Pre-stroke anticoagulation for atrial fibrillation in primary English speakers and non-primary English speakers: a multicentre retrospective cohort study.

BACKGROUND: Anticoagulation can prevent most strokes in individuals with atrial fibrillation (AF); however, many people presenting with stroke and known AF are not anticoagulated. Language barriers and poor health literacy have previously been associated with decreased patient medication adherence. The association between language barriers and initiation of anticoagulation therapy for AF is uncertain. AIMS: The aims of this study were to determine whether demographic factors, including non-English primary language, were (1) associated with not being initiated on anticoagulation for known AF prior to admission with stroke, and (2) associated with non-adherence to anticoagulation in the setting of known AF prior to admission with stroke. METHODS: A multicentre retrospective cohort study was conducted for consecutive individuals admitted to the three South Australian tertiary hospitals with stroke units over a 5-year period. RESULTS: There were 6829 individuals admitted with stroke. These cases included 5835 ischaemic stroke patients, 1333 of whom had pre-existing AF. Only 40.0% presenting with ischaemic stroke in the setting of known pre-existing AF were anticoagulated. When controlling for demographics, socioeconomic status and past medical history (including the components of the CHADS2VASC score and anticoagulation contraindications), having a primary language other than English was associated with a lower likelihood of having been commenced on anticoagulant for known pre-stroke AF (odds ratio: 0.52, 95% confidence interval: 0.36-0.77, P = 0.001), but was not associated with a differing likelihood of anticoagulation adherence. CONCLUSIONS: A significant proportion of patients with stroke have pre-existing unanticoagulated AF; these rates are substantially higher if the primary language is other than English. Targeted research and interventions to minimise evidence-treatment gaps in this cohort may significantly reduce stroke burden.

Resuscitation orders demonstrate differences by gender, stroke type and intervention.

BACKGROUND AND PURPOSE: Resuscitation orders describe individual preferences and types of intervention, such as suitability for cardiopulmonary resuscitation (CPR), that may provide benefit in the event of critical deterioration. The purpose of this study was to examine stroke inpatient resuscitation order completion and content. METHODS: This retrospective cohort study examined resuscitation orders in consecutive individuals admitted to a tertiary stroke centre over a 21-month period. Multivariable logistic regression was used to identify factors associated with resuscitation order completion and content. RESULTS: 1924 individuals were included in the study. The proportion of individuals who had resuscitation orders completed was 37.4%. Several factors were associated with an increased likelihood of resuscitation order completion including having received endovascular thrombectomy (p=0.013) and having intracerebral haemorrhage (p=0.001). Females were more likely to have a resuscitation order that is not for CPR (p=0.021, OR 95%CI 1.080-2.542). Patients with intracerebral haemorrhage were also more likely to be not for CPR (p=0.037, OR 95%CI 1.039-3.353). CONCLUSIONS: Disparities exist in resuscitation order completion and content based on demographic and stroke characteristics. Further research is required to identify the reasons for these differences and to optimise resuscitation order completion.

Ultra-Long Transfers for Endovascular Thrombectomy-Mission Impossible?: The Australia-New Zealand Experience.

BACKGROUND: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0-2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. METHODS: This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). RESULTS: There were 131 patients; the median age was 64 [53-74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12-22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1-3] versus 3 [1-6] in the patients selected with noncontrast CT+CT angiography, P=0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01-0.19]; P<0.01). CONCLUSIONS: In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.

Factors associated with delay to carotid endarterectomy for acute ischaemic stroke in South Australia: A multicentre retrospective cohort study.

BACKGROUND: The greatest benefits of carotid endarterectomy (CEA) accrue when performed within two weeks of acute ischaemic stroke (AIS) due to symptomatic carotid stenosis. Previous studies have identified multiple factors contributing to CEA delay. AIMS: To determine factors associated with delayed CEA in patients admitted to tertiary stroke centres within a major metropolitan region with AIS METHODS: In a retrospective cohort study, consecutive patients admitted to the tertiary hospitals with stroke units within South Australia (Lyell McEwin Hospital, Royal Adelaide Hospital and Flinders Medical Centre) between 2016 to 2020 were included. Univariable and multivariable logistic regression were used to identify individual factors associated with time from symptom onset to CEA of over two weeks. RESULTS: A total of 174 patients were included. The median time to CEA was 5 days (IQR 3-9.75). Delayed CEA beyond 14 days occurred in 28/174 (16%). Factors most associated with delayed CEA included presentation to a tertiary hospital without onsite Vascular Surgical Unit (OR 3.71, 95%CI 1.31-10.58), history of previous stroke (OR 3.38, 95% CI 1.11-9.84) and presenting NIHSS above 6 (OR 5.16, 95% CI 1.60-16.39). CONCLUSION: This study identified that presentation to a tertiary hospital without a Vascular Surgery Unit, history of previous stroke and presenting NIHSS above 6 were associated with delay to CEA in AIS patients in South Australia. Interventional studies aiming to improve the proportion of patients that receive CEA within 14 days are required.

