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Aims Hyperaemic and non-hyperaemic pressure ratios (NHPR) are routinely used to identify significant coronary lesions. Machine learning (ML) techniques may help better understand these indices and guide future practice. This study assessed the ability of a purpose-built ML algorithm to classify coronary ischaemia during non-hyperaemia compared with the existing gold-standard technique (fractional flow reserve, FFR). Further, it investigated whether ML could identify components of coronary and aortic pressure cycles indicative of ischaemia. Methods and results Seventy-seven coronary vessel lesions (39 FFR defined ischaemia, 53 patients) with proximal and distal non-hyperaemic pressure waveforms and FFR values were assessed using supervised and unsupervised learning techniques in combination with principal component analysis (PCA). Fractional flow reserve measurements were obtained from the right coronary artery (13), left anterior descending (46), left circumflex (11), left main (1), obtuse marginal (2), and diagonal (4). The most accurate supervised learning classification utilized whole-cycle aortic with diastolic distal blood pressure waveforms, yielding a classification accuracy of 86.9% (sensitivity 86.8%, specificity 87.2%, positive predictive value 86.8%, negative predictive value 87.2%). Principal component analysis showed subtle variations in coronary pressures at the start of diastole have significant relation to ischaemia, and whole-cycle aortic pressure data are important for determining ischaemia. Conclusions Our ML algorithm classifies significant coronary lesions with accuracy similar to previous studies comparing time-domain NHPRs with FFR. Further, it has identified characteristics of pressure waveforms that relate to function. These results provide an application of ML to ischaemia requiring only standard data from non-hyperaemic pressure measurements.

Introduction: The head impulse test (HIT) and HIT combined with direction-changing Nystagmus-Test of Skew deviation (HINTS) have been proposed as bedside tests to differentiate between peripheral and central causes of vertigo in the emergency department (ED). We conducted a meta-analysis of the HIT and HINTS tests to diagnose peripheral vertigo (PV) and central vertigo. Methods: Pubmed, Google Scholar, EmBase, and articles references published in English up to July 2021 were searched for keywords “vertigo” or “acute vestibular syndrome” or “dizziness” and “head impulse” and “stroke.” The bivariate method for meta-analysis was used to calculate positive (PLR) and negative likelihood ratios (NLR) and summary receiver operating characteristics area under the curve (AUC). Results: A total of 11 studies were included analysing both HIT (8 studies, N = 417) and HINTS (6 studies, N = 405). HIT and HINTS were performed within 24 h in 4 of 11 studies. PLR and NLR for HIT in PV was 4.85 (95% CI: 2.83–8.08) and 0.19 (95% CI: 0.12–0.29, I2 63.25%), respectively. The AUC for HIT the diagnosis of PV and stroke was 0.90 and 0.92, respectively. PLR and NLR for a negative HIT in stroke was 5.85 (95% CI: 3.07–10.6) and 0.17 (95% CI: 0.08–0.30), respectively. PLR and NLR for peripheral HINTS pattern for PV was 17.3 (95% CI: 8.38–32.1) and 0.15 (95% CI: 0.07–0.26), respectively. PLR and NLR for central HINTS pattern for stroke: 5.61 (95% CI: 4.19–7.7) and 0.06 (95% CI: 0.03–0.12). In all included studies, HIT and HINTS exams were administered by neurology residents or neurology specialists with additional neuro-otology or neuro-ophthalmology subspeciality experience, and two studies included ED physicians. Raters reported high degree of bias and high concern regarding applicability in most domains of the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. Meta-regression did not demonstrate a statistically significant effect of publication year, time to test, and type of assessor on sensitivity or false positive rate. Conclusion: The HIT and HINTS exams appear to be moderately good discriminators of central and PV. However, in most papers, the tests were administered by neurologists and were evaluated beyond 24 h, which may limit utility in the ED setting.

BackgroundWe proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial.MethodsThe design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2–8 × 106/kg, i.v.) on preventing immunosuppression after stroke.ResultsEight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload.ConclusionOur Phase I trial demonstrates that a maximal dose of 2 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial.Clinical trial registrationClinicalTrials.gov, identifier ACTRN12618000076279P.

