Estimating the number of UK stroke patients eligible for endovascular thrombectomy

Introduction: Endovascular thrombectomy (EVT) is a highly effective treatment for acute ischemic stroke due to large arterial occlusion. Routine provision will require major changes in service configuration and workforce. An important first step is to quantify the population of stroke patients that could benefit. We estimated the annual UK population suitable for EVT using standard or advanced imaging (AI) for patient selection. Patients and Methods: Evidence from randomised control trials and national registries was combined to estimate UK stroke incidence and define a decision-tree describing the EVT eligible population. Results: Between 9,620 and 10,920 UK stroke patients (approximately 10% of stroke admissions) would be eligible for EVT annually. The majority (9,140 to 9,620) would present within 4 hours of onset and be suitable for intravenous thrombolysis. Advanced Imaging would exclude 500 patients presenting within 4 hours, but identify an additional 1,310 patients as eligible who present later. Discussion: Information from randomised control trials and large registry data provided the evidence criterion for 9 of the 12 decision points. The best available evidence was used for 2 decision-points with sensitivity analyses to determine how key branches of the tree affected estimates. Using the mid-point estimate for eligibility (9.6% of admissions) and assuming national EVT coverage, 4,280 patients would have reduced disability. Conclusion: A model combining published trials and register data suggests approximately 10% of all stroke admissions in the UK are eligible for EVT. The use of AI based on current published evidence did not have a major impact on overall numbers, but could alter eligibility status for 16% of cases

Probability distributions for quantum stress tensors in four dimensions

We treat the probability distributions for quadratic quantum fields, averaged with a Lorentzian test function, in four-dimensional Minkowski vacuum. These distributions share some properties with previous results in two-dimensional spacetime. Specifically, there is a lower bound at a finite negative value, but no upper bound. Thus arbitrarily large positive energy density fluctuations are possible. We are not able to give closed form expressions for the probability distribution, but rather use calculations of a finite number of moments to estimate the lower bounds, the asymptotic forms for large positive argument, and possible fits to the intermediate region. The first 65 moments are used for these purposes. All of our results are subject to the caveat that these distributions are not uniquely determined by the moments. However, we also give bounds on the cumulative distribution function that are valid for any distribution fitting these moments.We apply the asymptotic form of the electromagnetic energy density distribution to estimate the nucleation rates of black holes and of Boltzmann brains.Comment: 26 pages, 2 figure

Nonphysician providers in hospital medicine: Not so fast

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64916/1/584_ftp.pd

Factors that influence clinicians’ decisions to offer intravenous alteplase in acute ischemic stroke patients with uncertain treatment indication:Results of a discrete choice experiment

Background: Treatment with intravenous alteplase for eligible patients with acute ischemic stroke is underused, with variation in treatment rates across the UK. This study sought to elucidate factors influencing variation in clinicians’ decision-making about this thrombolytic treatment. Methods: A discrete choice experiment using hypothetical patient vignettes framed around areas of clinical uncertainty was conducted with UK-based clinicians. Mixed logit regression analyses were conducted on the data. Results: A total of 138 clinicians completed the discrete choice experiment. Seven patient factors were individually predictive of increased likelihood of immediately offering IV alteplase (compared to reference levels in brackets): stroke onset time 2 h 30 min [50 min]; pre-stroke dependency mRS 3 [mRS 4]; systolic blood pressure 185 mm/Hg [140 mm/Hg]; stroke severity scores of NIHSS 5 without aphasia, NIHSS 14 and NIHSS 23 [NIHSS 2 without aphasia]; age 85 [68]; Afro-Caribbean [white]. Factors predictive of withholding treatment with IV alteplase were: age 95 [68]; stroke onset time of 4 h 15 min [50 min]; severe dementia [no memory problems]; SBP 200 mm/Hg [140 mm/Hg]. Three clinician-related factors were predictive of an increased likelihood of offering IV alteplase (perceived robustness of the evidence for IV alteplase; thrombolyzing more patients in the past 12 months; and high discomfort with uncertainty) and one with a decreased likelihood (high clinician comfort with treating patients outside the licensing criteria). Conclusions: Both patient- and clinician-related factors have a major influence on the use of alteplase to treat patients with acute ischemic stroke. Clinicians’ views of the evidence, comfort with uncertainty and treating patients outside the license criteria are important factors to address in programs that seek to reduce variation in care quality regarding treatment with IV alteplase. Further research is needed to further understand the differences in clinical decision-making about treating patients with acute ischemic stroke with IV alteplase