Implementation of the South Australian Regional Telestroke service is associated with improved care quality and lower stroke mortality: A retrospective cohort study.

INTRODUCTION: Stroke in Regional Australia may have worse outcomes due to difficulties accessing optimal care. The South Australian Regional Telestroke service aimed to improve telestroke neurologist access, supported by improved ambulance triage. OBJECTIVE: To assess stroke care quality and patient mortality pre- and postimplementation of a vascular neurologist-led Telestroke service. DESIGN: Historically controlled mixed methods cohort study comparing key quality indicators and patient mortality (6 months pre- vs. 18 months postimplementation date [4 June 2018]) at the three major South Australian regional stroke centres. The primary outcome was 13 care quality indicators as a combined composite risk-adjusted score, and the secondary outcome was risk-adjusted mortality at 12-month postadmission. FINDINGS: On an annualised basis, of 189 patients with stroke, more were admitted postintervention to the regional stroke centres than in the control period (158 [annualised rate 105.3, 95% CI 86.2-127.4] vs. 31 [annualised rate 62.0, 95% CI 47.5-79.5]) Baseline patient characteristics were similar in both periods. Post-implementation, median last-known-well time to presentation (3.5 h [IQR 1.6-17] vs. 2.0 [IQR 1-14]; p = 0.46) and door to needle times (121 min [IQR 97-144] vs. 90 [IQR 75-138]; p = 0.65) were not significantly lower but an improvement in the combined composite quality score was observed (0.069 [95% CI 0.004-0.134; p = 0.04]), reflecting individual improvements in some quality indicators. Mortality at 12-month postimplementation was substantially lower postimplementation (prechange 23% vs. postchange 13% [hazard ratio 0.58 (95% CI 0.44-0.76; p < 0.001)]). CONCLUSION: Implementation of a South Australian Regional Telestroke service was associated with improved care metrics and lower mortality.

Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke.

BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).

Automated information extraction from free-text medical documents for stroke key performance indicators: a pilot study.

Automated information extraction might be able to assist with the collection of stroke key performance indicators (KPI). The feasibility of using natural language processing for classification-based KPI and datetime field extraction was assessed. Using free-text discharge summaries, random forest models achieved high levels of performance in classification tasks (area under the receiver operator curve 0.95-1.00). The datetime field extraction method was successful in 29 of 43 (67.4%) cases. Further studies are indicated.

Machine learning in the prediction of medical inpatient length of stay.

Length of stay (LOS) estimates are important for patients, doctors and hospital administrators. However, making accurate estimates of LOS can be difficult for medical patients. This review was conducted with the aim of identifying and assessing previous studies on the application of machine learning to the prediction of total hospital inpatient LOS for medical patients. A review of machine learning in the prediction of total hospital LOS for medical inpatients was conducted using the databases PubMed, EMBASE and Web of Science. Of the 673 publications returned by the initial search, 21 articles met inclusion criteria. Of these articles the most commonly represented medical specialty was cardiology. Studies were also identified that had specifically evaluated machine learning LOS prediction in patients with diabetes and tuberculosis. The performance of the machine learning models in the identified studies varied significantly depending on factors including differing input datasets and different LOS thresholds and outcome metrics. Common methodological shortcomings included a lack of reporting of patient demographics and lack of reporting of clinical details of included patients. The variable performance reported by the studies identified in this review supports the need for further research of the utility of machine learning in the prediction of total inpatient LOS in medical patients. Future studies should follow and report a more standardised methodology to better assess performance and to allow replication and validation. In particular, prospective validation studies and studies assessing the clinical impact of such machine learning models would be beneficial.