Background and ObjectivesA misdiagnosis of psychogenic nonepileptic seizures (PNES) and epileptic seizures (ES) is common. In the absence of the diagnostic gold standard (video EEG), clinicians rely on semiology and clinical assessment. However, questions regarding the diagnostic accuracy of different signs remain. This meta-analysis aimed to evaluate the diagnostic accuracy of semiology in PNES and ES.MethodsWe systematically searched PubMed, PsycInfo, and Medline for original research publications published before 8 February 2021 with no restriction on search dates to identify studies that compared semiology in ES and PNES in epilepsy monitoring units. Non-English publications, review articles, studies reporting on only PNES or ES, and studies limited to patients with developmental delay were excluded. Study characteristics and proportions of event groups and patient groups demonstrating signs were extracted from each article. A bivariate analysis was conducted, and data were pooled in a random effects model for meta-analysis. The I2 statistic was calculated to assess statistical heterogeneity. The revised Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the risk of bias in included studies. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were calculated. A PLR >10 or an NLR ResultsThe meta-analysis included 14 studies comprising 800 patients with ES and 452 patients with PNES. For PNES, ictal eye closure (PLR 40.5 95% confidence interval [CI] 16.2–101.3; I2 = 0, from 3 studies) and asynchronous limb movements (PLR 10.2; 95% CI 2.8–37.7; I2 = 0, from 3 studies) reached a PLR threshold >5. No single sign reached a PLR threshold >5 for ES.DiscussionWhile all signs require an interpretation in the overall clinical context, the presence of ictal eye closure and asynchronous limb movements are reliable discriminative signs for PNES.

Background and Purpose: Preclinical stroke studies endeavor to model the pathophysiology of clinical stroke, assessing a range of parameters of injury and impairment. However, poststroke pathology is complex and variable, and associations between diverse parameters may be difficult to identify within the usual small study designs that focus on infarct size. Methods: We have performed a retrospective large-scale big data analysis of records from 631 C57BL/6 mice of either sex in which the middle cerebral artery was occluded by 1 of 5 surgeons either transiently for 1 hour followed by 23-hour reperfusion (transient middle cerebral artery occlusion [MCAO]; n=435) or permanently for 24 hours without reperfusion (permanent MCAO; n=196). Analyses included a multivariate linear mixed model with random intercept for different surgeons as a random effect to reduce type I and type II errors and a generalized ordinal regression model for ordinal data when random effects are low. Results: Analyses indicated that brain edema volume was associated with infarct volume at 24 hours (β, 0.52 [95% CI, 0.45–0.59]) and was higher after permanent MCAO than after transient MCAO ( P Conclusions: Large-scale analysis of preclinical stroke data can provide researchers in our field with insight into relationships between variables not possible if individual studies are analyzed in isolation and has identified hypotheses for future study.

Introduction: Motor deficit is common following anterior cerebral artery (ACA) stroke. This study aimed to determine the impact on the motor outcome, given the location of descending corticofugal fiber tracts (from the primary motor cortex [M1], dorsal and ventral premotor area [PMdv], and supplementary motor area [SMA]) and the regional variations in collateral support of the ACA territory. Methods: Patients with ACA vessel occlusion were included. Disruption to corticofugal fibers was inferred by overlap of tracts with a lesion on computed tomography perfusion at the onset and on magnetic resonance imaging (MRI) poststroke. The motor outcome was defined by dichotomized and combined National Institute of Health Stroke Scale (NIHSS) sub-scores for the arm and leg. Multivariate hierarchical partitioning was used to analyze the proportional contribution of the corticofugal fibers to the motor outcome. Results: Forty-seven patients with a median age of 77.5 (interquartile range 68.0–84.5) years were studied. At the stroke onset, 96% of patients showed evidence of motor deficit on the NIHSS, and the proportional contribution of the corticofugal fibers to motor deficit was M1-33%, SMA-33%, and PMdv-33%. By day 7, motor deficit was present in Conclusion: Improvements in the motor outcome seen in ACA stroke may be due to the relative sparing of M1 fiber tracts from infarction. This may occur as a consequence of the posterior location of M1 fiber tracts and the evolving topography of ACA stroke due to the compensatory capacity of leptomeningeal anastomoses.

Background and Purpose: The circle of Willis (CoW) and leptomeningeal anastomoses play an important role in transforming infarct topography following middle cerebral artery occlusion. Their role in infarct topography following anterior cerebral artery occlusion is not well understood. The aim of this study was to evaluate the role of the CoW and leptomeningeal anastomoses in modifying regional variation in infarct topography following occlusion of the anterior cerebral artery and its branches. Methods: Perfusion and magnetic resonance imaging of patients with anterior cerebral artery stroke and evidence of vessel occlusion were segmented and manually registered to standard brain template for voxel-wise comparison. Next, a computer model of the cerebral arteries was formulated as network of nodes connected by cylindrical pipes. The experiments included occlusion of successive branches of the anterior cerebral artery while the configurations of the CoW were varied. Results: Forty-seven patients with a median age of 77.5 years (interquartile range, 68.0–84.5 years) were studied. The regions with the highest probabilities of infarction were the superior frontal gyrus (probability =0.26) and anterior cingulate gyrus (probability =0.24). The regions around the posterior cingulate gyrus (probability =0.08), paracentral lobule (probability =0.05), precuneus and superior parietal lobule (probability =0.03) had a low probability of infarction. Following occlusions distal to the anterior communicating artery, the computer model demonstrated an increase in flow (>30%) in neighboring cortical arteries with leptomeningeal anastomoses. Conclusions: Traditionally the CoW has been regarded as the primary collateral system. However, our computer model shows that the CoW is only helpful in redirecting flow following proximal vessel occlusions (pre-anterior communicating artery). More important are leptomeningeal anastomoses, which play an essential role in distal vessel occlusions, influencing motor outcome by modifying the posterolateral extent of infarct topography.

Social media (YouTube) has been used to educate the public on stroke signs and the need to contact emergency hotline. We perform sentiment analysis to explore the emotional response to the 2006 North American and contrast this with the five Australian campaigns (2009-2015). The positive sentiment in the North American campaign provides insights for developing material for public health campaigns.

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

Background To examine the effect of frailty on cognitive decline independent of cerebral small vessel disease (cSVD) and brain atrophy, and whether associations between neuropathology and cognition differed depending on frailty status. Methods The Tasmanian Study of Cognition and Gait was a population-based longitudinal cohort study with data collected at 3 phases from 2005 to 2012. Participants aged 60–85 were randomly selected from the electoral roll. Various data were used to operationalize a 36-item frailty index (FI) at baseline. Brain MRI was undertaken to obtain baseline measures of neuropathology. A neuropsychological battery was used to assess cognition at each time point. Generalized linear mixed models were used to examine the effect of frailty and MRI measures on cognition over time. The associations between MRI measures and cognition were explored after stratifying the sample by baseline frailty status. All analyses were adjusted for age, sex, and education. Results A total of 385 participants were included at baseline. The mean age was 72.5 years (standard deviation [SD] 7.0), 44% were female (n = 171). In fully adjusted linear mixed models, frailty (FI × time β −0.001, 95% confidence interval [CI] −0.003, −0.001, p = .03) was associated with decline in global cognition, independent of brain atrophy, and cSVD. The association between cSVD and global cognition was significant only in those with low levels of frailty (p = .03). Conclusion These findings suggest that frailty is an important factor in early cognitive dysfunction, and measuring frailty may prove useful to help identify future risk of cognitive decline.

Objectives:It is unknown whether there are sex-related profiles of cardiometabolic health that contribute differently to age-related changes in brain health during midlife. We studied how latent classes of middle-aged individuals clustering by age, sex, menopause and cardiometabolic health were associated with brain structure and cognitive performance.Methods:Health, brain and abdominal magnetic resonance imaging (MRI) data from the UK Biobank cohort (men and women >40 years in the United Kingdom) were used. We applied latent class analysis to identify groups of individuals based on age, sex, menopausal status and cardiometabolic health. We examined associations of class membership with brain volumes (total brain [TBV], grey matter [GMV], white matter [WMV], hippocampal [HV], white matter hyperintensities [WMHV]) and cognitive performance.Results:Data were available for 36,420 individuals (mean age 64.9 years, 48.5% women). Eight latent classes differing in age, sex and cardiometabolic risk were identified. Class 1 (reference class) included individuals with the lowest probability of older age and cardiometabolic risk, and they had the most positive associations with cognitive function and brain volumes. In those aged >60, but not in those aged 50-60 years, the negative associations of age with TBV, GMV and WMV were greater in the class comprising healthier older women than classes comprising older men of varying cardiometabolic and vascular health. There were no age-class interactions for cognitive test performance.Conclusions:Latent class analysis detected groups of middle-aged individuals clustering by cardiometabolic health. The relationship of age with brain volumes varies by sex, menopausal status and cardiometabolic health profile.

BackgroundThere has been a decline in the stroke incidence across high income countries but such knowledge exists at Country or State rather than areal unit level such local government area (LGA). In this disease mapping study, we evaluate if there are local hot spots or temporal trends in TIA rate. Such knowledge will be of help in planning healthcare service delivery across regions.MethodsLinked hospital discharge data (Victorian Admitted Episodes Dataset or VAED) was used to collect TIA (defined by ICD-10-AM codes G450-G459) cases from 2001 to 2011. The State of Victoria is the second most populous state in Australia, with a population of 6.7 million and can be divided into 79 administrative units or LGA. The data is anonymized and contains residence of the patient in terms of LGA but not exact location. The date of the TIA event when the patient is admitted to hospital is provided in the dataset. The number of TIAs per year was aggregated for each LGA. Standardized TIA ratios were calculated by dividing actual over expected cases for each LGA per year. We used Integrated Nested Laplace Approximation (INLA) to perform spatial and spatiotemporal regression, adjusting for hypertension, sex and population, age (≥60), and socio-economic status (SES) decile within the LGA. The final model was chosen based on the lowest the Deviance Information Criterion (DIC) and Watanabe-Akaike information criteria (WAIC).ResultsChoropleth maps showed a higher standardized TIA ratios in North-West rural region. Compared to the baseline model (DIC 13,159, WAIC 13,261), adding in a spatial random effect significantly improved the model (DIC 6,463, WAIC 6,667). However, adding a temporal component did not lead to a significant improvement (DIC 6,483, WAIC 6,707).ConclusionOur finding suggests a statically significant spatial component to TIA rate over regional areas but no temporal changes or yearly trends. We propose that such exploratory method should be followed by evaluation of reasons for regional variations and which in turn can identify opportunities in primary prevention of stroke, and stroke care.

Stroke is responsible for almost 6 million deaths and more than 10% of all mortalities each year, and two-thirds of stroke survivors remain disabled. With treatments for ischemic stroke still limited to clot lysis and/or mechanical removal, new therapeutic targets are desperately needed. In this review, we provide an overview of the complex mechanisms of innate and adaptive immune cell-mediated inflammatory injury, that exacerbates infarct development for several days after stroke. We also highlight the features of poststroke systemic immunodepression that commonly leads to infections and some mortalities, and argue that safe and effective therapies will need to balance pro- and anti-inflammatory mechanisms in a time-sensitive manner, to maximize the likelihood of an improved long-term outcome.

Despite intracerebral haemorrhage causing 5% of deaths worldwide, few evidence-based therapeutic strategies other than stroke unit care exist. Tranexamic acid decreases haemorrhage in conditions such as acute trauma and menorrhoea. We aimed to assess whether tranexamic acid reduces intracerebral haemorrhage growth in patients with acute intracerebral haemorrhage.We did a prospective, double-blind, randomised, placebo-controlled, investigator-led, phase 2 trial at 13 stroke centres in Australia, Finland, and Taiwan. Patients were eligible if they were aged 18 years or older, had an acute intracerebral haemorrhage fulfilling clinical criteria (eg, Glasgow Coma Scale score of7, intracerebral haemorrhage volume70 mL, no identified or suspected secondary cause of intracerebral haemorrhage, no thrombotic events within the previous 12 months, no planned surgery in the next 24 h, and no use of anticoagulation), had contrast extravasation on CT angiography (the so-called spot sign), and were treatable within 4·5 h of symptom onset and within 1 h of CT angiography. Patients were randomly assigned (1:1) to receive either 1 g of intravenous tranexamic acid over 10 min followed by 1 g over 8 h or matching placebo, started within 4·5 h of symptom onset. Randomisation was done using a centralised web-based procedure with randomly permuted blocks of varying size. All patients, investigators, and staff involved in patient management were masked to treatment. The primary outcome was intracerebral haemorrhage growth (33% relative or6 mL absolute) at 24 h. The primary and safety analyses were done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT01702636).Between March 1, 2013, and Aug 13, 2019, we enrolled and randomly assigned 100 participants to the tranexamic acid group (n=50) or the placebo group (n=50). Median age was 71 years (IQR 57-79) and median intracerebral haemorrhage volume was 14·6 mL (7·9-32·7) at baseline. The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32-1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication.Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. Larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified.National Health and Medical Research Council, Royal Melbourne Hospital Foundation.

ObjectiveDysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with Amyotrophic Lateral Sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based Quantitative Susceptibility Mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a six-month period.MethodsIron concentration was investigated using magnetic resonance based -QSM in the primary motor cortex and the pre-motor area in thirteen limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and eleven age and sex-matched healthy controls. Nine ALS patients underwent follow-up scans at six months.ResultsSignificantly increased QSM was observed in the left posterior primary motor area (p = 0.02, Cohen’s d = 0.9) and right anterior primary motor area (p = 0.02, Cohen’s d = 0.92) in all individuals with limb-onset ALS compared to healthy controls. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to healthy controls. No significant change in QSM was observed at the six-month follow-up scans in the ALS patients.ConclusionsThe findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a radiological indicator in disease diagnosis, and in clinical trials in limb-onset ALS and its subtypes.HighlightsSerial measurement of QSM in the motor cortex in limb-onset ALS was performedQSM changes in the motor cortex in ALS sub-groups were investigatedHigher QSM was observed in the motor cortex in Lumbar ALS relative to controlsQSM is sensitive to iron dysregulation in the motor cortex in limb-onset ALS

BackgroundSmall unruptured intracranial aneurysms (UIAs) are considered to have low risk of rupture. The proportion of UIAs measuring 10 mm or less in size that rupture when selected for conservative management without repair is not well known. The aim of this study is to determine the proportion of UIAs that rupture by size threshold from ≤10 to ≤3 mm when selected for management without repair and to determine the level of precision and sources of heterogeneity in the rupture risk estimate.MethodsThis study was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42019121522). The Ovid MEDLINE, EMBASE, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched (inception to August 2020). Studies with longitudinal follow-up of patients with UIAs ( ≤10 mm to ≤3 mm) without endovascular or neurosurgical repair were eligible. We included studies, which provided details of aneurysm size and in which UIA rupture was reported as an outcome. The primary outcome of the pooled proportion of UIA rupture during follow-up was synthesized with random-effects meta-analysis; heterogeneity was explored using meta-regression.ResultsA total of 31 studies that included 13,800 UIAs ≤10 mm in size were eligible for data synthesis. The pooled proportion of ≤10 mm UIAs that ruptured when managed without repair was 1.1% (95% CI 0.8–1.5; I2 = 52.9%) over 3.7 years. Findings were consistent in sensitivity analyses at all the size stratified thresholds including ≤5 and ≤3 mm; rupture occurred in 1.0% (95% CI 0.8–1.3; I2 = 0%) of 7,280 ≤5 mm UIAs and 0.8% (95% CI 0.4–1.5; I2 = 0%) of 1,228 ≤3 mm UIAs managed without repair. In higher quality studies with lower risk of bias, rupture occurred in 1.8% (95% CI 1.5–2.0; I2 = 0%) over 3.9 years. In meta-regression, aneurysm size, shape, anatomical location, and exposure to prior subarachnoid hemorrhage were not identified as sources of heterogeneity.ConclusionFor every 1,000 UIAs that are 10 mm or less in size and selected for conservative management without repair, between 8 and 15 UIAs are estimated to rupture over 3.7 years. When stratified by size, these pooled rupture risk estimates are consistent and clinically applicable for ≤5 mm UIAs selected for management without repair.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42019121522.

Background We investigated whether blood pressure lowering for secondary prevention is associated with a reduction in recurrent stroke risk and/or a higher risk of adverse events in very elderly compared with younger trial participants. Methods and Results This is a random effects meta‐analysis of randomized controlled trials of blood pressure lowering for secondary stroke prevention to evaluate age‐stratified (2 =49%), and the magnitude of risk reduction did not differ by age subgroup (2 =0%), but there was an increased risk in those ≥80 years (RR, 2.17 [95% CI, 1.22], 3.86, I 2 =0%). No increase was observed in the risk of falls, syncope, study withdrawal, or falls in either age subgroup. Conclusions Very elderly people in secondary prevention trials of blood pressure lowering have an increased risk of hypotensive symptoms, but with no statistical increase in the risk of falls, syncope, or mortality. However, evidence is lacking for frail elderly with multiple comorbidities who may be more vulnerable to adverse effects of blood pressure lowering.

Background Focal brain lesions can lend insight into the causal neuroanatomical substrate of depression in the human brain. However, studies of lesion location have led to inconsistent results. Methods Five independent datasets with different lesion etiologies and measures of postlesion depression were collated (N = 461). Each 3-dimensional lesion location was mapped to a common brain atlas. We used voxel lesion symptom mapping to test for associations between depression and lesion locations. Next, we computed the network of regions functionally connected to each lesion location using a large normative connectome dataset (N = 1000). We used these lesion network maps to test for associations between depression and connected brain circuits. Reproducibility was assessed using a rigorous leave-one-dataset-out validation. Finally, we tested whether lesion locations associated with depression fell within the same circuit as brain stimulation sites that were effective for improving poststroke depression. Results Lesion locations associated with depression were highly heterogeneous, and no single brain region was consistently implicated. However, these same lesion locations mapped to a connected brain circuit, centered on the left dorsolateral prefrontal cortex. Results were robust to leave-one-dataset-out cross-validation. Finally, our depression circuit derived from brain lesions aligned with brain stimulation sites that were effective for improving poststroke depression. Conclusions Lesion locations associated with depression fail to map to a specific brain region but do map to a specific brain circuit. This circuit may have prognostic utility in identifying patients at risk for poststroke depression and therapeutic utility in refining brain stimulation targets.

Background and Purpose— The computed tomography angiographic spot sign refers to contrast leakage within intracerebral hemorrhage (ICH). It has been proposed as a surrogate radiological marker for ICH growth. We conducted a meta-analysis to study the accuracy of the spot sign for predicting ICH growth and mortality. Methods— PubMed, Medline, conference proceedings, and article references in English up to June 2017 were searched for studies reporting “computed tomography angiography” and “spot sign” or “intracerebral hemorrhage” and “spot sign.” Each study was ranked on 27 criteria resulting in a quality rating score. Bivariate random effect meta-analysis was used to calculate positive and negative likelihood ratios and area under summary receiver operating characteristics curve for ICH growth and mortality. Hematoma growth was defined using the change in ≥6 mL or ≥33% increase in volume. Results— There were 26 studies describing 5085 patients, including 15 studies not used in previous meta-analyses. Positive likelihood ratio and negative likelihood ratio for ICH growth were 4.85 (95% CI, 3.85–6.02; I 2 =76.1%) and 0.49 (95% CI, 0.40–0.58) and mortality were 4.65 (95% CI, 3.67–5.90) and 0.55 (95% CI, 0.40–0.69), respectively. For ICH growth, the pooled sensitivity was 0.57 (95% CI, 0.49–0.64) and pooled false positive rate was 0.12 (95% CI, 0.09–0.14). The post-test probability of ICH growth was 0.57. The area under the curve for ICH growth and mortality was 0.86 and 0.87 (CIs are not provided in bivariate method). Meta-regression showed sensitivity of the test to decline significantly with subsequent year of publication (β=−0.148; 95% CI, −0.295 to −0.001; P =0.05). Higher quality assessment is associated with lower false positive rate (β=−0.074; 95% CI, −0.126 to −0.022; P =0.006). Conclusions— The high area under the curve potentially suggests that the spot sign can predict hematoma growth and mortality. Caution is recommended in its application given the heterogeneity across studies, which is appropriate given the data.