B-blockers, calcium antagonists, and mortality in stable coronary artery disease: An international cohort study

Aims: The effect of first-line antianginal agents, β-blockers, and calcium antagonists on clinical outcomes in stable coronary artery disease (CAD) remains uncertain. Methods and results We analysed the use of β-blockers or calcium antagonists (baseline and annually) and outcomes in 22 006 stable CAD patients (enrolled 2009–2010) followed annually to 5 years, in the CLARIFY registry (45 countries). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death and the composite of cardiovascular death/non-fatal myocardial infarction (MI). After multivariable adjustment, baseline β-blocker use was not associated with lower all-cause death [1345 (7.8%) in users vs. 407 (8.4%) in non-users; hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.84–1.06; P = 0.30]; cardiovascular death [861 (5.0%) vs. 262 (5.4%); HR 0.91, 95% CI 0.79–1.05; P = 0.20]; or cardiovascular death/non-fatal MI [1272 (7.4%) vs. 340 (7.0%); HR 1.03, 95% CI 0.91–1.16; P = 0.66]. Sensitivity analyses according to β-blocker use over time and to prescribed dose produced similar results. Among prior MI patients, for those enrolled in the year following MI, baseline β-blocker use was associated with lower all-cause death [205 (7.0%) vs. 59 (10.3%); HR 0.68, 95% CI 0.50–0.91; P = 0.01]; cardiovascular death [132 (4.5%) vs. 49 (8.5%); HR 0.52, 95% CI 0.37–0.73; P = 0.0001]; and cardiovascular death/non-fatal MI [212 (7.2%) vs. 59 (10.3%); HR 0.69, 95% CI 0.52–0.93; P = 0.01]. Calcium antagonists were not associated with any difference in mortality. Conclusion In this contemporary cohort of stable CAD, β-blocker use was associated with lower 5-year mortality only in patients enrolled in the year following MI. Use of calcium antagonists was not associated with superior mortality, regardless of history of MI

Evaluation of an Extended Stroke Rehabilitation Service (EXTRAS): A Randomized Controlled Trial and Economic Analysis

Background and Purpose— There is limited evidence to guide rehabilitation to meet the longer term needs of stroke survivors. The clinical effectiveness and cost-effectiveness of an extended stroke rehabilitation service (EXTRAS) provided following early supported discharge were determined. Methods— EXTRAS was a pragmatic parallel-group observer-blind randomized controlled trial involving 19 UK centers. Patients with stroke were individually randomized to receive EXTRAS or usual care at discharge from early supported discharge. Five EXTRAS reviews were provided by an early supported discharge team member between one and 18 months, usually by telephone. Reviews consisted of a semi-structured interview assessing progress, rehabilitation needs, and service provision, with goal setting and action planning. The primary outcome was performance in extended activities of daily living (Nottingham EADL Scale) at 24 months post-randomization. The Nottingham EADL Scale is scored 0 to 66, with higher scores indicating better performance in these activities. Cost-effectiveness was estimated using resource utilization costs and Quality Adjusted Life Years. Analyses were intention to treat. Results— Between January 9, 2013 and October 26, 2015, 573 participants were randomized (EXTRAS, n=285; usual care, n=288). Mean 24 month Nottingham EADL Scale scores were EXTRAS (n=219) 40.0 (SD 18.1) and usual care (n=231) 37.2 (SD 18.5) giving an adjusted mean difference of 1.8 (95% CI, –0.7 to 4.2). 1155/1338 (86%) of expected EXTRAS reviews were undertaken. Over 24 months, the mean cost of resource utilization was lower in the intervention group: –£311 (–$450 [95$4764 to $4033]). EXTRAS provided more Quality Adjusted Life Years (0.07 [95$28 940] per Quality Adjusted Life Years), there was a 90% chance that EXTRAS could be considered cost-effective. Conclusions— EXTRAS did not significantly improve stroke survivors’ performance in extended activities of daily living. However, given the impact on costs and Quality Adjusted Life Years, EXTRAS may be an affordable addition to improve stroke care