Deep Learning Natural Language Processing Successfully Predicts the Cerebrovascular Cause of Transient Ischemic Attack-Like Presentations.

Background and Purpose- Triaging of referrals to transient ischemic attack (TIA) clinics is aided by risk stratification. Deep learning-based natural language processing, a type of machine learning, may be able to assist with the prediction of cerebrovascular cause of TIA-like presentations from free-text information. Methods- Consecutive TIA clinic notes were retrieved from existing databases. Texts associated with cerebrovascular and noncerebrovascular diagnoses were preprocessed before classification experiments, using a variety of classifier models, based on only the free-text description of the history of presenting complaint. The primary outcome was area under the curve (AUC) of the receiver operator curve. The model with the greatest AUC was then used in classification experiments in which it was provided with additional clinical information. Results- Of the classifier models trialed on the history of presenting complaint, the convolutional neural network achieved the greatest predictive capability (AUC±SD; 81.9±2.0). The effects of additional clinical information on AUC were variable. The greatest AUC was achieved when the convolutional neural network was provided with the history of presenting complaint and magnetic resonance imaging report (88.3±3.6). Conclusions- Deep learning-based natural language processing, in particular convolutional neural networks, based on medical free-text, may prove effective in prediction of the cause of TIA-like presentations. Future research investigating the role of the application of deep learning-based natural language processing to the automated triaging of clinic referrals in TIA, and potentially other specialty areas, is indicated.

Perfusion computed tomography in patients with stroke thrombolysis.

See Saver (doi:10.1093/awx020) for a scientific commentary on this article.Stroke shortens an individual's disability-free life. We aimed to assess the relative prognostic influence of pre- and post-treatment perfusion computed tomography imaging variables (e.g. ischaemic core and penumbral volumes) compared to standard clinical predictors (such as onset-to-treatment time) on long-term stroke disability in patients undergoing thrombolysis. We used data from a prospectively collected international, multicentre, observational registry of acute ischaemic stroke patients who had perfusion computed tomography and computed tomography angiography before treatment with intravenous alteplase. Baseline perfusion computed tomography and follow-up magnetic resonance imaging were analysed to derive the baseline penumbra volume, baseline ischaemic core volume, and penumbra salvaged from infarction. The primary outcome measure was the effect of imaging and clinical variables on Disability-Adjusted Life Year. Clinical variables were age, sex, National Institutes of Health Stroke Scale score, and onset-to-treatment time. Age, sex, country, and 3-month modified Rankin Scale were extracted from the registry to calculate disability-adjusted life-year due to stroke, such that 1 year of disability-adjusted life-year equates to 1 year of healthy life lost due to stroke. There were 772 patients receiving alteplase therapy. The number of disability-adjusted life-year days lost per 1 ml of baseline ischaemic core volume was 17.5 (95% confidence interval, 13.2-21.9 days, P < 0.001). For every millilitre of penumbra salvaged, 7.2 days of disability-adjusted life-year days were saved (ß = -7.2, 95% confidence interval, -10.4 to -4.1 days, P < 0.001). Each minute of earlier onset-to-treatment time resulted in a saving of 4.4 disability-free days after stroke (1.3-7.5 days, P = 0.006). However, after adjustment for imaging variables, onset-to-treatment time was not significantly associated with savings in disability-adjusted life-year days. Pretreatment perfusion computed tomography can (independently of clinical variables) predict significant gains, or loss, of disability-free life in patients undergoing reperfusion therapy for stroke. The effect of earlier treatment on disability-free life appears explained by salvage of penumbra, particularly when the ischaemic core is not too large.

Evaluation of a CTA-Triage Based Transient Ischemic Attack Service: A Retrospective Single Center Cohort Study.

