Autumn Weather and Winter Increase in Cerebrovascular Disease Mortality.

Mortality from cerebrovascular disease increases in winter but the cause is unclear. Ireland's oceanic climate means that it infrequently experiences extremes of weather. We examined how weather patterns relate to stroke mortality in Ireland. Seasonal data for Sunshine (% of average), Rainfall (% of average) and Temperature (degrees Celsius above average) were collected for autumn (September-November) and winter (December-February) using official Irish Meteorological Office data. National cerebrovascular mortality data was obtained from Quarterly Vital Statistics. Excess winter deaths were calculated by subtracting (nadir) 3rd quarter mortality data from subsequent 1st quarter data. Data for 12 years were analysed, 2002-2014. Mean winter mortality excess was 24.7%. Winter mortality correlated with temperature (r=.60, p=0.04). Rise in winter mortality correlated strongly with the weather in the preceding autumn (Rainfall: r=-0.19 p=0.53, Temperature: r=-0.60, p=0.03, Sunshine, r=0.58, p=0.04). Winter cerebrovascular disease mortality appears higher following cool, sunny autumns.

Increased thrombin generation potential in symptomatic versus asymptomatic moderate or severe carotid stenosis and relationship with cerebral microemboli.

INTRODUCTION: The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed. METHODS: Plasma thrombin generation parameters from patients with moderate or severe (≥ 50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤ 4 weeks) and late phases (≥ 3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic, 46 'early symptomatic' and 35 'late symptomatic' patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p = 0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p = 0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p = 0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter 'time-to-peak thrombin' than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup. DISCUSSION: Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis.

Ischaemic stroke or TIA in older subjects associated with impaired dynamic blood pressure control in the absence of severe large artery stenosis.

BACKGROUND: older subjects may require higher baseline blood pressures to maintain cerebral perfusion. We investigated whether episodic hypotension is associated with tissue infarction in subjects with syncopal symptoms at stroke onset. METHODS: over 30 months, all acute strokes/TIAs were prospectively screened for symptoms of syncope or presyncope at stroke onset. Subjects with severe large vessel stenosis were excluded, while cases were referred for syncope unit investigation. All underwent 1.5 T MRI acutely, and suspected borderzone infarctions (BZI) were confirmed through Matlab-derived perfusion software. Case-control comparison was derived from stroke controls with no prior syncope history. RESULTS: thirty-eight of 772 stroke patients described presyncope or syncope at stroke onset and had patent large vessels (4.9% of all strokes). Median age was 72 years (IQR 21.4). Twenty-two patients (58%) were prescribed antihypertensive agents at symptom onset. Twenty-six (68.4%) reported focal neurology <24 h in duration. 63.2% (n = 24) of cases reported prior syncope history, compared with 33% (N = 103) of controls, P < 0.001. Cases exhibited greater orthostatic BP drop than controls, P < 0.05 Twenty-four patients were diagnosed with vasovagal syncope through head-up tilt symptom reproduction, 9 with orthostatic hypotension, 4 with cardiac syncope and 1 with carotid sinus syndrome. Nineteen (50%) patients had an acute infarct on MRI, 14 of these were in the arterial borderzone (73.6%). The BZI group were significantly older than the non-BZI group, 79.2 yrs versus 63.3 yrs, P = 0.002. CONCLUSION: subjects reporting hypotensive symptoms at stroke onset have a higher prevalence of borderzone infarction, despite being normotensive or hypertensive at baseline.

In-hospital stroke: characteristics and outcomes.

In-hospital stroke (IS) made up 6.5% of strokes recorded in the Irish National Stroke Register in 2012. International research has demonstrated poorer outcomes post IS compared to out of hospital stroke (OS). We aimed to profile all IS and OS over a 22 month period and compare the two groups by gathering data from the HIPE portal stroke register. The study site is a primary stroke centre. IS represented 11% (50/458) of total strokes with over half (27/50, 54%) admitted initially with medical complaints. IS patients had a significantly longer length of stay (79.2 +/- 87.4 days vs. 21.9 +/- 45.9 days, p < 0.01) and higher mortality (13/50 vs. 39/408, p < 0.01). Patients in the IS group were also less likely to receive stroke unit care (1/50 vs. 136/408, p < 0.01). This study demonstrates the significant morbidity and mortality associated with IS and highlights the need for efforts to be made to optimize identification and management of acute stroke in this cohort.

Evolution of Carotid Surgical Practice in the last Decade.