Evaluation of diet pattern and weight gain in postmenopausal women enrolled in the Women’s Health Initiative Observational Study

Abstract It is unclear which of four popular contemporary diet patterns is best for weight maintenance among postmenopausal women. Four dietary patterns were characterised among postmenopausal women aged 49–81 years (mean 63·6 ( sd 7·4) years) from the Women’s Health Initiative Observational Study: (1) a low-fat diet; (2) a reduced-carbohydrate diet; (3) a Mediterranean-style (Med) diet; and (4) a diet consistent with the US Department of Agriculture’s Dietary Guidelines for Americans (DGA). Discrete-time hazards models were used to compare the risk of weight gain (≥10 %) among high adherers of each diet pattern. In adjusted models, the reduced-carbohydrate diet was inversely related to weight gain (OR 0·71; 95 % CI 0·66, 0·76), whereas the low-fat (OR 1·43; 95 % CI 1·33, 1·54) and DGA (OR 1·24; 95 % CI 1·15, 1·33) diets were associated with increased risk of weight gain. By baseline weight status, the reduced-carbohydrate diet was inversely related to weight gain among women who were normal weight (OR 0·72; 95 % CI 0·63, 0·81), overweight (OR 0·67; 95 % CI 0·59, 0·76) or obese class I (OR 0·63; 95 % CI 0·53, 0·76) at baseline. The low-fat diet was associated with increased risk of weight gain in women who were normal weight (OR 1·28; 95 % CI 1·13, 1·46), overweight (OR 1·60; 95 % CI 1·40, 1·83), obese class I (OR 1·73; 95 % CI 1·43, 2·09) or obese class II (OR 1·44; 95 % CI 1·08, 1·92) at baseline. These findings suggest that a low-fat diet may promote weight gain, whereas a reduced-carbohydrate diet may decrease risk of postmenopausal weight gain

An observational study of patient characteristics associated with the mode of admission to acute stroke services in North East, England

Objective Effective provision of urgent stroke care relies upon admission to hospital by emergency ambulance and may involve pre-hospital redirection. The proportion and characteristics of patients who do not arrive by emergency ambulance and their impact on service efficiency is unclear. To assist in the planning of regional stroke services we examined the volume, characteristics and prognosis of patients according to the mode of presentation to local services. Study design and setting A prospective regional database of consecutive acute stroke admissions was conducted in North East, England between 01/09/10-30/09/11. Case ascertainment and transport mode were checked against hospital coding and ambulance dispatch databases. Results Twelve acute stroke units contributed data for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by private transport or non-emergency ambulance; 252 unknown mode. Emergency ambulance patients were older (76 vs 69 years), more likely to be from institutional care (10% vs 1%) and experiencing total anterior circulation symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency admission (11% vs 4%). However patients attending without emergency ambulance had lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1% vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly dependent patients were admitted by emergency ambulance, but none received thrombolysis. Conclusion Presentations of new stroke without emergency ambulance involvement were not unusual but were associated with a better outcome due to younger age, milder neurological impairment and lower levels of pre-stroke dependency. Most patients with a high level of pre-stroke dependency arrived by emergency ambulance but did not receive thrombolysis. It is important to be aware of easily identifiable demographic groups that differ in their potential to gain from different service configurations

Blood pressure variability and cardiovascular risk in the PROspective study of pravastatin in the elderly at risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects

Genetic risk prediction of atrial fibrillation

Background—Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. Methods—To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 referents. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1x10-3 to <1x10-8 in a prior independent genetic association study. Results—Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13-1.46; P=1.5x10-4) to 1.67 (25 variants; 95%CI, 1.47-1.90; P=9.3x10-15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum ΔC statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95%CI, 1.39-4.58; P=2.7x10-3). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20-4.40; P=0.01). Conclusions—Comprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms