Oxford Community Stroke Project classification, age, and pre-stroke modified Rankin) score. Methods: Data from Norfolk and Norwich University Hospital stroke and Transient Ischaemic Attack register (2003–2013) and Anglia Stroke Clinical Network Evaluation Study (2009–2012) were analysed. Multivariable logistic regression analysis assessed the association between admission blood glucose levels with inpatient and 7-day mortality. The prognostic ability of the SOAR score was then compared with the SOAR with glucose score. Results: A total of 5575 acute stroke patients (ischaemic stroke: 89.2%) with mean age (standard deviation) of 76.97 ( ± 11.88 ) years were included. Both borderline hyperglycaemia (7.9–11.0 mmol/L) and hyperglycaemia (>11.0 mmol/L) when compared to normoglycaemia (4.0–7.8 mmol/L) were associated with both 7-day and inpatient mortality after controlling for sex, age, Oxford Community Stroke Project classification and pre-stroke modified Rankin score. Both the SOAR stroke score and SOAR-G score were good predictors of inpatient stroke mortality [area under the curve: 0.82 (95% confidence interval: 0.81–0.84) and 0.83 (95% confidence interval: 0.81–0.84)], respectively. These scores were also good at predicting outcomes in both patients with and without diabetes. Conclusion: High blood glucose levels at admission were associated with worse acute stroke mortality outcomes. The constituents of the SOAR stroke score were good at predicting mortality after stroke

Time to computerized tomography scan, age, and mortality in acute stroke

Background: Time to computerized tomography (CT) is important to institute appropriate and timely hyper-acute management in stroke. We aimed to evaluate mortality outcomes in relation to age and time to CT scan. Methods: We used routinely collected data in eight National Health Service Trusts in East of England between September 2008 and April 2011. Stroke cases were prospectively identified and confirmed. Odds ratios for unadjusted and adjusted models for age categories(24 hours) and the in-hospital and early(<7 days) mortality outcomes were calculated. Results: Of 7,693 patients (mean age 76.1 years, 50% male) included, 1,151(16%) died as inpatient and 336(4%) died within seven days. Older patients and those admitted from care home had a significantly longer time from admission until CT (p<0.001). Patients who had earlier CT scans were admitted to stroke units more frequently (p<0.001) but had higher in-patient(p<0.001) and seven-day mortality(p<0.001). Whilst older age was associated with increased odds of mortality outcomes, longer time to CT was associated with significantly reduced within 7 day mortality(corresponding ORs for above time periods were 1.00, 0.61(0.39-0.95), 0.39(0.24-0.64) and 0.16(0.08-0.33) and in-hospital mortality(ORs 1.00, 0.86(0.64-1.15), 0.57(0.42-0.78) and 0.71(0.52-0.98)). Conclusions: Older age was associated with a significantly longer time to CT. However, using CT scan time as a benchmarking tool in stroke may have inherent limitations and it does not appear to be a suitable quality marker