OBJECTIVE: We designed a computed tomography angiography (CTA)-based algorithm for patients presenting to hospital with a transient ischemic attack (TIA) which identified high-risk patients, as well as inpatient versus semiurgent outpatient management following MRI, and we hypothesised that this would be effective. METHODS: Patients seen in the ED at the Royal Adelaide Hospital from March 3, 2012 to November 30, 2016 with TIA-like symptoms were assessed for a cardioembolic source (clinical assessment, electrocardiogram) and underwent intra and extracranial CTA. Patients with a referable >50% stenosis were admitted and given dual antiplatelets. Most high-risk cardiac source patients were also admitted and anticoagulated. Other patients were loaded with aspirin, or changed to clopidogrel if on aspirin, and reviewed as outpatients following semiurgent MRI (3-4 days). We assessed the 90-day recurrent stroke risk in this cohort as a whole, and in those with a final cerebrovascular diagnosis. RESULTS: 1167 patients were diagnosed in Emergency as TIA and referred via our algorithm. A total of 150 were admitted, 78 had "high-risk" features. A total of 1017 patients were reviewed in the TIA clinic. The average age of the total cohort was 65.8 years old. Final diagnosis was TIA/minor stroke in 69% admitted patients and 30% clinic patients (P value < .0001). The 90-day recurrent stroke risk in these patients was 2.0% (5.8% admitted vs .7% clinic patients, P value < .0001). In those with noncerebrovascular diagnoses, there were no recurrent strokes within 90 days. CONCLUSIONS: Stroke risk is very low using CTA guided semiurgent clinic review algorithm.

Validating a Predictive Model of Acute Advanced Imaging Biomarkers in Ischemic Stroke.

BACKGROUND AND PURPOSE: Advanced imaging to identify tissue pathophysiology may provide more accurate prognostication than the clinical measures used currently in stroke. This study aimed to derive and validate a predictive model for functional outcome based on acute clinical and advanced imaging measures. METHODS: A database of prospectively collected sub-4.5 hour patients with ischemic stroke being assessed for thrombolysis from 5 centers who had computed tomographic perfusion and computed tomographic angiography before a treatment decision was assessed. Individual variable cut points were derived from a classification and regression tree analysis. The optimal cut points for each assessment variable were then used in a backward logic regression to predict modified Rankin scale (mRS) score of 0 to 1 and 5 to 6. The variables remaining in the models were then assessed using a receiver operating characteristic curve analysis. RESULTS: Overall, 1519 patients were included in the study, 635 in the derivation cohort and 884 in the validation cohort. The model was highly accurate at predicting mRS score of 0 to 1 in all patients considered for thrombolysis therapy (area under the curve [AUC] 0.91), those who were treated (AUC 0.88) and those with recanalization (AUC 0.89). Next, the model was highly accurate at predicting mRS score of 5 to 6 in all patients considered for thrombolysis therapy (AUC 0.91), those who were treated (0.89) and those with recanalization (AUC 0.91). The odds ratio of thrombolysed patients who met the model criteria achieving mRS score of 0 to 1 was 17.89 (4.59-36.35, P<0.001) and for mRS score of 5 to 6 was 8.23 (2.57-26.97, P<0.001). CONCLUSIONS: This study has derived and validated a highly accurate model at predicting patient outcome after ischemic stroke.

Too good to treat? ischemic stroke patients with small computed tomography perfusion lesions may not benefit from thrombolysis.

OBJECTIVE: Although commonly used in clinical practice, there remains much uncertainty about whether perfusion computed tomography (CTP) should be used to select stroke patients for acute reperfusion therapy. In this study, we tested the hypothesis that a small acute perfusion lesion predicts good clinical outcome regardless of thrombolysis administration. METHODS: We used a prospectively collected cohort of acute ischemic stroke patients being assessed for treatment with IV-alteplase, who had CTP before a treatment decision. Volumetric CTP was retrospectively analyded to identify patients with a small perfusion lesion (<15ml in volume). The primary analysis was excellent 3-month outcome in patients with a small perfusion lesion who were treated with alteplase compared to those who were not treated. RESULTS: Of 1526 patients, 366 had a perfusion lesion <15ml and were clinically eligible for alteplase (212 being treated and 154 not treated). Median acute National Institutes of Health Stroke Scale score was 8 in each group. Of the 366 patients with a small perfusion lesion, 227 (62%) were modified Rankin Scale (mRS) 0 to 1 at day 90. Alteplase-treated patients were less likely to achieve 90-day mRS 0 to 1 (57%) than untreated patients (69%; relative risk [RR] = 0.83; 95% confidence interval [CI], 0.71-0.97; p = 0.022) and did not have different rates of mRS 0 to 2 (72% treated patients vs 77% untreated; RR, 0.93; 95% CI, 0.82-1.95; p = 0.23). INTERPRETATION: This large observational cohort suggests that a portion of ischemic stroke patients clinically eligible for alteplase therapy with a small perfusion lesion have a good natural history and may not benefit from treatment. Ann Neurol 2016;80:286-293.