Nasogastric tube (NGT) is often used in stroke patients who are dysphagic (deglutition disorders) or have decreased conscious state. This method of feeding is assumed to have minimal complications. The aim of this study is to analyze complications associated with NGT and variables associated with mortality. Retrospective analysis of 250 acute stroke patients requiring NGT feeding between 2003 and 2020. There were 250 patients (median age 76 (IQR 68–83), 56.4% males, median time to NGT 1 day (IQR 0–3). Discussion with family prior to insertion of NGT recorded in 46 (18.4%). There were 123 cases (49.2%) of aspiration pneumonia. There were 188 (75.2%) NGT associated complications: 67 patients (26.8%) had failed insertion, 31 required multiple attempts, 129 patients (51.6%) pulled out NGT, 107 patients (42.8%) had NGT placed in wrong positions and require reinsertion, 20 cases in the lung, 5 pneumothorax cases, 97 in the gastro oesophageal junction or hiatus hernias, 1 case of oesophageal ulceration, 37 coiled, kinked or resistance. 78 cases the tips were not seen on chest X-ray (CXR), gastrointestinal bleeding in 9 cases, epistaxis in 6 cases), 96 patients (38.4%) required restrain. There were 91 death (36.4%) with 73 patients occurring during hospital admission and a further 18 died within 6 months. Death was more frequent in those age > 60 (72 of 216 patients versus 1 of 33 patients, p p 59, p = 0.03), NIHSS (≤ 16 or > 16, p = 0.02), post-stroke pneumonia (p = 0.04) and multiple NGT insertion (p = 0.01). The area under the ROC curve was for this model was 0.75 (95% CI 0.69–0.80). Complications were common among patients with NGT complications. These findings may be used to inform discussions with families regarding NGT.

Background: There is emphasis on timely administration of thrombolysis and clot retrieval but not antithrombotic therapy within 48 h for ischemic stroke (frequency of 64% in Australia and 97% in North America). We planned to assess the time metrics and variables associated with delaying antithrombotics (antiplatelet and anticoagulant therapy) administration.Methods: This was a retrospective study at Monash Health over 12 months in 2015. We plotted the cumulative event and mapped the key drivers (dimensionless variable Shapley value/SV) of antithrombotics.Results: There were 42 patients with transient ischemic attack/TIA and 483 with ischemic stroke [mean age was 71.8 ± 15.4; 56.0% male; nil by mouth (NBM) 74.5 and 49.3% of patients received “stat” (immediate and one off) dose antithrombotics]. The median time to imaging for the patients who did not have stroke code activated was 2.3 h (IQR 1.4–3.7), from imaging to dysphagia screen was 14.6 h (IQR 6.2–20.3), and from stopping NBM to antithrombotics was 1.7 h (IQR 0–16.5). TIA patients received antithrombotics earlier than those with ischemic stroke (90.5 vs. 86.5%, p = 0.01). Significant variables in regression analysis for time to antithrombotics were time to dysphagia screen (β 0.20 ± 0.03, SV = 3.2), nasogastric tube (β 19.8 ± 5.9, SV = −0.20), Alteplase (β 8.6 ± 3.6, SV = −1.9), stat dose antithrombotic (β −18.9 ± 2.9, SV = −10.8) and stroke code (β −5.9 ± 2.5, SV = 2.8). The partial correlation network showed that the time to antithrombotics increased with delay in dysphagia screen (coefficient = 0.33) and decreased if “stat” dose of antithrombotics was given (coefficient = −0.32).Conclusion: The proportion of patients receiving antithrombotics within 48 h was higher than previously reported in Australia but remained lower than the standard achieved in North American hospitals. Our process map and network analysis show avenues to shorten the time to antithrombotic.

OBJECTIVE The natural history of patients with stroke and cancer remains poorly understood in the modern era of hyper-acute stroke therapies (recombinant tissue plasminogen activator (tPA) and endovascular clot retrieval (ECR)). Prior to these advances in stroke treatment, a highly cited study reported median overall survival (mOS) 4.5 months after stroke in a cohort of patients with cancer (2004, n=96). Our aim is to evaluate outcome following stroke for patients with cancer in this modern era. Our hypothesis is that patients with stroke and cancer have better outcome than in earlier studies. DESIGN AND SETTING Retrospective analysis of admission to a tertiary Stroke Unit between January 2015 and September 2017 (N=1910), evaluation of hospital records and cancer treatment records. OUTCOME MEASURES Cancer was categorised as early stage (stage I and II) and advanced stage (stage III or IV, using the RD-Staging system). Survival analysis was performed in R. RESULTS There were 143 stroke patients with cancer (62% male) with mean age 73.2 +/- 12.5 years. Ischemic stroke occurred in 74.1% and 45 of 106 patients (42.5%) received intravenous thrombolysis (34/45) and / or endovascular clot retrieval (11/45). One patient who received ECR died within 30-days of stroke. Those with early-stage disease had mOS of 19.6 months (IQR 3.1, 31.5 months) and in advanced stage cancer mOS was 2.5 months (IQR 0.4, 6.3 months, p

