| 1. |
- Ahmed, Niaz, et al.
(author)
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Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018.
- 2019
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In: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 4:4, s. 307-317
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Journal article (peer-reviewed)abstract
- The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at www.eso-karolinska.org and http://eso-stroke.org) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.
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| 2. |
- Sandset, Else Charlotte, et al.
(author)
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Women in the European Stroke Organisation : One, two, many… – A Top Down and Bottom Up approach
- 2019
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In: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 4:3, s. 247-253
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Journal article (peer-reviewed)abstract
- Background: An increasing proportion of physicians are women, yet they still face challenges with career advancement. In 2014, the European Stroke Organisation established the goal of increasing the number and participation of women within the society using a Top Down and Bottom Up approach. The ‘Women’s Initiative for Stroke in Europe’ was created the same year by a group of women active within the organisation. We aimed to assess the current status of women in European Stroke Organisation, and to explore the change in sex differences after the introduction of focused approaches to address disparities in 2014. Methods: Using organisational records, we collected data on sex differences in core activities from 2008 up to 2017 including membership, participation in conferences, courses and in the official journal of the society, and positions of seniority and leadership. We estimated sex distribution differences in each of the activities from 2014 to date. Results: In 2017, the proportion of female members was 40%, while 24% of fellows, 22% of the executive board and 19% of the editorial board in the official journal of the society were women. From 2014 to 2017, there was a significant increase in the proportion of female members (p = 0.0002) and in women participating in the annual conference as faculty (p = 0.001). There was no significant change in the sex distribution among the faculty members in junior educational activities (≤27%) or fellows. Interpretation: In 2017, the proportion of women holding positions of seniority and leadership is still significantly lower to the proportion of women attending educational activities. Transparent data on sex distribution will assist implementing tailored programmes to achieve progress against sex-based barriers.
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| 3. |
- Sharma, Mukul, et al.
(author)
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Safety and efficacy of factorXIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP) : a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial
- 2024
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In: LANCET NEUROLOGY. - 1474-4422 .- 1474-4465. ; 23:1, s. 46-59
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Journal article (peer-reviewed)abstract
- Background People with factor XI deficiency have lower rates of is chaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA).Methods AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose-response relationship with Multiple Comparison Procedure-Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19).Findings Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62-77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 168 (902% CI 145-191) for placebo, 167 (148-186) for 25 mg milvexian once daily, 166 (148-183) for 25 mg twice daily, 156 (139-175) for 50 mg twice daily, 154 (134-176) for 100 mg twice daily, and 153 (128-197) for 200 mg twice daily. No significant dose-response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 099 (902% CI 091-105) for 25 mg once daily, 099 (087-111) for 25 mg twice daily, 093 (078-111) for 50 mg twice daily, 092 (075-113) for 100 mg twice daily, and 091 (072-126) for 200 mg twice daily. No apparent dose-response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator.Interpretation Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA.
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| 5. |
- De Guio, François, et al.
(author)
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Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease
- 2016
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In: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X. ; 36:8, s. 1319-1337
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Research review (peer-reviewed)abstract
- Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.
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| 6. |
- Dichgans, Martin, et al.
(author)
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METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration : An initiative of the Joint Programme for Neurodegenerative Disease Research
- 2016
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In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 12:12, s. 1235-1249
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Journal article (peer-reviewed)abstract
- Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.
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| 7. |
- Jacob, Mina A, et al.
(author)
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Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults: A Worldwide Meta-analysis: The GOAL-Initiative.
- 2022
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In: Neurology. - 1526-632X. ; 98:6, s. e573-e588
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Journal article (peer-reviewed)abstract
- There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional healthcare services. To study the global distribution of risk factors, causes and 3-month mortality of young ischemic stroke patients, by performing a patient data meta-analysis form different cohorts worldwide.We did a pooled analysis of individual patient data from cohort studies which included consecutive ischemic stroke patients aged 18-50 years. We studied differences in prevalence of risk factors and causes between different ethnic and racial groups, geographic regions and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression.We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Blacks (hypertension, 52.1%; diabetes, 20.7%) and Asians (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often cause of stroke in high-income countries (HICs; both p<0.001), whereas ''other determined stroke'' and ''undetermined stroke'' were higher in low and middle-income countries (LMICs; both p<0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (OR 2.49; 95% CI 1.42-4.36).The ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial, and regional differences in incidence of ischemic stroke. Our results also visualize the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve healthcare facilities in LMICs.
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| 8. |
- Krzywicka, Katarzyna, et al.
(author)
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Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.
- 2023
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In: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 30:5, s. 1335-1345
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Journal article (peer-reviewed)abstract
- Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored.Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included.Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent.Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.
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| 9. |
- Norrving, Bo, et al.
(author)
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Action Plan for Stroke in Europe 2018–2030
- 2018
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In: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 3:4, s. 309-336
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Journal article (peer-reviewed)abstract
- Two previous pan-European consensus meetings, the 1995 and 2006 Helsingborg meetings, were convened to review the scientific evidence and the state of current services to identify priorities for research and development and to set targets for the development of stroke care for the decade to follow. Adhering to the same format, the European Stroke Organisation (ESO) prepared a European Stroke Action Plan (ESAP) for the years 2018 to 2030, in cooperation with the Stroke Alliance for Europe (SAFE). The ESAP included seven domains: primary prevention, organisation of stroke services, management of acute stroke, secondary prevention, rehabilitation, evaluation of stroke outcome and quality assessment and life after stroke. Research priorities for translational stroke research were also identified. Documents were prepared by a working group and were open to public comments. The final document was prepared after a workshop in Munich on 21–23 March 2018. Four overarching targets for 2030 were identified: (1) to reduce the absolute number of strokes in Europe by 10%, (2) to treat 90% or more of all patients with stroke in Europe in a dedicated stroke unit as the first level of care, (3) to have national plans for stroke encompassing the entire chain of care, (4) to fully implement national strategies for multisector public health interventions. Overall, 30 targets and 72 research priorities were identified for the seven domains. The ESAP provides a basic road map and sets targets for the implementation of evidence-based preventive actions and stroke services to 2030.
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| 10. |
- Sánchez Van Kammen, Mayte, et al.
(author)
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Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia
- 2021
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In: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 78:11, s. 1314-1323
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Journal article (peer-reviewed)abstract
- Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.Main Outcomes and Measures: Clinical characteristics and mortality rate.Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination..
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