Stroke units provide immediate care and appropriate intervention in the evolving stroke. The aims of this study were to review the practice of carotid endarterectomy (CEA) before and after the establishment of a Stroke Unit in St. James's Hospital. Prior to the introduction of the Stroke Unit, 263 CEA's were performed over a five-year period. 139/263 (53%) of these were for symptomatic disease. 229 were performed in the five years since. 179/229 (78%) of these were for symptomatic disease. The 30-day stroke and death rates were < 2% before the introduction of the Stroke Unit, and have remained unchanged. Since the introduction of the Stroke Unit, there has been a slight decrease in the overall number of CEA's performed with a 25% increase in the proportion of endarterectomies performed for symptomatic disease. Despite the reduction in surgery for asymptomatic disease the overall 30-day stroke and death rate remains excellent at 2/229 (2%).

Increased endothelial activation in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic-signal-negative patient subgroups.

BACKGROUND AND PURPOSE: von Willebrand factor propeptide (VWF:Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals (MESs) detected on transcranial Doppler ultrasound is unknown. METHODS: In this multicentre observational analytical study, plasma VWF:Ag and VWF:Ag II levels in patients with ≥50% asymptomatic carotid stenosis were compared with those from patients with ≥50% symptomatic carotid stenosis in the 'early' (≤4 weeks) and 'late' (≥3 months) phases after transient ischaemic attack or ischaemic stroke. Endothelial activation was also longitudinally assessed in symptomatic patients during follow-up. Transcranial Doppler ultrasound monitoring classified patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic patients were compared with those from 46 early symptomatic and 35 late phase symptomatic carotid stenosis patients, 23 of whom had undergone carotid intervention. VWF:Ag II levels were higher in early (12.8 µg/ml; P < 0.001), late (10.6 µg/ml; P = 0.01) and late post-intervention (10.6 µg/ml; P = 0.038) symptomatic patients than asymptomatic patients (8.9 µg/ml). VWF:Ag levels decreased in symptomatic patients followed up from the early to late phase after symptom onset (P = 0.048). Early symptomatic MES-negative patients had higher VWF: Ag II levels (13.3 vs. 9.0 µg/ml; P < 0.001) than asymptomatic MES-negative patients. CONCLUSIONS: Endothelial activation is enhanced in symptomatic versus asymptomatic carotid stenosis patients, in early symptomatic versus asymptomatic MES-negative patients, and decreases over time in symptomatic patients. VWF:Ag II levels are a more sensitive marker of endothelial activation than VWF:Ag levels in carotid stenosis. The potential value of endothelial biomarkers and concurrent cerebral MES detection at predicting stroke risk in carotid stenosis warrants further study.

Hospital size, remoteness and stroke outcome.

INTRODUCTION: Previous studies have shown an association between number of stroke admissions and outcomes. Small hospitals often support more remote areas and we studied national data to determine if an association exists between hospital remoteness and stroke care. METHODS: Data from the Irish National Audit of Stroke (INAS) on average stroke admissions, adjusted mortality for ischaemic stroke, thrombolysis rate and proportion with door to needle (DTN) ≤45 min were analysed. Hospital remoteness was quantified by distance to the next hospital, nearest neurointerventional centre and location within 10 km of the national motorway network. RESULTS: Data for 23 of 24 stroke services were evaluated. Median number of strokes admitted per year was 186 (range 84-497). Nine hospitals (39%) admitted ≥200 stroke patients per year (mean 332). Average adjusted mortality (7.0 vs. 7.3, P = 0.67 t-test), mean thrombolysis rate (12.1% vs. 9.2%, P = 0.09) and mean proportion of patients treated ≤45 min (40.4% vs. 31.3%, P = 0.2) did not differ significantly between higher and lower volume hospitals.Hospitals close to the motorway network (n = 15) had a higher mean thrombolysis rate (11.9% vs. 7.5%, P = 0.01 t-test) and proportion DTN ≤45 min (43.7-18.4%, P < 0.001).Number of stroke admissions did not correlate with mortality (r = 0.06, P = 0.78), DTN (r = 0.12, P = 0.95) or thrombolysis rate (r = 0.35, P = 0.20). Distance to next hospital correlated strongly negatively with DTN (r = -0.47, P = 0.02) and thrombolysis rate (-0.43, P = 0.04). CONCLUSION: Remoteness of hospitals is associated with worse measures of stroke outcome and management.

Inflammatory cytokines, high-sensitivity C-reactive protein, and risk of one-year vascular events, death, and poor functional outcome after stroke and transient ischemic attack.