Background and Purpose: Severity-based assessment tools may assist in prehospital triage of patients to comprehensive stroke centers (CSCs) for endovascular thrombectomy (EVT), but criticisms regarding diagnostic inaccuracy have not been adequately addressed. This study aimed to quantify the benefits and disadvantages of severity-based triage in a large real-world paramedic validation of the Ambulance Clinical Triage for Acute Stroke Treatment (ACT-FAST) algorithm. Methods: Ambulance Victoria paramedics assessed the prehospital ACT-FAST algorithm in patients with suspected stroke from November 2017 to July 2019 following an 8-minute training video. All patients were transported to the nearest stroke center as per current guidelines. ACT-FAST diagnostic accuracy was compared with hospital imaging for the presence of large vessel occlusion (LVO) and need for CSC-level care (LVO, intracranial hemorrhage, and tumor). Patient-level time saving to EVT was modeled using a validated Google Maps algorithm. Disadvantages of CSC bypass examined potential thrombolysis delays in non-LVO infarcts, proportion of patients with false-negative EVT, and CSC overburdening. Results: Of 517 prehospital assessments, 168/517 (32.5%) were ACT-FAST positive and 132/517 (25.5%) had LVO. ACT-FAST sensitivity and specificity for LVO was 75.8% and 81.8%, respectively. Positive predictive value was 58.8% for LVO and 80.0% when intracranial hemorrhage and tumor (CSC-level care) were included. Within the metropolitan region, 29/55 (52.7%) of ACT-FAST-positive patients requiring EVT underwent a secondary interhospital transfer. Prehospital bypass with avoidance of secondary transfers was modeled to save 52 minutes (95% CI, 40.0–61.5) to EVT commencement. ACT-FAST was false-positive in 8 patients receiving thrombolysis (8.1% of 99 non-LVO infarcts) and false-negative in 4 patients with EVT requiring secondary transfer (5.4% of 74 EVT cases). CSC bypass was estimated to over-triage 1.1 patients-per-CSC-per-week in our region. Conclusions: The overall benefits of an ACT-FAST algorithm bypass strategy in expediting EVT and avoiding secondary transfers are estimated to substantially outweigh the disadvantages of potentially delayed thrombolysis and over-triage, with only a small proportion of EVT patients missed.

Introduction and PurposeChronic Disease Management (CDM) plans are used by general practitioners to manage chronic diseases such as stroke. However, there is limited evidence that being on these plans improve adherence to secondary prevention medications after stroke. We aimed to assess the association of the duration on a CDM plan in improving adherence to secondary prevention medications following stroke. MethodsAustralian survivors of stroke or transient ischaemic attack were participants from the STAND FIRM trial. Patients were individually linked with claims for CDM plans from Medicare and dispensings of secondary prevention medications from the Pharmaceutical Benefits Scheme. We estimated (1) duration on a CDM plan based on the timing and Medicare items claimed and (2) the proportion of days that patients would have been covered by these medications (PDC), while accounting for deaths and instances of over-supply. Dosage for each quantity of medication was determined by the regularity in which patients returned for a refill. Logistic regression was used to evaluate factors associated with ≥80% adherence, up to 3 years after stroke, for each of antihypertensive, antithrombotic and lipid-modifying drugs. ResultsThe median PDC for 563 patients (median age 70yrs; 36% female) ranged from 92% to 95% among the three classes of medications. Approximately 27% did not take up a CDM plan, 33% were on plans for

IntroductionEpileptic and psychogenic non-epileptic seizures (PNES) are common diagnostic problems encountered in hospital practice. This study explores the use of unsupervised machine learning in discovering themes in medical records of patients presenting with PNES. We hypothesised that themes generated by machine learning are comparable with the classification by human experts.MethodsThis is a retrospective analysis of the medical records in the emergency department of patients (age >18 years) with PNES who underwent inpatient video-electroencephalography monitoring from May 2009 to June 2014 and received a final diagnosis of PNES. Prior to machine learning of written text, we applied a standardised approach in natural language processing to create a document-term matrix (removal of numbers, stop-words and punctuations, transforming fonts to lower case). The words were separated into tokens and treated as if existing within a bag-of-words. A probability of each word existing within a topic (theme) was modelled on multivariate Dirichlet distribution (R Foundation, V.3.5.0). Next, we asked four experts to independently provide a clinical interpretation of the generated topics. When the majority of (≥3) experts agreed, it was regarded as highly congruent. Interactive data are available on the web at (https://gntem2.github.io/PNES/%23topic=1&lambda=0.6&term=).ResultsThere were 39 patients (74.4% women, median age 35 years with range 20–82). A total of 121 documents were converted to text files for text mining. There were 15 generated topics with 12/15 topics rated as highly congruent. The main themes were about descriptors of seizures and medication use.ConclusionsThe findings from machine learning on PNES-related documentation provides evidence for the feasibility of applying machine-learning methodology to analyse large volumes of medical records. The topics generated by machine learning were congruent with interpretations by clinicians indicating this method can be used for screening of medical conditions among large volumes of medical records.