Determining the Number of Ischemic Strokes Potentially Eligible for Endovascular Thrombectomy: A Population-Based Study.

BACKGROUND AND PURPOSE: Endovascular thrombectomy (ET) is standard-of-care for ischemic stroke patients with large vessel occlusion, but estimates of potentially eligible patients from population-based studies have not been published. Such data are urgently needed to rationally plan hyperacute services. Retrospective analysis determined the incidence of ET-eligible ischemic strokes in a comprehensive population-based stroke study (Adelaide, Australia 2009-2010). METHODS: Stroke patients were stratified via a prespecified eligibility algorithm derived from recent ET trials comprising stroke subtype, pathogenesis, severity, premorbid modified Rankin Score, presentation delay, large vessel occlusion, and target mismatch penumbra. Recognizing centers may interpret recent ET trials either loosely or rigidly; 2 eligibility algorithms were applied: restrictive (key criteria modified Rankin Scale score 0-1, presentation delay <3.5 hours, and target mismatch penumbra) and permissive (modified Rankin Scale score 0-3 and presentation delay <5 hours). RESULTS: In a population of 148 027 people, 318 strokes occurred in the 1-year study period (crude attack rate 215 [192-240] per 100 000 person-years). The number of ischemic strokes eligible by restrictive criteria was 17/258 (7%; 95% confidence intervals 4%-10%) and by permissive criteria, an additional 16 were identified, total 33/258 (13%; 95% confidence intervals 9%-18%). Two of 17 patients (and 6/33 permissive patients) had thrombolysis contraindications. Using the restrictive algorithm, there were 11 (95% confidence intervals 4-18) potential ET cases per 100 000 person-years or 22 (95% confidence intervals 13-31) using the permissive algorithm. CONCLUSIONS: In this cohort, ≈7% of ischemic strokes were potentially eligible for ET (13% with permissive criteria). In similar populations, the permissive criteria predict that ≤22 strokes per 100 000 person-years may be eligible for ET.

Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2.

BACKGROUND AND PURPOSE: Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years. METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls. RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2. CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.

Genetic overlap between diagnostic subtypes of ischemic stroke.

BACKGROUND AND PURPOSE: Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. METHODS: Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. RESULTS: High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10(-4)) and profile scores (rg=0.72; 95% confidence interval, 0.52-0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1×10(-7)) for single nucleotide polymorphisms near the opioid receptor µ1 (OPRM1) gene. CONCLUSIONS: Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes.

Safety of varenicline tartrate and counseling versus counseling alone for smoking cessation: a randomized controlled trial for inpatients (STOP study).

INTRODUCTION: Inpatient medical settings offer an opportunistic environment for initiating smoking cessation interventions to patients reflecting on their health. Current evidence has shown the superior efficacy of varenicline tartrate (VT) for smoking cessation compared with other tobacco cessation therapies; however, recent evidence also has highlighted concerns about the safety and tolerability of VT. Given these apprehensions, we aimed to evaluate the safety and effectiveness of VT plus quitline-counseling compared to quitline-counseling alone in the inpatient medical setting. METHODS: Adult patients (n = 392, 20-75 years) admitted with a smoking-related illnesses to 3 hospitals were randomized to receive either 12 weeks of varenicline tartrate (titrated from 0.5mg daily to 1mg twice daily) plus quitline-counseling (VT+C), (n = 196) or quitline-counseling alone (n = 196). RESULTS: VT was well tolerated in the inpatient setting among subjects admitted with acute smoking-related illnesses (mean age 52.8±2.89 and 53.7±2.77 years in the VT+C and counseling alone groups, respectively). The most common self-reported adverse event during the 12-week treatment phase was nausea (16.3% in the VT+C group compared with 1.5% in the counseling alone group). Thirteen deaths occurred during the study period (n = 6 were in the VT+C arm compared with n = 7 in the counseling alone arm). All of these subjects had known comorbidities or developed underlying comorbidities. CONCLUSIONS: VT appears to be a safe and well-tolerated opportunistic treatment for inpatient smokers who have related chronic disease. Based on the proven efficacy of varenicline from outpatient studies and our recent inpatient evidence, we suggest it be considered as part of standard care in the hospital setting.