BACKGROUND: Inflammation driven by pro-inflammatory cytokines is a new therapeutic target in coronary disease. Few data exist on the association of key upstream cytokines and post-stroke recurrence. In a prospective cohort study, we investigated the association between pivotal cytokines, high-sensitivity C-reactive protein (hsCRP) and one-year outcomes. METHODS: BIO-STROKETIA is a multi-center prospective cohort study of non-severe ischemic stroke (modified Rankin score ≤ 3) and transient ischemic attack. Controls were patients with transient symptoms attending transient ischemic attack clinics with non-ischemic final diagnosis. Exclusion criteria were severe stroke, infection, and other pro-inflammatory disease; hsCRP and cytokines (interleukin (IL) 6, IL-1ß, IL-8, IL-10, IL-12, interferon-γ (IFN-γ), tumor-necrosis factor-α (TNF-α)) were measured. The primary outcome was one-year recurrent stroke/coronary events (fatal and non-fatal). RESULTS: In this study, 680 patients (439 stroke, 241 transient ischemic attack) and 68 controls were included. IL-6, IL-1ß, IL-8, IFN-γ, TNF-α, and hsCRP were higher in stroke/transient ischemic attack cases (p ≤ 0.01 for all). On multivariable Cox regression, IL-6, IL-8, and hsCRP independently predicted one-year recurrent vascular events (adjusted hazard ratios (aHR) per-quartile increase IL-6 1.31, confidence interval (CI) 1.02-1.68, p = 0.03; IL-8 1.47, CI 1.15-1.89, p = 0.002; hsCRP 1.28, CI 1.01-1.62, p = 0.04). IL-6 (aHR 1.98, CI 1.26-3.14, p = 0.003) and hsCRP (aHR 1.81, CI 1.20-2.74, p = 0.005) independently predicted one-year fatality. IL-6 and hsCRP (adjusted odds ratio per-unit increase 1.02, CI 1.01-1.04) predicted poor functional outcome, with a trend for IL-1ß (p = 0.054). CONCLUSION: Baseline inflammatory cytokines independently predicted late recurrence, supporting a rationale for randomized trials of anti-inflammatory agents for prevention after stroke and suggesting that targeted therapy to high-risk patients with high baseline inflammation may be beneficial.

The interaction between specific and general information in category learning and representation: unitization and parallel interactive processing.

We investigated the effects of specific stimulus information on the use of rule information in a category learning task in 2 experiments, one presented here and an intercategory transfer task reported in an earlier article. In the present experiment photograph--name combinations, called identifiers, were associated with 4 demographic attributes. The same attribute information was shown to all participants. However, for one group of participants, half of the identifiers were paired with attribute values repeated over presentation blocks. For the other group the identifier information was new for each presentation block. The first group performed less well than the second group on stimuli with nonrepeated identifiers, indicating a negative effect of specific stimulus information on processing rule information. Application of a network model to the 2 experiments, which provided for the growth of connections between attribute values in learning, indicated that repetition of identifiers produced a unitizing effect on stimuli. Results suggested that unitization produced interference through connections between irrelevant attribute values.

Relationship between 'on-treatment platelet reactivity', shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

BACKGROUND: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. METHODS: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. DISCUSSION: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

GaAs Clusters in the Quantum Size Regime: Growth on High Surface Area Silica by Molecular Beam Epitaxy.

Molecular beam epitaxy has been used to grow microcrystalline clusters of gallium arsenide (GaAs) in the size range from 2.5 to 60 nanometers on high-purity, amorphous silica supports. High-resolution transmission electron microscopy reveals that clusters as small as 3.5 nanometers have good crystalline order with a lattice constant equal to that of bulk GaAs. Study of the microcrystallite surfaces by x-ray photoelectron spectroscopy shows that they are covered with a shell (1.0 to 1.5 nanometers thick) of native oxides of gallium and arsenic (Ga(2)O(3) and As(2)O(3)), whose presence could explain the low luminescence efficiency of the clusters. Optical absorption spectra of the supported GaAs are consistent with the blue-shifted band edge expected for semiconductor microcrystallites in the quantum size regime.

Diagnostic hypothesis generation and human judgment.

Diagnostic hypothesis-generation processes are ubiquitous in human reasoning. For example, clinicians generate disease hypotheses to explain symptoms and help guide treatment, auditors generate hypotheses for identifying sources of accounting errors, and laypeople generate hypotheses to explain patterns of information (i.e., data) in the environment. The authors introduce a general model of human judgment aimed at describing how people generate hypotheses from memory and how these hypotheses serve as the basis of probability judgment and hypothesis testing. In 3 simulation studies, the authors illustrate the properties of the model, as well as its applicability to explaining several common findings in judgment and decision making, including how errors and biases in hypothesis generation can cascade into errors and biases in judgment.

Patient safety ward round checklist via an electronic app: implications for harm prevention.