Problem Currently Background In Australia there are very few options for women to access public funded homebirth. Aim We aimed to use geo-mapping to identify the number of women eligible for homebirth in Victoria, based on the criteria of uncomplicated pregnancies and residing within 15–25 kms of suitable maternity services, to plan future maternity care options. Methods Retrospective study of births between 2015 and 2017 in Victoria, Australia. All women who were identified as having a low risk pregnancy at the beginning of pregnancy were included. The number of women within 15 and 25 km of a suitable Victorian public maternity hospital and catchment boundaries around each hospital were determined. Findings Between 2015 and 2017, 126,830 low risk women gave birth in Victoria, of whom half live within 25 km of seven Victorian hospitals. Currently, 2% of suitable women who live close to the current public homebirth models accessed them. Discussion We present a method to inform the expansion of maternity service options using Victoria as an example. On the basis of the maximum number of low risk women living close by, we have also identified the Victorian maternity services that would be most suitable for creation of public homebirth or low risk continuity of midwifery models. Conclusion This approach could can be used to plan other maternity care services.

BackgroundThe emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran.MethodsThis study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model.ResultsDuring the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p&nbsp

Background and PurposeThe novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic.MethodsThis is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center.ConclusionThe proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.

Highlights • Globally, there was a significant correlation between healthy life expectancy (HALE), non-communicable disease DALYs and mortality, with COVID-19 caseload and deaths. • There was a positive independent association between HALE and COVID-19 cases. • The number of tourists was also associated with COVID-19 mortality. • Our integrated model of global data is valuable for health policymakers, allowing for the implementation of optimal preventative measures at national and global scales., Background The interaction between coronavirus disease 2019 (COVID-19) and non-communicable diseases may increase the global burden of disease. We assessed the association of COVID-19 with ageing and non-communicable diseases. Methods We extracted data regarding non-communicable disease, particularly cardiovascular disease, deaths, disability-adjusted life years (DALYs), and healthy life expectancy (HALE) from the Global Burden of Disease Study (GBD) 2017. We obtained data of confirmed COVID-19 cases, deaths, and tests from the Our World in Data database as of May 28, 2020. Potential confounders of pandemic outcomes analyzed include institutional lockdown delay, hemispheric geographical location, and number of tourists. We compared all countries according to GBD classification and World Bank income level. We assessed the correlation between independent variables associated with COVID-19 caseload and mortality using Spearman's rank correlation and adjusted mixed model analysis. Findings High-income had the highest, and the Southeast Asia, East Asia, and Oceania region had the least cases per million population (3050.60 vs. 63.86). Sub-saharan region has reported the lowest number of COVID-19 mortality (1.9). Median delay to lockdown initiation varied from one day following the first case in Latin America and Caribbean region, to 34 days in Southeast Asia, East Asia, and Oceania. Globally, non-communicable disease DALYs were correlated with COVID-19 cases (r = 0.32, p

Objectives Age and female sex are risk factors for dementia, and menopause is associated with cognitive dysfunction. Previous work largely considered the effects of sex and menopause as being independent of age. We studied whether age interacts with sex or menopause in explaining imaging biomarkers of dementia during midlife. Methods In this cross-sectional study of UK Biobank participants with brain magnetic resonance imaging (MRI), we explored the interaction of age with sex or menopausal status in explaining total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), white matter hyperintensity volume (WMHV), regional cortical volume , and subcortical volume. Results Data were available for 1827 postmenopausal women, 230 pre/perimenopausal women and 2165 men (median age 63.3 years). There was a significant interaction between age and sex (P = .024) for TBV, where the inverse association age with TBV was steeper in women (β = –5.35 mL/year) than in men (β = –4.77 mL/year). Similar age–sex interactions were also observed for GMV and WMV. In women, there was a significant interaction between age and menopausal status (P = .007) where the inverse association of age with TBV was steeper in postmenopausal (β = –5.89 mL/year) than in pre/perimenopausal women (β = –1.61 mL/year). Similar age–menopause interactions were found in predicting lower GMV and higher WMHV. Differences in the direction of these age–sex and age–menopause interactions were found for regional cortical and subcortical brain volumes. Conclusion Sex and menopause both interact with age during midlife in explaining MRI biomarkers of dementia. Further work is required to understand the mechanisms driving these interactions to develop strategies for delaying dementia.