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Governance can help in regulating the environmental quality of any economy. Hence, the present study explores the effects of rule of law and regulatory quality on the CO2 emissions in four South Asian economies from 1996-2019, controlling renewable energy and income level in the model. The results corroborate the Environmental Kuznets Curve (EKC) hypothesis in the long-run analysis of four South Asian economies but renewable energy could not affect the CO2 emissions. Moreover, regulatory quality helps reduce CO2 emissions and shows the technique and/or composition effects in these economies. However, the rule of law has a pre-dominant scale effect in these economies and increases CO2 emissions. Based on the results, we recommend South Asian countries to strengthen the regulatory quality to support a clean environment. Moreover, rule of law needs attention and modifications to have pleasant environmental effects.

Background: Cardiac complications may occur in patients following ischemic stroke (stroke-heart syndrome [SHS]). We investigated the mortality risk in patients with SHS and across the SHS manifestations., Methods and Results: Data were sought from the VISTA (Virtual International Stroke Trials Archive), an international repository of clinical trials data. We reviewed relevant adverse events and classified patients into 2 cohorts based on the incidence of SHS. The SHS was defined as developing any cardiac complications within 30 days following stroke. Using Cox proportional hazards models, we evaluated the temporal risk dynamics of 90-day death associated with the day of SHS onset. We also compared the risk of 90-day death across SHS manifestations, using multivariate analysis. Among 15 054 patients with ischemic stroke (mean age, 69±12 years; 55% men), 1787 (11.8% [95% CI, 11.3-12.3]) developed SHS. The median onset time for SHS was 2 (interquartile range, 1-4) days. The most prevalent manifestation was other arrhythmia/ECG abnormalities, with the incidence rate of 6.5% (95% CI, 6.1-6.9). Patients who developed SHS between 10 and 30 days following stroke had significantly higher risks of death compared with those with SHS within the first 0 to 3 days (adjusted hazard ratio, 1.84 [95% CI, 1.36-2.49]). In the multivariate-adjusted analysis, SHS manifested as acute myocardial injury/myocardial injury, heart failure/left ventricular dysfunction, and atrial fibrillation/flutter were associated with the highest risk of death within 90 days after stroke across SHS manifestations excluding cardiorespiratory arrest., Conclusions: SHS is associated with a high risk of death, with a greater risk observed with delayed SHS onset.

Background: The prediction of ischaemic stroke in patients with heart failure with reduced ejection fraction (HFrEF) but without atrial fibrillation (AF) remains challenging. Our aim was to evaluate the performance of machine learning (ML) in identifying the development of ischaemic stroke in this population., Methods: We performed a post-hoc analysis of the WARCEF trial, only including patients without a history of AF. We evaluated the performance of 9 ML models for identifying incident stroke using metrics including area under the curve (AUC) and decision curve analysis. The importance of each feature used in the model was ranked by SAPley Additive exPlanations (SHAP) values., Results: We included 2213 patients with HFrEF but without AF (mean age 58 ± 11 years; 80% male). Of these, 74 (3.3%) had an ischaemic stroke in sinus rhythm during a mean follow-up of 3.3 ± 1.8 years. Out of the 29 patient-demographics variables, 12 were selected for the ML training. Almost all ML models demonstrated high AUC values, outperforming the CHA 2 DS 2 -VASc score (AUC: 0.643, 95% confidence interval [CI]: 0.512-0.767). The Support Vector Machine (SVM) and XGBoost models achieved the highest AUCs, with 0.874 (95% CI: 0.769-0.959) and 0.873 (95% CI: 0.783-0.953), respectively. The SVM and LightGBM consistently provided significant net clinical benefits. Key features consistently identified across these models were creatinine clearance (CrCl), blood urea nitrogen (BUN) and warfarin use., Conclusions: Machine-learning models can be useful in identifying incident ischaemic strokes in patients with HFrEF but without AF. CrCl, BUN and warfarin use were the key features., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Vitamin D (25(OH)D) deficiency is linked to increased cardiovascular disease (CVD) risk in the general population, but its implications for people with multiple sclerosis (pwMS) remain unexplored. This study aimed to evaluate the association of 25(OH)D with long-term CVD outcomes in pwMS and the impact of vitamin D supplementation., Methods: This observational cohort study analysed anonymised medical records from 70 healthcare organisations following pwMS for 5-years (2019-2024). PwMS and deficient or inadequate 25(OH)D levels were 1:1 propensity-score matched with pwMS and adequate 25(OH)D levels, for demographics, comorbidities, and cardiovascular care. Cox proportional hazard models analysed the incidence of all-cause mortality, stroke, acute myocardial infarction, heart failure, angina, atrial fibrillation/flutter, and a composite measure of major adverse cardiovascular events (MACE). Propensity-matched pwMS who had deficient or inadequate 25(OH)D levels taking cholecalciferol were compared to pwMS and adequate 25(OH)D levels (not taking supplementation)., Results: Amongst 74,372 pwMS, 9 % had deficient 25(OH)D levels, 18 % inadequate, and 73 % adequate. Deficient, or inadequate 25(OH)D levels were associated with an increased rate of MACE (HR, 1.32 [95 % CI: 1.19, 1.46], HR, 1.29 [95 % CI: 1.20, 1.40], respectively) compared to those with adequate levels. Cholecalciferol supplementation in pwMS and deficient or inadequate 25(OH)D levels did not alleviate the higher CVD rate (HR, 1.39 [95 % CI: 1.21,1.60], HR, 1.31 [95 % CI: 1.17, 1.47], respectively) in comparison to those with adequate 25(OH)D levels taking no vitamin D supplementation., Conclusions: Deficient or inadequate 25(OH)D levels in pwMS were associated with an increased rate of MACE, which may not be mitigated by vitamin D supplementation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: The risk of dementia in patients with stroke-heart syndrome (SHS) remains unexplored., Patients and Methods: Retrospective analysis using the TriNetX network, including patients with ischaemic stroke from 2010 to 2020. These patients were categorised into two groups: those with SHS (heart failure, myocardial infarction, ventricular fibrillation, or Takotsubo cardiomyopathy within 30 days post-stroke) and those without SHS. The primary outcome was the 1-year risk of dementia (vascular dementia, dementia in other disease, unspecified dementia, or Alzheimer's disease). The secondary outcome was the 1-year risk of all-cause death. Cox regression analysis after 1:1 propensity score matching (PSM) was performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the outcomes., Results: We included 52,971 patients with SHS (66.6 ± 14.6 years, 42.2% females) and 854,232 patients without SHS (64.7 ± 15.4 years, 48.2% females). Following PSM, 52,970 well-balanced patients were considered in each group. Patients with SHS had a higher risk of incident dementia compared to those without SHS (HR 1.28, 95%CI 1.20-1.36). The risk was the highest during the first 31 days of follow-up (HR 1.51, 95%CI 1.31-1.74) and was mainly driven by vascular and mixed forms. The increased risk of dementia in patients with SHS, was independent of oral anticoagulant use, sex and age but it was the highest in those aged <75 years compared to ⩾75 years., Discussion and Conclusion: SHS is associated with increased risk of dementia. Future studies are needed to develop innovative strategies for preventing complications associated with stroke-heart syndrome and improving the long-term prognosis of these patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: GYHL is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU’s Horizon Europe Research & Innovation programme. BJRB has received research funding from BMS/Pfizer and Huawei Europe. All other authors report no relevant disclosures.

Background: The incidence and outcomes of early cardiac complications in patients with intracerebral hemorrhage (ICH) are poorly understood. These cardiac complications may be part of the so-called stroke-heart syndrome in patients with ICH. We investigated this issue in an individual patient data pooled analysis from an international repository of clinical trial data., Methods: We used the Virtual International Stroke Trials Archive to investigate the incidence of cardiac complications within 30 days post-ICH or acute ischemic stroke (AIS). These complications included acute coronary syndrome encompassing myocardial injury, heart failure/left ventricular dysfunction, atrial fibrillation/atrial flutter, other arrhythmia/ECG abnormalities, and cardiorespiratory arrest. We used propensity score matching to compare the incidence of patients with stroke-heart syndrome in patients with ICH with those following AIS. Factors associated with 90-day mortality were evaluated using multivariate logistic regression analysis in the ICH cohort., Results: We pooled data from 8698 participants recruited in acute stroke trials (mean age, 68±12 years; 56% male), of whom 914 (11%) were patients with ICH. Among the patients with ICH, 123 (13%) had stroke-heart syndrome in patients with ICH. Following propensity score matching, a total of 1828 patients (914 for each of the cohorts) were analyzed. While the overall incidence of cardiac events tended to be lower in the ICH group compared with the AIS group (the cumulative incidence freedom from the event, 86.3% [95% CI, 84.1-88.6] versus 83.6% [95% CI, 81.2-86.0]; P =0.100), the incidences cardiac events other than atrial fibrillation/atrial flutter were comparable between the 2 matched groups. The incidence of atrial fibrillation/atrial flutter was significantly lower in the ICH group than in the AIS group ( P <0.001). The multivariate-adjusted analysis found that stroke-heart syndrome in patients with ICH was associated with 90-day mortality (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]; P <0.001)., Conclusions: Cardiac events are common and negatively affect prognosis in patients with ICH, just as seen in AIS., Competing Interests: Dr Dawson received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Medtronic, and Pfizer and a travel fee from MicroTransponder, Inc. Dr Dawson also received investigator-initiated research funding grant from the Stroke Association United Kingdom. Dr Lip is a consultant and a speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Anthos. No fees are received personally. He is a National Institute for Health and Care Research Senior Investigator and a co-principal investigator of the AFFIRMO project on multimorbidity in AF (grant agreement 899871), the TARGET project on digital twins for personalized management of atrial fibrillation and stroke (grant agreement 101136244), and the ARISTOTELES project on artificial intelligence for management of chronic long-term conditions (grant agreement 101080189), which are all funded by the Horizon Europe Research and Innovation Programme of the European Union. The other authors report no conflicts.

Cranial vault thickness (CVT) and its variations provide valuable insights into an individual's biological attributes such as age and sex. This paper aimed to assess the correlations of CVT with age and sex and develop a regression model for age estimation in Malaysian subadults using computed tomography (CT) images. A total of 521 CT images (male/female: 279/242; age range: 0-20 years; Malay/Chinese/Indian: 221/145/155) were included in the study. Correlations of CVT measurements with age and sex, including frontal bone thickness (FBT), occipital bone thickness (OBT), left parietal bone thickness (LPBT), and right parietal bone thickness (RPBT) were assessed and regression formulae were developed for age estimation in subadults. A significant correlation between CVT measurements and age was demonstrated (p < 0.001). Age estimation was most accurate in the younger age group (< 2 years) at frontal and occipital, and accuracy decreases in the older age groups. Additionally, sexual dimorphism was evident in the frontal and parietal bone thickness within the age range of 3-6 years and 16-20 years, respectively. In conclusion, the findings suggested CVT measurements could be used to corroborate other age estimation methods for subadults., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Adverse cardiac events following ischaemic stroke (stroke-heart syndrome, SHS) pose a clinical challenge. We investigated the association between initial blood pressure at stroke presentation and the risk of SHS., Methods: We utilised data from the Virtual International Stroke Trials Archive (VISTA). We defined SHS as the incidence of cardiac complications within 30 days post-ischaemic stroke. These presentations included acute coronary syndrome encompassing myocardial injury, heart failure/left ventricular dysfunction, atrial fibrillation/flutter, other arrhythmia/electrocardiogram abnormalities, and cardiorespiratory arrest. Using Cox proportional hazards models, we assessed the risk trajectories for developing SHS and its presentations associated with initial blood pressure. We also explored the risk trajectories for 90-day mortality related to initial blood pressure., Results: From 16,095 patients with acute ischaemic stroke, 14,965 (mean age 69 ± 12 years; 55% male) were analysed. Of these, 1774 (11.8%) developed SHS. The risk of SHS and initial blood pressure showed a U-shaped relationship. The lowest blood pressures (⩽130 mmHg systolic and ⩽55 mmHg diastolic) were associated with the highest risks (adjusted hazard ratio [95%confidence interval]: 1.40 [1.21-1.63]; p  < 0.001, 1.71 [1.39-2.10]; p  < 0.001, respectively, compared to referential blood pressure range).Cardiorespiratory arrest posed the greatest risk at higher blood pressure levels (2.34 [1.16-4.73]; p  = 0.017 for systolic blood pressure >190 mmHg), whereas other presentations exhibited the highest risk at lower pressures. The 90-day mortality risk also followed a U-shaped distribution, with greater risks observed at high blood pressure thresholds., Conclusions: There is a U-shaped relationship between initial blood pressure at ischaemic stroke presentation and the risk of subsequent SHS., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HI, BH, WKE, JD and AHAR report no conflicts of interest.GYHL reports Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU’s Horizon Europe Research & Innovation programme.

Background: The patient clinical phenotypes at particularly high risk for early cardiac complications after a recent acute ischaemic stroke (AIS), that is, stroke-heart syndrome (SHS), remain poorly defined. We utilised hierarchical cluster analysis to identify specific phenotypic profiles associated with this risk., Methods: We gathered data on patients with AIS from the Virtual International Stroke Trials Archive, a global repository of clinical trial data. We examined cardiac complications within 30 days post-stroke, including acute coronary syndrome, heart failure, arrhythmias and cardiorespiratory arrest. We employed hierarchical cluster analysis to define distinct phenotypic risk profiles. The incidence/risk of SHS and 90-day mortality were compared across these profiles., Results: We included 12,482 patients (mean age 69 ± 12 years; 55% male), yielding five phenotypes: Profile 1 (' elderly and AF '), Profile 2 (' young and smoker '), Profile 3 (' young '), Profile 4 (' cardiac comorbidities ') and Profile 5 (' hypertension with atherosclerotic comorbidities '). Profiles 4 and 1 exhibited the highest risk for SHS (adjusted HR (95% CI): 2.01 (1.70-2.38) and 1.26 (1.05-1.51), respectively, compared to Profile 3), while Profiles 5 and 2 showed moderate risk and Profile 3 had the lowest risk. Although Profiles 1 and 4 were at the highest risk for most SHS presentations, Profile 5 had the highest risk for cardiorespiratory arrest (adjusted HR (95% CI): 2.99 (1.22-7.34)). The 90-day mortality risk was stratified by phenotype, with the highest risk observed in Profiles 5, and 4., Conclusions: Hierarchical cluster analysis effectively identified phenotypes with the highest risk of SHS and early mortality in patients with AIS., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HI, BH, WKE, JD and AHAR report no conflicts of interest.GYHL reports Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU’s Horizon Europe Research & Innovation programme.

Background: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies., Methods: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients., Results: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31)., Conclusions: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment., (© 2024. The Author(s).)

Background: Assessment of residual thromboembolic risk in patients with atrial fibrillation (AF) prescribed oral anticoagulants (OACs) remains unexplored. We performed hierarchical cluster analysis to identify phenotypic profiles of these patients and their risks of residual thromboembolic events., Methods: We utilised data from non-valvular AF patients on OACs, as documented in phases II and III of the GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) registry. We performed a hierarchical cluster analysis to identify distinct phenotypic profiles. We compared the incidence and risks of thromboembolic events (composite of ischaemic stroke, transient ischaemic attack, or systemic embolism) and related outcomes (major bleeding and all-cause death) across the profiles. We determined the optimal number of profiles through visual inspection of the generated dendrograms., Results: We included 22,410 patients (mean age 70 ± 8 years; 56% male), from which five phenotypes were identified: profile 1 ("uncontrolled hypertension"), profile 2 ("young with a history of coronary artery disease"), profile 3 ("young and obese"), profile 4 ("frailty"), and profile 5 ("non-paroxysmal AF with tachycardia"). Profile 4 was associated with the highest rates of thromboembolic events (1.66/100 person-years [95% confidence interval, 1.46-1.89]), major bleeding (1.92/100 person-years [1.70-2.16]), and death (6.02/100 person-years [5.62-6.43]). Profile 3 was associated with the lowest risk across all measured outcomes (thromboembolic events, 0.64 events/100 person-years [0.48-0.82]; major bleeding, 0.83 events/100 person-years [0.65-1.04]; and death, 1.44 events/100 person-years [1.21-1.71]). Profile 1 had a moderate thromboembolic event rate (1.04/100 person-years [0.91-1.08]), while profiles 2 and 5 showed lower rates., Conclusions: The phenotypic profiles of patients with AF prescribed OACs identified using hierarchical cluster analysis are associated with distinct residual thromboembolic risks and related outcomes. This approach has the potential to enhance patient risk-stratification and holistic approaches to management., (© 2024. The Author(s).)

Introduction: Statins reduce recurrent stroke and cardiovascular events in patients with non-cardioembolic stroke. The benefits of statins in patients with AF and recent IS remain unclear. We aimed to investigate the benefits of statins in patients with AF and recent IS., Patients and Methods: This retrospective, cohort study was conducted using deidentified electronic medical records within TriNetX platform. Patients with AF and recent IS, who received statins within 28 days of their index stroke were propensity score-matched with those who did not. Patients were followed up for up to 2 years. Primary outcomes were the 2-year risk of recurrent IS, all-cause mortality and the composite outcome of all-cause mortality, recurrent IS, transient ischaemic attack (TIA), and acute myocardial infarction (MI). Secondary outcomes were the 2-year risk of TIA, intracranial haemorrhage (ICH), acute MI, and hospital readmission. Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (95%CI)., Results: Of 20,902 patients with AF and recent IS, 7500 (35.9%) received statins within 28 days of their stroke and 13,402 (64.1%) did not. 11,182 patients (mean age 73.7 ± 11.5; 5277 (47.2%) female) remained after propensity score matching. Patients who received early statins had significantly lower risk of recurrent IS (HR: 0.45, 95%CI: 0.41-0.48, p  < 0.001), mortality (HR: 0.75, 95%CI: 0.66-0.84, p  < 0.001), the composite outcome (HR: 0.48, 95%CI: 0.45-0.52, p  < 0.001), TIA (HR: 0.37, 95%CI: 0.30-0.44, p  < 0.001), ICH (HR: 0.59, 95%CI: 0.47-0.72, p  < 0.001 ), acute MI (HR: 0.35, 95%CI: 0.30-0.42, p  < 0.001) and hospital readmission (HR: 0.46, 95%CI: 0.42-0.50, <0.001). Beneficial effects of early statins were evident in the elderly, different ethnic groups, statin dose intensity, and AF subtypes, large vessel occlusion and embolic strokes and within the context of statin lipophilicity, optimal LDL-cholesterol levels, various cardiovascular comorbidities, treatment with intravenous thrombolysis or endovascular thrombectomy, and NIHSS 0-5 and NIHSS > 5 subgroups., Discussion and Conclusion: Patients with AF and recent IS, who received early statins, had a lower risk of recurrent stroke, death, and other cardiovascular outcomes including ICH, compared to those who did not., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SEC, TB, JH, KHY, CTWT, AH and GI report no conflicts of interest.KKL received grants from Croucher Foundation, Research Fund Secretariat of the Food and Health Bureau, Innovation and Technology Bureau, Research Grants Council, Amgen, Boehringer Ingelheim, Eisai and Pfizer; and consultation fees from Amgen, Boehringer Ingelheim, Daiichi Sankyo and Sanofi, all outside the submitted work.GYHL reports Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. GYHL is a National Institute for Health and Care Research Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899871.AHAR reports Member of the Editorial Board of Stroke and European Stroke Journal.

Background and Purpose: The impact of bridging thrombolysis prior to endovascular thrombectomy (EVT) compared to EVT alone on intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH), and death in anticoagulated atrial fibrillation (AF) patients with acute ischaemic stroke (AIS) is not well defined., Methods: A retrospective study was conducted using data from a federated research network (TriNetX) including 114 health care organisations in the United States. Anticoagulated AF patients with AIS who received either bridging thrombolysis (BT) or EVT alone from September 2018 to November 2023 were included. Following propensity score matching, Cox regression analyses examined the risk of ICH, SAH, and death within 30 and 90 days, comparing anticoagulated AF patients receiving BT versus EVT only., Results: A total of 3156 patients with AIS were treated with BT or EVT alone. Following 1:1 propensity score matching, the cohort included 766 patients in each group. ICH occurred within 30 and 90 days in 6.9% and 8.0% in the BT group compared with 7.4% and 7.7% in the EVT-only group (hazard ratios [HR] = 0.92, 95% confidence interval [CI] = 0.63-1.33 and HR = 1.01, 95% CI = 0.71-1.45, respectively). SAH occurred within 30 and 90 days in 4.2% and 4.4% of patients in the BT compared to 3.0% and 3.4% in the EVT-only group (HR = 1.38, 95% CI = 0.81-2.38 and HR = 1.29, 95% CI = 0.77-2.14, respectively). Death occurred within 30 and 90 days in 17.8% and 19.8% of patients in the BT compared to 22.2% and 27.3% in the EVT-only group (HR = 0.77, 95% CI = 0.62-0.97 and HR = 0.65, 95% CI = 0.56-0.86, respectively)., Conclusions: In anticoagulated AF patients with AIS, BT was associated with a significantly lower risk of death, with no difference in ICH or SAH risk within 30 and 90 days compared to EVT only., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: Prolonged cardiac monitoring (PCM) increases atrial fibrillation (AF) detection after ischemic stroke, but access is limited, and it is burdensome for patients. Our objective was to assess whether midregional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) could classify people who are unlikely to have AF after ischemic stroke and allow better targeting of PCM., Methods: We analyzed people from the Biomarker Signature of Stroke Aetiology (BIOSIGNAL) study with ischemic stroke, no known AF, and ≥3 days cardiac monitoring. External validation was performed in the Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient (PRECISE) study of 28 days of cardiac monitoring in people with ischemic stroke or transient ischemic attack and no known AF. The main outcome is no AF detection. We assessed the discriminatory value of MR-proANP and NT-proBNP combined with clinical variables to identify people with no AF. A decision curve analysis was performed with combined data to determine the net reduction in people who would undergo PCM using the models based on a 15% threshold probability for AF detection., Results: We included 621 people from the BIOSIGNAL study. The clinical multivariable prediction model included age, NIH Stroke Scale score, lipid-lowering therapy, creatinine, and smoking status. The area under the receiver-operating characteristic curve (AUROC) for clinical variables was 0.68 (95% CI 0.62-0.74), which improved with the addition of log 10 MR-proANP (0.72, 0.66-0.78; p = 0.001) or log 10 NT-proBNP (0.71, 0.65-0.77; p = 0.009). Performance was similar for the models with log 10 MR-proANP vs log 10 NT-proBNP ( p = 0.28). In 239 people from the PRECISE study, the AUROC for clinical variables was 0.68 (0.59-0.76), which improved with the addition of log 10 NT-proBNP (0.73, 0.65-0.82; p < 0.001) or log 10 MR-proANP (0.79, 0.72-0.86; p < 0.001). Performance was better for the model with log 10 MR-proANP vs log 10 NT-proBNP ( p = 0.03). The models could reduce the number of people who would undergo PCM by 30% (clinical and log 10 MR-proANP), 27% (clinical and log 10 NT-proBNP), or 20% (clinical only)., Discussion: MR-proANP and NT-proBNP help classify people who are unlikely to have AF after ischemic stroke. Measuring MR-proANP or NT-proBNP could reduce the number of people who need PCM by 30%, without reducing the amount of AF detected., Trial Registration Information: NCT02274727; clinicaltrials.gov/study/NCT02274727.