INTRODUCTION: Patient safety is a value at the core of modern healthcare. Though awareness in the medical community is growing, implementing systematic approaches similar to those used in other high reliability industries is proving difficult. The aim of this research was twofold, to establish a baseline for patient safety practices on routine ward rounds and to test the feasibility of implementing an electronic patient safety checklist application. METHODS: Two research teams were formed; one auditing a medical team to establish a procedural baseline of "usual care" practice and an intervention team concurrently was enforcing the implementation of the checklist. The checklist was comprised of eight standard clinical practice items. The program was conducted over a 2-week period and 1 month later, a retrospective analysis of patient charts was conducted using a global trigger tool to determine variance between the experimental groups. Finally, feedback from the physician participants was considered. RESULTS: The results demonstrated a statistically significant difference on five variables of a total of 16. The auditing team observed low adherence to patient identification (0.0%), hand decontamination (5.5%), and presence of nurse on ward rounds (6.8%). Physician feedback was generally positive. CONCLUSIONS: The baseline audit demonstrated significant practice bias on daily ward rounds which tended to omit several key-proven patient safety practices such as prompting hand decontamination and obtaining up to date reports from nursing staff. Results of the intervention arm demonstrate the feasibility of using the Checklist App on daily ward rounds.

Thrombolysis for stroke in Ireland: increasing access and maintaining safety in a challenging environment.

BACKGROUND: In the setting of a national audit of acute stroke services, we examined the delivery of thrombolytic therapy for ischaemic stroke and whether current practice was achieving safe outcomes and consistent delivery for patients. METHOD: Data obtained from the recent national stroke audit was compared against previous Irish audit, the most recent SSNAP UK stroke audit and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) study. RESULTS: Thrombolysis was provided in 27 acute hospitals throughout Ireland during the period assessed with 82% (22/27) providing 24/7 access, the remaining sites using redirect policies. Decision to thrombolyse was made by stroke trained consultants in 63% (17/27) of units, with general physicians and emergency medicine consultants covering the other units. Thrombolysis rate for non-haemorrhagic stroke was 11% (n = 80/742, CI 95% ±2.23) versus a 1% rate in the 2008 audit. Sites receiving patients through a redirect policy had the highest thrombolysis rate, an average of 24%. Nearly 30% of cases were thrombolysed on the weekend. Eighty-three percent of cases were managed in a stroke unit at some time during admission versus 54% of the national total cases. Thirty-seven percent of patients were ≥80 years old. The mortality rate was 11.3% versus the national mortality rate for non-thrombolysed ischaemic strokes of 10% (p > 0.5), and this is comparable to the SITS-MOST 2007 study 3-month mortality rate of 11.3% (p > 0.5). CONCLUSION: Stroke thrombolysis is being effectively and safely provided in acute stroke services in Ireland despite regular involvement of non-specialist staff. There is still potential to improve thrombolysis rate.

The under use of thromboprophylaxis in older medical in-patients: a regional audit.

BACKGROUND: The risk of venous thromboembolism (VTE) among medical in-patients increases with age. Thromboprophylaxis using low-molecular-weight heparin can reduce the incidence by 50%, but anecdotally is under-used in medical patients, particularly the elderly. AIM: To examine prescribing practice for thromboprophylaxis in elderly in-patients in the Yorkshire region. DESIGN: Regional audit of medical records and drug charts. METHODS: A simultaneous audit was done of all medical in-patients >75 years on 30 wards in 10 hospitals. Guidelines published by the Scottish Intercollegiate Guidelines Network (SIGN) on the use of thromboprophylaxis were used as the standard. Data were collected on contraindications and/or indications for thromboprophylaxis and the type of prophylaxis used. RESULTS: Of 601 patients studied (mean age 84.6 years), 117 (19.5%) had indications for thromboprophylaxis with no contraindications. Of these 117, 34 (29%) were receiving prophylaxis as per guidelines. There was more than one indication for thromboprophylaxis in 17% of those left untreated. The mean age of those receiving therapy was similar to those not receiving it (84.0 vs. 84.5 years, p = 0.66, t-test). Elderly in-patients on medical wards were more likely to receive appropriate treatment than those on geriatric wards (43% vs. 23%, p = 0.03, chi(2) test). DISCUSSION: Thromboprophylaxis is under-used in older medical in-patients, despite their increased risk of VTE, particularly on geriatric wards. Greater consideration by doctors attending to older medical patients is needed if VTE is to be prevented.

Motivated to retrieve: how often are you willing to go back to the well when the well is dry?

Despite the necessity of the decision to terminate memory search in many real-world memory tasks, little experimental work has investigated the underlying processes. In this study, the authors investigated termination decisions in free recall by providing participants an open-ended retrieval interval and requiring them to press a stop button when they had finished retrieving. Three variables important to assessing one's willingness to search memory were examined: (a) the time spent searching memory after the last successful retrieval before choosing to quit (the exit latency); (b) task difficulty; and (c) individual differences in motivation, as measured by Webster and Kruglanski's (1994) Need for Closure Scale. A strong negative correlation was found between individual differences in motivation and participants' exit latencies. This negative correlation was present only when the retrieval task started out as relatively difficult.