Predictions for functional outcome and mortality in acute ischaemic stroke following successful endovascular thrombectomy.

Background: Accurate outcome predictions for patients who had ischaemic stroke with successful reperfusion after endovascular thrombectomy (EVT) may improve patient treatment and care. Our study developed prediction models for key clinical outcomes in patients with successful reperfusion following EVT in an Australian population. Methods: The study included all patients who had ischaemic stroke with occlusion in the proximal anterior cerebral circulation and successful reperfusion post-EVT over a 7-year period. Multivariable logistic regression and Cox regression models, incorporating bootstrap and multiple imputation techniques, were used to identify predictors and develop models for key clinical outcomes: 3-month poor functional status; 30-day, 1-year and 3-year mortality; survival time. Results: A total of 978 patients were included in the analyses. Predictors associated with one or more poor outcomes include: older age (ORs for every 5-year increase: 1.22-1.40), higher premorbid functional modified Rankin Scale (ORs: 1.31-1.75), higher baseline National Institutes of Health Stroke Scale (ORs: 1.05-1.07) score, higher blood glucose (ORs: 1.08-1.19), larger core volume (ORs for every 10 mL increase: 1.10-1.22), pre-EVT thrombolytic therapy (ORs: 0.44-0.56), history of heart failure (outcome: 30-day mortality, OR=1.87), interhospital transfer (ORs: 1.42 to 1.53), non-rural/regional stroke onset (outcome: functional dependency, OR=0.64), longer onset-to-groin puncture time (outcome: 3-year mortality, OR=1.08) and atherosclerosis-caused stroke (outcome: functional dependency, OR=1.68). The models using these predictors demonstrated moderate predictive abilities (area under the receiver operating characteristic curve range: 0.752-0.796). Conclusion: Our models using real-world predictors assessed at hospital admission showed satisfactory performance in predicting poor functional outcomes and short-term and long-term mortality for patients with successful reperfusion following EVT. These can be used to inform EVT treatment provision and consent.

Implementation of an optimised tele-medicine platform for stroke in South Australia improves patient care.

Background: Patients with a large vessel occlusion require a transfer from a primary stroke centre to access thrombectomy, often over significant distances in regional areas. We sought to optimise stroke care access in the regional South Australian Tele-Strokeservice (SATS) to improve patient access to thrombectomy. Methods: We undertook a 24-month interventional historically controlled cohort study comparing acute stroke care metrics in the SATS. This consisted of a 12-month control period and a 12-month intervention monitoring period. The study intervention considered of an education package provided to the regional hospitals, a stroke neurologist roster to receive consultations and the intervention of a centralised tele-stroke system to provide treatment advice and organise patient transfers where needed. The SATS services 61 rural hospitals in South Australia, and Alice Springs in the Northern Territory. Suspected acute stroke patients presenting to the participating regional hospitals in SATS network where a telehealth consultation took place. Results: Over the study period, there were 919 patient referrals, with 449 consultations in the pre-intervention phase and 470 in the post-intervention phase. Demographic features in both epochs were similar. The post-intervention phase was associated with shorter door-to-scan time (35 min, IQR: 18,70; vs. 49 min, IQR:25,102, p < 0.0001), faster door-to-thrombolysis time (58 min, IQR: 39,91, vs.83 min, IQR: 55,100, p = 0.0324) and a higher portion of patients treated with thrombectomy (54, 11.5% vs. 26, 5.8%, p = 0.002). Conclusion: An optimised implementation of a streamlined telehealth platform with ongoing education and feedback to referring sites was associated with improved stroke workflow metrics and higher thrombectomy rates.

Renal disease is not associated with delays in hyperacute stroke management in South Australia.

OBJECTIVE: The aims of the present study were to determine how renal disease is associated with the time to receive hyperacute stroke care. METHODS: The present study involved a 5-year cohort of all patients admitted to stroke units in South Australia. RESULTS: In those with pre-existing renal disease there were no significant differences in the time taken to receive a scan, thrombolysis or endovascular thrombectomy. CONCLUSIONS: The present study shows that in protocolised settings there were no significant delays in hyperacute stroke management for patients with renal disease.