Introduction: Newly diagnosed cardiovascular complications following an ischaemic stroke, termed stroke-heart syndrome, are common and associated with worse outcomes. Little is known regarding stroke-heart syndrome in relation to intracerebral haemorrhage (ICH). This study aimed to investigate the incidence and 5-year major adverse cardiovascular events (MACE; acute myocardial infarction, ischaemic stroke, all-cause mortality and recurrent ICH) of newly diagnosed cardiovascular complications following incident ICH, using a global federated database., Patients and Methods: A retrospective cohort study was conducted using anonymised electronic medical records. Patients aged ⩾ 18 years with non-traumatic ICH and 5-year follow-up were included. Patients with newly diagnosed cardiovascular complications within 4-weeks following the initial ICH were 1:1 propensity score-matched with patients without new-onset cardiovascular complications. Each cardiovascular complications were investigated as a composite stroke-heart syndrome cohort and separately for associated MACE. Cox hazard regression models were used to determine 5-year incidence of MACE., Results: Before propensity score matching, 171,489 patients with non-traumatic ICH, 15% ( n  = 26,449) experienced ⩾1 newly diagnosed cardiovascular complication within 4 weeks. After matching, patients with ICH and cardiovascular complications were associated with a significantly higher risk of 5-year MACE (HR 1.35 [95% CI 1.32-1.38]), and in each composite compared to matched controls. There was no significant risk of rehospitalisation over 5-year follow-up [HR 0.90 [0.73-1.13]). The risk of MACE was significantly higher in patients with newly diagnosed cardiovascular complications., Discussion and Conclusions: Newly diagnosed cardiovascular complications following ICH (i.e. stroke-heart syndrome) were common and associated with a significantly worsened 5-year prognosis., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BB has received research funding from BMS/Pfizer. GYHL is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No. 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No. 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No. 101080189), which are all funded by the EU’s Horizon Europe Research & Innovation programme.

Background: Few studies have investigated the role of social determinants of health (SDoH) in patients with atrial fibrillation (AF)., Aim: To investigate the relationship between SDoH and adverse events in a large multinational AF cohort., Design: Retrospective study utilizing a global federated health research network (TriNetX)., Methods: Patients with AF were categorized as socially deprived defined according to ICD codes based on three SDoHs: (i) extreme poverty; (ii) unemployment; and/or (iii) problems related with living alone. The outcomes were the 5-year risk of a composite outcomes of all-cause death, hospitalization, ischemic heart disease (IHD), stroke, heart failure (HF) or severe ventricular arrhythmias. Cox regression was used to compute hazard rate ratios (HRs) and 95% confidence intervals (CIs) following 1:1 propensity score matching (PSM)., Results: The study included 24 631 socially deprived (68.8 ± 16.0 years; females 51.8%) and 2 462 092 non-deprived AF patients (75.5 ± 13.1 years; females 43.8%). Before PSM, socially deprived patients had a higher risk of the composite outcome (HR 1.9, 95% CI 1.87-1.93), all-cause death (HR 1.34, 95% CI 1.28-1.39), hospitalization (HR 2.01, 95% CI 1.98-2.04), IHD (HR 1.67, 95% CI 1.64-1.70), stroke (HR 2.60, 95% CI 2.51-2.64), HF (HR 1.91, 95% CI 1.86-1.96) and severe ventricular arrhythmias (HR 1.83, 95% CI 1.76-1.90) compared to non-deprived AF patients. The PSM-based hazard ratios for the primary composite outcome were 1.54 (95% CI 1.49-1.60) for the unemployed AF patients; 1.39 (95% CI 1.31-1.47) for patients with extreme poverty or with low income; and 1.42 (95% CI 1.37-1.47) for those with problems related with living alone., Conclusions: In patients with AF, social deprivation is associated with an increased risk of death and adverse cardiac events. The presence of possible unmeasured bias associated with the retrospective design requires confirmation in future prospective studies., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Association of Physicians.)

Neurostimulation, the use of electrical stimulation to modulate the activity of the nervous system, is now commonly used for the treatment of chronic pain, movement disorders and epilepsy. Many neurostimulation techniques have now shown promise for the treatment of physical impairments in people with stroke. In 2021, vagus nerve stimulation was approved by the FDA as an adjunct to intensive rehabilitation therapy for the treatment of chronic upper extremity deficits after ischaemic stroke. In 2024, pharyngeal electrical stimulation was conditionally approved by the UK National Institute for Health and Care Excellence for neurogenic dysphagia in people with stroke who have a tracheostomy. Many other approaches have also been tested in pivotal device trials and a number of approaches are in early-phase study. Typically, neurostimulation techniques aim to increase neuroplasticity in response to training and rehabilitation, although the putative mechanisms of action differ and are not fully understood. Neurostimulation techniques offer a number of practical advantages for use after stroke, such as precise dosing and timing, but can be invasive and costly to implement. This Review focuses on neurostimulation techniques that are now in clinical use or that have reached the stage of pivotal trials and show considerable promise for the treatment of post-stroke impairments., (© 2024. Springer Nature Limited.)

The management of ischaemic stroke survivors is multidisciplinary, necessitating the collaboration of numerous medical professionals and rehabilitation specialists. However, due to the lack of comprehensive and holistic follow-up, their post-discharge management may be suboptimal. Achieving this holistic, patient-centred follow-up requires coordination and interaction of subspecialties, which general practitioners can provide as the first point of contact in healthcare systems. This approach can improve the management of stroke survivors by preventing recurrent stroke through an integrated post-stroke care, including appropriate Antithrombotic therapy, assisting them to have a Better functional and physiological status, early recognition and intervention of Comorbidities, and lifestyles. For such work to succeed, close interdisciplinary collaboration between primary care physicians and other medical specialists is required in a holistic or integrated way., (© 2023. The Author(s).)

Background: No studies have investigated the association between albumin levels and the risk of early cardiovascular complications in patients with ischemic stroke., Methods: Retrospective analysis with a federated research network (TriNetX) based on electronic medical records ( International Classification of Diseases-Tenth Revision-Clinical Modification and logical observation identifiers names and codes) mainly reported between 2000 and 2023, from 80 health care organizations in the United States. Based on albumin levels measured at admission to the hospital, patients with ischemic stroke were categorized into 2 groups: (1) reduced (≤3.4 g/dL) and (2) normal (≥3.5 g/dL) albumin levels. The primary outcome was a composite of all-cause death, heart failure, atrial fibrillation, ventricular arrhythmias, myocardial infarction, and Takotsubo cardiomyopathy 30 days from the stroke. Secondary outcomes were the risk for each component of the primary outcome. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching., Results: Overall, 320 111 patients with stroke had normal albumin levels (70.9±14.7 years; 48.9% females) and 183 729 (57.4%) had reduced albumin levels (72.9±14.3 years; 50.3% females). After propensity score matching, the primary outcomes occurred in 36.0% of patients with reduced and 26.1% with normal albumin levels (HR, 1.48 [95% CI, 1.46-1.50]). The higher risk in patients with reduced albumin levels was consistent also for all-cause death (HR, 2.77 [95% CI, 2.70-2.84]), heart failure (HR, 1.31 [95% CI, 1.29-1.34]), atrial fibrillation (HR, 1.11 [95% CI, 1.09-1.13]), ventricular arrhythmias (HR, 1.38 [95% CI, 1.30-1.46]), myocardial infarction (HR, 1.60 [95% CI, 1.54-1.65]), and Takotsubo cardiomyopathy (HR, 1.51 [95% CI, 1.26-1.82]). The association between albumin levels and the risk of cardiovascular events was independent of advanced age, sex, multimorbidity, and other causes of hypoalbuminemia. A progressively increased risk of adverse events was found in patients with mild and severe reduced compared to normal albumin levels., Conclusions: Albumin levels are associated with the risk of early cardiovascular events and death in patients with ischemic stroke. The potential pathophysiological or therapeutic roles of albumin in patients with stroke warrant further investigation., Competing Interests: Disclosures Dr Lip is a consultant and speaker for Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Anthos and Daiichi-Sankyo. No fees are received personally. Dr Lip is co-principal investigator of the AFFIRMO project (Atrial Fibrillation Integrated Approach in Frail, Multimorbid and Polymedicated Older People) on multimorbidity in atrial fibrillation, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 899871. The other authors report no conflicts.

Introduction Existing randomised controlled trials assessing the safety and efficacy of left atrial appendage occlusion (LAAO) in atrial fibrillation (AF) were of relatively small sample size, or included patients who could receive oral anticoagulant treatment after device implantation. We compared the outcomes of patients with newly diagnosed AF who received percutaneous LAAO or direct oral anticoagulants (DOAC) treatment, in a large population from a global federated health network (TriNetX). Methods Patients with AF treated with percutaneous LAAO were matched with those treated with DOAC between 1st December 2010 and 1st October 2018. Outcomes were all-cause mortality, ischaemic stroke and intracranial haemorrhage (ICH) at 5 years. Results We included 200 patients with AF, who received either LAAO or DOAC. The risk of all-cause mortality, ischaemic stroke and ICH at 5 years was not significantly different between the two groups (Risk Ratio [RR] for all-cause mortality: 1.52, 95% confidence interval (CI): 0.97- 2.38, RR for ischaemic stroke: 1.09, 95% CI: 0.51- 2.36, and RR for ICH: 1.0, 95% CI: 0.44- 2.30). Conclusion Patients newly diagnosed with AF, eligible for DOAC, showed similar 5-year risk of death, ischemic stroke, and ICH when comparing those who underwent percutaneous LAAO to those receiving DOAC. Future randomised controlled trials are needed to confirm the findings and advise changes in guidelines., (S. Karger AG, Basel.)

Atrial fibrillation (AF) is common and warrants consideration of oral anticoagulant (OAC) medication. Usually, the decision is straightforward, following the pathway outlined in the European Society of Cardiology's guideline; however, certain situations fall outside of this evidence base - such as a diagnosis of subclinical AF made via implanted devices or wearable electrocardiogram monitors, or alternatively diagnosis of 'secondary AF' following a major stressor. Subclinical AF is associated with stroke, though not to the extent of clinical AF, and the benefits of anticoagulation appear to be lower. Longer episodes are more clinically meaningful, and recent randomised controlled trials have demonstrated that some patients derive benefit from OAC. Similarly, when AF is triggered by sepsis or non-cardiac surgery, specific evidence supporting OAC initiation is lacking and clinician behaviour is variable. Observational data demonstrate poorer outcomes in these patients, implying that the perception of a transient, reversible phenomenon may not be correct. Contrastingly, cardiac surgery very frequently induces AF, and the benefits of anticoagulation rarely outweigh the risks of bleeding. Following ischaemic stroke, recent evidence suggests that early (re-)initiation of OAC should be considered as this does not increase the risk of haemorrhagic transformation as previously hypothesised. This narrative review summarises the available literature and outlines, where possible, practical advice for clinicians facing these common clinical dilemmas.

Atrial fibrillation (AF) and stroke remain a major cause of morbidity and mortality. The two conditions shared common co-morbidities and risk factors. AF-related strokes are associated with worse clinical outcomes and higher mortality compared to non-AF-related. Early detection of AF is vital for prevention. While various scores have been developed to predict AF in such a high-risk group, they are yet to incorporated into clinical guidelines. Novel markers and predictors of AF including coronary and intracranial arterial calcification have also been studied. There are also ongoing debates on the management of acute stroke in patients with AF, and those who experienced breakthrough stroke while on oral anticoagulants. We provided an overview of the complex interplay between AF and stroke, as well as the treatment and secondary prevention of stroke in AF. We also comprehensively discussed the current evidence and the ongoing conundrums, and highlighted the future directions on the topic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

The risks of cardiovascular events (CVEs) in people with epilepsy (PWE) are not well understood. To establish the short- and long-term burden of CVEs in PWE. Electronic health records from a global federated health research network (TriNetX) were used to establish a cohort of PWE. Primary outcomes were: (1) the proportion of people experiencing a composite outcome of cardiac arrest, acute heart failure (HF), acute coronary syndrome (ACS), atrial fibrillation (AF), severe ventricular arrhythmia or all-cause death within 30 days of a seizure; and (2) the 5-year risk for a composite outcome of ischemic heart diseases, stroke, hospitalization, or all-cause death in the PWE experiencing early CVEs. Cox-regression analyses with propensity score matching was used to produce hazard ratios (HRs) and 95% confidence intervals (CI). In 271,172 PWE (mean age 50 ± 20 years; 52% females), the 30-day risk of CVEs following seizure was: 8.7% for the composite outcome, 0.9% for cardiac arrest, 0.8% for HF, 1.2% for ACS, 4.1% for AF, 0.7% for severe ventricular arrhythmias, and 1.6% for all-cause death. For the 15,120 PWE experiencing CVEs within 30 days of seizure, the 5-year adjusted risks for all composite outcomes measured were significantly increased (overall HR: 2.44, 95% CI 2.37-2.51), ischemic heart diseases HR 3.23 (95% CI 3.10-3.36), stroke HR 1.56 (95% CI 1.48-1.64), hospitalization HR 2.03 (95% CI 1.97-2.10), and all-cause death HR 2.75 (95% CI 2.61-2.89). The large proportions of PWE with active disease that experience CVEs and the poor long-term outcome associated suggest the existence of an "epilepsy-heart syndrome.", Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gregory Y.H. Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. All other authors report no disclosures., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: None declared.

Purpose of Review: Atrial fibrillation (AF) is a major risk factor for systemic embolism and ischaemic stroke. Furthermore, AF-related strokes are associated with higher mortality, greater disability, longer hospital stays and lower rates of hospital discharge than strokes caused by other reasons. The aim of this review to summarise the existing evidence on the association of AF with ischemic stroke and provide insights on the pathophysiological mechanisms and the clinical management of patients with AF in order to reduce the burden of ischemic stroke., Recent Findings: Beyond Virchow's triad, several pathophysiological mechanisms associated with structural changes in the left atrium, which may precede the identification of AF, may contribute to the increased risk of arterial embolism in AF patients. Individualised thromboembolic risk stratification based on CHA 2 DS 2 -VASc score and clinically relevant biomarkers provides essential tool towards a personalised holistic approach in thromboembolism prevention. Anticoagulation remains the cornerstone of stroke prevention moving from vitamin K antagonists (VKA) to safer non-vitamin K direct oral anticoagulants in the majority of AF patients. Despite the efficacy and safety of oral anticoagulation, still the equilibrium between thrombosis and haemostasis in AF patients remains suboptimal and future directions in anticoagulation and cardiac intervention may provide novel treatment options in stroke prevention. This review summarises the pathophysiologic mechanisms of thromboembolism, aiming the current and potential future perspectives in stroke prevention in AF patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Reliability, or repeatability, of permanent tooth staging techniques is usually expressed as Cohen's Kappa. This single value obscures information about the quantity and allocation of disagreements. In this study we assess and compare intra-observer reliability of permanent tooth staging techniques described by Nolla, Moorrees et al. and Demirjian et al. The sample was panoramic radiographs of healthy dental patients made up of 100 males and 100 females aged 6-15 years. All permanent teeth on the left side (excluding third molars) were scored twice. Weighted Kappa and percentage agreement were calculated. Results show Kappa values for all teeth combined as 0.918, 0.922 and 0.938 for Demirjian (number of teeth N = 2682), Nolla (N = 2698) and Moorrees (N = 2674) respectively. A comparison of Kappa values between upper and lower teeth showed marginally higher values for upper incisors and lower molar for all three scoring methods. Small differences in Kappa values were noted between tooth types with the upper first molar having smaller values than other teeth. Percentage agreement ranged from 81 % (Moorrees), 86 % (Nolla) to 87 % (Demirjian). Tooth stage differences between first and second assessments were not more than one stage. Our findings show that Demirjian scoring is marginally more reliable than Nolla or Moorrees. We suggest that (1) data for reliability are tabulated in full to show the quantity and allocation of disagreement between first and second readings, and (2) that the reliability sample is sufficiently large with a wide age range to include multiple different tooth stages., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Stroke is one of the leading causes of mortality and morbidity globally. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is set to reach epidemic proportions. AF is associated with a five-fold increase in risk of stroke. Strokes caused by AF more often are fatal or result in severe disability. Even though the incidence of stroke has been significantly reduced by oral anticoagulation, AF is thought to account for a significant proportion of cryptogenic strokes where no etiology is identified., Areas Covered: This article reviews the literature related to AF and stroke, pathophysiological insights, diagnosis of AF in stroke patients, and its management (Graphical Abstract)., Expert Opinion: The pathophysiology of thrombogenesis that links AF and stroke is not well understood and is an area of active research to identify new therapeutic targets to prevent AF and stroke. As the nature of AF and stroke is multifaceted, an integrated care approach to managing AF and stroke is increasingly essential.

Cardiac rhythm monitoring is performed to search for atrial fibrillation (AF) after ischaemic stroke or transient ischaemic attack (TIA). Prolonged cardiac rhythm monitoring increases AF detection but is challenging to implement in many healthcare settings and is not needed for all people after ischaemic stroke/TIA. We aimed to develop and validate a model that includes clinical, electrocardiogram (ECG), blood-based, and genetic biomarkers to identify people with a low probability of AF detection after ischaemic stroke or TIA. We will recruit 675 consenting participants who are aged over 18 years, who were admitted with ischaemic stroke or TIA in the 5 days prior, who are not known to have AF, and who would be suitable for anticoagulation if AF is found. We will collect baseline demographic and clinical data, a 12-lead ECG, and a venous blood sample for blood biomarkers (including midregional pro-atrial natriuretic peptide, MRproANP) and genetic data. We will perform up to 28 days of cardiac rhythm monitoring using an R-test or patch device to search for AF in all participants. The sample size of 675 participants is based on true sensitivity of 92.5%, null hypothesis sensitivity of 80%, 80% power, and 5% significance. The primary outcome is AF detection ≥30 s duration during 28 days of cardiac rhythm monitoring. Secondary outcomes are AF detection at 1-year, recurrent cardiovascular events, and mortality and will be identified by electronic linkage and telephone follow-up. The results will guide the development of a more personalized care pathway to search for AF after ischaemic stroke or TIA. This could help to reduce cardiac rhythm monitoring for people with a low probability of AF detection and allow more intensive cardiac monitoring to be focused on people who are more likely to have AF and benefit. Participants will be consented for their data to be used in future research studies, providing a rich resource for stroke and cardiovascular research communities., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

The use of a paired vagus nerve stimulation (VNS) system for the treatment of moderate-to-severe upper extremity motor deficits associated with chronic ischemic stroke has recently been approved by the US Food and Drug Administration. This treatment aims to increase the task-specific neuroplasticity through the activation of cholinergic and noradrenergic networks during rehabilitation therapy. A recent pivotal Phase III trial showed that VNS paired with rehabilitation led to improvements in upper extremity impairment and function in people with moderate-to-severe arm weakness for an average of 3 years after ischemic stroke. The between-group difference following 6 weeks of in-clinic therapy and 90 days of home exercise therapy was three points on the upper extremity Fugl-Meyer score. A clinically meaningful response defined as a greater than or equal to six-point improvement was seen in approximately half of the people treated with VNS compared to approximately a quarter of people treated with rehabilitation alone. Further post-marketing research should aim to establish whether the treatment is also of use for people with intracerebral hemorrhage, in people with more severe arm weakness, and for other post-stroke impairments. In addition, high-quality randomized studies of non-invasive VNS are required.

Aims: Patients with heart failure with reduced ejection fraction (HFrEF) are at significant risk of stroke. Anticoagulation reduces this risk in patients with and without atrial fibrillation (AF), but the risk-to-benefit balance in the latter group, overall, is not favourable. Identification of patients with HFrEF, without AF, at the highest risk of stroke may allow targeted and safer use of prophylactic anticoagulant therapy., Methods and Results: In a pooled patient-level cohort of the PARADIGM-HF, ATMOSPHERE, and DAPA-HF trials, a previously derived simple risk model for stroke, consisting of three variables (history of prior stroke, insulin-treated diabetes, and plasma N-terminal pro-B-type natriuretic peptide level), was validated. Of the 20 159 patients included, 12 751 patients did not have AF at baseline. Among patients without AF, 346 (2.7%) experienced a stroke over a median follow up of 2.0 years (rate 11.7 per 1000 patient-years). The risk for stroke increased with increasing risk score: fourth quintile hazard ratio (HR) 2.35 [95% confidence interval (CI) 1.60-3.45]; fifth quintile HR 3.73 (95% CI 2.58-5.38), with the first quintile as reference. For patients in the top quintile, the rate of stroke was 21.2 per 1000 patient-years, similar to participants with AF not receiving anticoagulation (20.1 per 1000 patient-years). Model discrimination was good with a C-index of 0.84 (0.75-0.91)., Conclusion: It is possible to identify a subset of HFrEF patients without AF with a stroke-risk equivalent to that of patients with AF who are not anticoagulated. In these patients, the risk-to-benefit balance might justify the use of prophylactic anticoagulation, but this hypothesis needs to be tested prospectively., Competing Interests: Conflict of interest: T.K. received speaker fees from Abbott, Ono Pharma, Otsuka Pharma, Novartis, AstraZeneca, Bristol-Myers Squibb, and Abiomed. A.T. have no disclosures to report. W.T.A. has received personal fees from Abbott; has received consulting fees from Boehringer Ingelheim, CVRx, Edwards Lifesciences, Impulse Dynamics, and Respicardia; has received salary support from V-Wave Medical; and has received research support from the NHLBI, all for studies performed within the heart failure arena. A.S.D. has received grants and personal fees from AstraZeneca during the conduct of the study; personal fees from Abbott, Biofourmis, Boston Scientific, Boehringer Ingelheim, Corvidia, DalCor Pharma, Relypsa, Regeneron, and Merck; grants and personal fees from Alnylam and Novartis; and personal fees from Amgen, outside the submitted work. K.D. has received honoraria and/or research support from Medtronic, Boston Scientific, St Jude, Biotronik, Sorin, Merck, Novartis, Amgen, Boehringer Ingelheim, AstraZeneca, Pfizer, Bayer, GlaxoSmithKline, Roche, Sanofi, Abbott, Otsuka, Leo, Servier, and Bristol-Meyers Squibb. S.E.I. has served on clinical trial committees or as a consultant to AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Lexicon, Merck, Pfizer, vTv Therapeutics, Abbott, and Esperion; and has given lectures sponsored by AstraZeneca, and Boehringer Ingelheim. L.K. has received financial from AstraZeneca; and personal fees from Novartis and Bristol Myers Squibb as a speaker. M.N.K. has received research grant support from AstraZeneca, and Boehringer Ingelheim; has served as a consultant or on an advisory board for Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, and Vifor Pharma; has received other research support from AstraZeneca; and has received honorarium from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. F.A.M. has received personal fees from AstraZeneca. Mi.P. reports consulting fees from AbbVie, Akcea, Actavis, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiorentis, Daiichi Sankyo, Gilead, Johnson & Johnson, Novo Nordisk, Pfizer, Relypsa, Sanofi, Synthetic Biologics, and Theravance. Ma.P. is supported by the British Heart Foundation Centre of Research Excellence Award (RE/13/5/30177 and RE/18/6/34217þ); has received research funding from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Medtronic, Novartis, Novo Nordisk, Pharmacosmos, Roche, and SQ Innovations; and has served as a consultant and on Clinical Trials Committees for Abbvie, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiorentis, Medtronic, Novartis, Novo Nordisk, Pharmacosmos, Siemens, and Takeda. P.P. has received personal fees from Boehringer Ingelheim, AstraZeneca, Servier, Bristol Myers Squib, Amgen, Novartis, Merck, Pfizer, and Berlin Chemie; and has received grants and personal fees from Vifor Pharma. J.L.R. reports grants and consulting fees from Novartis and consulting fees from Abbott, AstraZeneca, MyoKardia, and Sanofi. K.S. reports honoraria from AstraZeneca, Boehringer Ingelheim, and Novartis. M.S.S. has received grants and personal fees from AstraZeneca during the conduct of the study; and has received grants and personal fees from Amgen, Intarcia, Janssen Research and Development, Medicines Company, MedImmune, Merck, and Novartis; and has received personal fees from Anthos Therapeutics, Bristol-Myers Squibb, CVS Caremark, DalCor, Dyrnamix, Esperion, IFM Therapeutics, Ionis; and has received grants from Daiichi Sankyo, Bayer, Pfizer, Poxel, Eisai, GlaxoSmithKline, Quark Pharmaceuticals, and Takeda outside the submitted work; and is a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women’s Hospital from Abbott, Aralez, Roche, and Zora Biosciences. K.S. reports honoraria from AstraZeneca, Boehringer Ingelheim and Novartis. M.R.Z. reports research funding from Novartis and has been a consultant for Novartis, Abbott, Boston Scientific, CVRx, EBR, Endotronics, Ironwood, Merck, Medtronic, and Myokardia V-Wave. S.D.S. has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellPro-Thera, Moderna, American Regent, and Sarepta. P.S.J.’s employer has been remunerated for his work on clinical trials from AstraZeneca, Bayer, Novo Nordisk, and Novartis. Consulting and speakers fees Novartis, AstraZeneca, Boheringer Ingelheim, research funding Boehringer Ingelheim. J.J.V.M. has received payments through Glasgow University from work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, DalCor, GSK, Ionis, KBP Biosciences, Novartis, Pfizer, Theracos Personal lecture fees: the Corpus, Abbott, Hikma, Sun Pharmaceuticals, Medscape/Heart.Org, Radcliffe Cardiology, Servier Director, Global Clinical Trial Partners (GCTP)., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Background: The use of cardiac monitoring to detect atrial fibrillation (AF) is routine after ischaemic stroke but is often delayed leaving patients at risk from undetected AF. We sought to improve the detection of AF by delivering early prolonged 'in-house' cardiac monitoring., Methods: We collected 3-months of data of people with stroke/transient ischaemic attack (TIA), but without AF, who underwent cardiac monitoring (Phase 1, pre-quality improvement project (QIP)). We then implemented an 'in-house' 7-day cardiac monitoring service for 12 months (Phase 2, during QIP)., Results: We included 244 people in Phase 1 and 172 in Phase 2. In Phase 1, 232 (95%) people completed cardiac monitoring. Of these, new AF was detected in 10 (4%). Median time from stroke/TIA onset to availability of the monitoring report in Phase 1 was 50 (interquartile range (IQR): 24-123) days. In Phase 2, 166 (97%) of people completed 7-day cardiac monitoring, with new AF detected in 17 (10%). Median time from onset to availability of the report in Phase 2 was 12 (IQR: 9-15) days. In people with AF detected, 'in-house' monitoring reduced the time of stroke/TIA onset to anticoagulant commencement from 41 (Phase 1) to 14 (Phase 2) days., Discussion: The QIP has improved AF detection, reduced delays associated with conventional cardiac monitoring and prompted early initiation of oral anticoagulation.

In this work, we presented experimental observation on solution-processed bulk heterojunction organic photodiode using vanadyl 2,11,20,29-tetra tert-butyl 2,3 naphthalocyanine (VTTBNc) as a p-type material. VTTBNc is blended with two different acceptors, which are PC 61 BM and PC 71 BM, to offer further understanding in evaluating the performance in organic photodiode (OPD). The blend film of VTTBNc:PC 71 BM with a volumetric ratio of 1:1 exhibits optimized performance in the VTTBNc blend structure with 2.31 × 10 9 Jones detectivity and 26.11 mA/W responsivity at a -1 V bias. The response and recovery time of VTTBNc:PC 71 BM were recorded as 241 ms and 310 ms, respectively. The light absorption measurement demonstrated that VTTBNc could extend the light absorption to the near-infrared (NIR) region. The detail of the enhancement of the performance by adding VTTBNc to the blend was further explained in the discussion section.

[Figure: see text].

Background: Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. There are currently no pharmacological treatments recommended for improving either cognition or function in people with VCI. Three cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) are licenced for the treatment of dementia due to Alzheimer's disease. They are thought to work by compensating for reduced cholinergic neurotransmission, which is also a feature of VCI. Through pairwise comparisons with placebo and a network meta-analysis, we sought to determine whether these medications are effective in VCI and whether there are differences between them with regard to efficacy or adverse events., Objectives: (1) To assess the efficacy and safety of cholinesterase inhibitors in the treatment of adults with vascular dementia and other VCI. (2) To compare the effects of different cholinesterase inhibitors on cognition and adverse events, using network meta-analysis., Search Methods: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 19 August 2020., Selection Criteria: We included randomised controlled trials in which donepezil, galantamine, or rivastigmine was compared with placebo or in which the drugs were compared with each other in adults with vascular dementia or other VCI (excluding cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)). We included all drug doses and routes of administration., Data Collection and Analysis: Two review authors independently identified eligible trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the certainty of the evidence. The primary outcomes were cognition, clinical global impression, function (performance of activities of daily living), and adverse events. Secondary outcomes were serious adverse events, incidence of development of new dementia, behavioural disturbance, carer burden, institutionalisation, quality of life and death. For the pairwise analyses, we pooled outcome data at similar time points using random-effects methods. We also performed a network meta-analysis using Bayesian methods., Main Results: We included eight trials (4373 participants) in the review. Three trials studied donepezil 5 mg or 10 mg daily (n= 2193); three trials studied rivastigmine at a maximum daily dose of 3 to 12 mg (n= 800); and two trials studied galantamine at a maximum daily dose of 16 to 24 mg (n= 1380). The trials included participants with possible or probable vascular dementia or cognitive impairment following stroke. Mean ages were between 72.2 and 73.9 years. All of the trials were at low or unclear risk of bias in all domains, and the evidence ranged from very low to high level of certainty. For cognition, the results showed that donepezil 5 mg improves cognition slightly, although the size of the effect is unlikely to be clinically important (mean difference (MD) -0.92 Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) points (range 0 to 70), 95% confidence interval (CI) -1.44 to -0.40; high-certainty evidence). Donepezil 10 mg (MD -2.21 ADAS-Cog points, 95% CI -3.07 to -1.35; moderate-certainty evidence) and galantamine 16 to 24 mg (MD -2.01 ADAS-Cog point, 95%CI -3.18 to -0.85; moderate-certainty evidence) probably also improve cognition, although the larger effect estimates still may not be clinically important. With low certainty, there may be little to no effect of rivastigmine 3 to 12 mg daily on cognition (MD 0.03 ADAS-Cog points, 95% CI -3.04 to 3.10; low-certainty evidence). Adverse events reported in the studies included nausea and/or vomiting, diarrhoea, dizziness, headache, and hypertension. The results showed that there was probably little to no difference between donepezil 5 mg and placebo in the number of adverse events (odds ratio (OR) 1.22, 95% CI 0.94 to 1.58; moderate-certainty evidence), but there were slightly more adverse events with donepezil 10 mg than with placebo (OR 1.95, 95% CI 1.20 to 3.15; high-certainty evidence). The effect of rivastigmine 3 to 12 mg on adverse events was very uncertain (OR 3.21, 95% CI 0.36 to 28.88; very low-certainty evidence). Galantamine 16 to 24 mg is probably associated with a slight excess of adverse events over placebo (OR 1.57, 95% CI 1.02 to 2.43; moderate-certainty evidence). In the network meta-analysis (NMA), we included cognition to represent benefit, and adverse events to represent harm. All drugs ranked above placebo for cognition and below placebo for adverse events. We found donepezil 10 mg to rank first in terms of benefit, but third in terms of harms, when considering the network estimates and quality of evidence. Galantamine was ranked second in terms of both benefit and harm. Rivastigmine had the lowest ranking of the cholinesterase inhibitors in both benefit and harm NMA estimates, but this may reflect possibly inadequate doses received by some trial participants and small trial sample sizes., Authors' Conclusions: We found moderate- to high-certainty evidence that donepezil 5 mg, donepezil 10 mg, and galantamine have a slight beneficial effect on cognition in people with VCI, although the size of the change is unlikely to be clinically important. Donepezil 10 mg and galantamine 16 to 24 mg are probably associated with more adverse events than placebo. The evidence for rivastigmine was less certain. The data suggest that donepezil 10 mg has the greatest effect on cognition, but at the cost of adverse effects. The effect is modest, but in the absence of any other treatments, people living with VCI may still wish to consider the use of these agents. Further research into rivastigmine is needed, including the use of transdermal patches., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, we performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials. The main Mendelian randomization analyses showed that every 1-SD increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio, 1.19 [95% CI, 1.10-1.30]; P =4×10 -5 ), peripheral artery disease (1.12 [95% CI, 1.03-1.21]; P =9×10 -3 ), and stroke (1.11 [95% CI, 1.05-1.18]; P =2×10 -4 ). In Mendelian randomization mediation analyses, elevated blood pressure was estimated to mediate approximately one-third of the effect of urate on cardiovascular disease risk. Systematic review and meta-analysis of randomized controlled trials showed a favorable effect of urate-lowering treatment on systolic blood pressure (mean difference, -2.55 mm Hg [95% CI, -4.06 to -1.05]; P =1×10 -3 ) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22-0.73]; P =3×10 -3 ) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44-1.03]; P =0.07). In summary, these Mendelian randomization and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on cardiovascular disease risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate lowering may be of cardiovascular benefit.

Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing., Materials and Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke., Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80)., Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events., Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT., (© European Stroke Organisation 2020.)

Background and Purpose: Early neurological deterioration (END) after stroke onset may predict severe outcomes. Estimated rates of END after intravenous thrombolysis among small patient samples have been reported up to 29.8%. We studied the incidence and factors associated with END among patients following intravenous thrombolysis., Methods: We analyzed SITS-International Stroke Thrombolysis registry patients with known outcomes enrolled in 2010 to 2017. END was defined as an increase in National Institutes of Health Stroke Scale score ≥4 or death within 24 hours from baseline National Institutes of Health Stroke Scale. We determined the incidence of END and used logistic regression models to inspect its associated factors. We adjusted for variables found significant in univariate analyses ( P <0.05). Main outcomes were incidence of END, associated predictors of END, ordinal day-90 mRS, and day-90 mortality., Results: We excluded 53 539 patients and included 50 726 patients. The incidence of END was 3415/50 726 (6.7% [95% CI, 6.5%-7.0%]). Factors independently associated with END on multivariate analysis were intracerebral hemorrhage (OR, 3.23 [95% CI, 2.96-3.54], P <0.001), large vessel disease (LVD) with carotid stenosis (OR, 2.97 [95% CI, 2.45-3.61], P <0.001), other LVD (OR, 2.41 [95% CI, 2.03-2.88], P <0.001), and ischemic stroke versus transient ischemic attack (TIA)/stroke mimics (OR, 16.14 [95% CI, 3.99-65.3], P <0.001). END was associated with worse outcome on ordinal mRS: adjusted OR 2.48 (95% CI, 2.39-2.57, P <0.001) by day-90 compared with no END. The adjusted OR for day-90 mortality was 9.70 (95% CI, 8.36-11.26, P <0.001)., Conclusions: The routinely observed rate of END reflected by real-world data is low, but END greatly increases risk of disability and mortality. Readily identifiable factors predict END and may help with understanding causal mechanisms to assist prevention of END.

Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention., Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features., Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02])., Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant.

Introduction: There is conflicting evidence on the impact of atrial fibrillation (AF) type, i.e. non-paroxysmal AF or paroxysmal AF, on thromboembolic recurrence. The consensus of risk equivalence is greatly based on historical evidence, focussing on initial stroke risks. We conducted a systematic review and meta-analysis to describe the impact of AF type on the risk of thromboembolic recurrence, mortality and major haemorrhage in patients with previous stroke., Methods: We systematically searched four multidisciplinary databases from inception to December 2018. We selected observational studies investigating clinical outcomes in patients with ischaemic stroke and AF, stratified by AF type. We assessed all included studies for risk of bias using the 'Risk of Bias In Non-randomised Studies - of Exposures' tool. The Comprehensive Meta-Analysis Software was used to calculate odds ratios from crude event rates., Results: After reviewing 14,127 citations, we selected 108 studies for full-text screening. We extracted data from a total of 26 studies, reporting outcomes on 23,054 patients. Overall, risk of bias was moderate. The annual incidence rates of thromboembolism in patients with non-paroxysmal AF and paroxysmal AF were 7.1% (95% confidence interval: 4.2-11.7) and 5.2% (95% confidence interval: 3.2-8.2), respectively. The odds ratio for thromboembolism in patients with non-paroxysmal AF versus paroxysmal AF was 1.47 (95% confidence interval: 1.08-1.99, p  = 0.013). The annual mortality rates in patients with non-paroxysmal AF and paroxysmal AF were 20.0% (95% confidence interval: 13.2-28.0) and 10.1% (95% confidence interval: 5.4-17.3), respectively, and odds ratio was 1.90 (95% confidence interval: 1.43-2.52, p  < 0.001). There was no difference in rates of major haemorrhage, odds ratio  = 1.01 (95% confidence interval: 0.61-1.69, p  = 0.966)., Conclusion: In patients with prior stroke, non-paroxysmal AF is associated with significantly higher risk of thromboembolic recurrence and mortality than paroxysmal AF. Although current guidelines make no distinction between non-paroxysmal AF and paroxysmal AF for secondary stroke prevention, future guidance and risk stratification tools may need to consider this differential risk (PROSPERO ID: CRD42019118531)., (© European Stroke Organisation 2020.)

Introduction: Approaches to economic evaluations of stroke therapies are varied and inconsistently described. An objective of the European Stroke Organisation (ESO) Health Economics Working Group is to standardise and improve the economic evaluations of interventions for stroke., Methods: The ESO Health Economics Working Group and additional experts were contacted to develop a protocol and a guidance document for data collection for economic evaluations of stroke therapies. A modified Delphi approach, including a survey and consensus processes, was used to agree on content. We also asked the participants about resources that could be shared to improve economic evaluations of interventions for stroke., Results: Of 28 experts invited, 16 (57%) completed the initial survey, with representation from universities, government, and industry. More than half of the survey respondents endorsed 13 specific items to include in a standard resource use questionnaire. Preferred functional/quality of life outcome measures to use for economic evaluations were the modified Rankin Scale (14 respondents, 88%) and the EQ-5D instrument (11 respondents, 69%). Of the 12 respondents who had access to data used in economic evaluations, 10 (83%) indicated a willingness to share data. A protocol template and a guidance document for data collection were developed and are presented in this article., Conclusion: The protocol template and guidance document for data collection will support a more standardised and transparent approach for economic evaluations of stroke care., (© European Stroke Organisation 2020.)

Introduction: Recent data suggest that statin use after intracerebral haemorrhage might be beneficial. However, data on the effects of early in-hospital statin exposure are lacking. Therefore, we sought to assess whether (1) early statin exposure during the acute phase after intracerebral haemorrhage and (2) early continuation of prevalent statin use are associated with favourable functional outcome., Patients and Methods: Data were obtained from the Virtual International Stroke Trials Archive. Patients were categorised according to use patterns of statins during this early in-hospital phase (continuation, discontinuation or new initiation of statins). Univariate and multivariable analyses were conducted to explore the association between early statin exposure and functional outcome., Results: A total of 919 patients were included in the analysis. Early in-hospital statin exposure (n = 89, 9.7%) was associated with better functional outcome (modified Rankin Scale ≤ 3) compared with 790 patients without statin exposure before or early after the event (66% versus 47%, adjusted OR 2.1, 95% confidence interval 1.3-3.6). Compared with patients without exposure to statins before and early after the event, early continuation of statin therapy (n = 57) was associated with favourable functional outcome (adjusted odds ratio 2.6, 95% confidence interval 1.3-5.2). The association between early continuation of statins and outcome remained robust in sensitivity analyses restricted to patients able to take oral medication within 72 h and one-week survivors., Discussion: It is possible that part of the observed associations are not due to a protective effect of statins but are confounded by indication bias., Conclusion: Statin exposure and continuation of prevalent statin therapy early after intracerebral haemorrhage are associated with favourable functional outcome after 90 days., (© European Stroke Organisation 2019.)

Background and Aims: The role of single pill combination therapy for stroke prevention remains to be established. We explored the perspectives of stroke survivors and healthcare professionals on single pill combination therapy for stroke prevention., Methods: We conducted focus groups involving stroke survivors and healthcare professionals., Results: We recruited six stroke survivors: four (67%) were female and mean age was 70 ± 12 years; and eight healthcare professionals (three Stroke Consultants, two Nurse Specialists, three General Practitioners). Improved adherence is the main perceived benefit of single pill combination therapy, although concerns exist surrounding less individualised care, unsuitability for use in the acute setting, reduced ability to titrate doses and difficulty identifying the cause of side effects. The clinical stability of patients, alongside single pill combination therapy efficacy, cost, side effect profile and evidence base for impact on risk factors and clinical outcomes are key factors influencing acceptability. Stroke survivors and healthcare professionals feel single pill combination therapy is most suitable for stable patients, although there is no evidence base for its use in this context., Conclusion: Stroke healthcare professionals and stroke survivors are most amenable to using single pill combination therapy for stable patients, although its role in this context should be evaluated in studies with risk factor targets and clinical outcomes as endpoints.

Background and Purpose- Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods- Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results- Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHA 2 DS 2 -VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHA 2 DS 2 -VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions- In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA 2 DS 2 -VASc score were associated with increased risk of cerebrovascular events.