Background: Benefits of endovascular thrombectomy (ET) after intravenous thrombolysis (IVT) for patients with acute ischaemic stroke (AIS) have been demonstrated, but analyses of the relationship... Show moreBackground: Benefits of endovascular thrombectomy (ET) after intravenous thrombolysis (IVT) for patients with acute ischaemic stroke (AIS) have been demonstrated, but analyses of the relationship between IVT-ET time delay and functional outcomes among patients receiving both treatments are lacking. Methods: We used data from the "Berlin-Specific Acute Treatment in Ischaemic and haemorrhAgic stroke with Long-term outcome" (B-SPATIAL) registry. Between January 1st, 2016 and December 31st, 2019, we included patients who received both IVT and ET. The primary outcome was the 3-month ordinal modified Rankin scale (mRS) score. The IVT-ET time delay was analyzed in categories and continuously. We used adjusted ordinal logistic regression to estimate common odds ratios (cOR) and 95% confidence intervals (CI). Secondary analyses involved flexible modeling of IVT-ET delay and dichotomous outcomes. Results: Of 11,049 patients, 714 who received IVT followed by ET were included. Compared with having an IVT-ET window >120 min (reference), for an IVT-ET window < 30 min, we obtained adjusted cORs for mRS of 0.41 (95% CI: 0.22 to 0.78); and 0.52 (95% CI: 0.33 to 0.82) for 30 to 120 min. Secondary analyses also found protective effects of shorter time delays against "poor" functional outcomes at 3 months. Conclusions: In patients with AIS, shorter IVT-ET intervals were associated with better 3-month functional outcomes. While the time-to-IVT and time-to-ET include the time until medical attention is received, the IVT-ET time delays fall entirely within the domain of medical management and thus might be easier to optimize. Show less
Early career researchers (ECRs) are important stakeholders leading efforts to catalyze systemic change in research culture and practice. Here, we summarize the outputs from a virtual unconventional... Show moreEarly career researchers (ECRs) are important stakeholders leading efforts to catalyze systemic change in research culture and practice. Here, we summarize the outputs from a virtual unconventional conference (unconference), which brought together 54 invited experts from 20 countries with extensive experience in ECR initiatives designed to improve the culture and practice of science. Together, we drafted 2 sets of recommendations for (1) ECRs directly involved in initiatives or activities to change research culture and practice; and (2) stakeholders who wish to support ECRs in these efforts. Importantly, these points apply to ECRs working to promote change on a systemic level, not only those improving aspects of their own work. In both sets of recommendations, we underline the importance of incentivizing and providing time and resources for systems-level science improvement activities, including ECRs in organizational decision-making processes, and working to dismantle structural barriers to participation for marginalized groups. We further highlight obstacles that ECRs face when working to promote reform, as well as proposed solutions and examples of current best practices. The abstract and recommendations for stakeholders are available in Dutch, German, Greek (abstract only), Italian, Japanese, Polish, Portuguese, Spanish, and Serbian. Show less
Objective To determine the role of circulating microvesicles (MV) on long-term cardiovascular outcomes after stroke, we measured them in patients with first-ever stroke with a 3-year follow-up.... Show moreObjective To determine the role of circulating microvesicles (MV) on long-term cardiovascular outcomes after stroke, we measured them in patients with first-ever stroke with a 3-year follow-up. Methods In the Prospective Cohort With Incident Stroke Berlin (PROSCIS-B), patients with first-ever ischemic stroke were followed up for 3 years. The primary combined endpoint consisted of recurrent stroke, myocardial infarction, and all-cause mortality. Citrate-blood levels of endothelial MV (EMV), leukocyte-derived MV (LMV), monocytic MV (MMV), and platelet-derived MV (PMV) were measured with flow cytometry. Kaplan-Meier curves and adjusted Cox proportional hazards models were used to estimate the effect of MV levels on the combined endpoint. Results Five hundred seventy-one patients were recruited (median age 69 years, 39% female, median NIH Stroke Scale score 2, interquartile range 1-4), and 95 endpoints occurred. Patients with levels of EMV (adjusted hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.2-4.9) or LMV (HR 3.1, 95% CI 1.4-6.8) in the highest quartile were more likely to experience an event than participants with lower levels with the lowest quartile used as the reference category. The association was less pronounced for PMV (HR 1.7, 95% CI 0.9-3.2) and absent for MMV (HR 1.1, 95% CI 0.6-1.8). Conclusion High levels of EMV and LMV after stroke were associated with worse cardiovascular outcome within 3 years. These results reinforce that endothelial dysfunction and vascular inflammation affect the long-term prognosis after stroke. EMV and LMV might play a role in risk prediction for stroke patients. ClinicalTrials.gov Identifier NCT01363856. Classification of Evidence This study provides Class II evidence of the effect of MV levels on subsequent stroke, myocardial infarction, or all-cause mortality in survivors of mild stroke. Show less
Ebinger, M.; Siegerink, B.; Kunz, A.; Wendt, M.; Weber, J.E.; Schwabauer, E.; ... ; Audebert, H.J. 2021
Importance Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been... Show moreImportance Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment. Objective To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only). Exposure Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794). Main Outcomes and Measures The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability. Results Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04). Conclusions and Relevance In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.This cohort study compares global disability at 3 months among Berlin patients with out-of-hospital ischemic stroke brought to care via a mobile stroke unit ambulance (with prehospital CT scanning with or without angiography, point-of-care laboratory testing, prehospital thrombolysis) vs conventional ambulance alone.Question Is the dispatch of mobile stroke units in the out-of-hospital setting before arriving at the hospital associated with better functional outcomes among patients with acute ischemic stroke eligible for thrombolysis or thrombectomy? Findings In this prospective nonrandomized controlled intervention study involving 1543 patients in Berlin, Germany, the dispatch of mobile stroke units in addition to conventional ambulances vs conventional ambulances alone was significantly associated with lower levels of global disability at 3 months (common odds ratio for higher modified Rankin Scale scores [ie, worse outcome], 0.71). Meaning Among patients with acute ischemic stroke in Berlin, Germany, dispatch of a mobile stroke unit was associated with lower global disability at 3 months; further research in diverse settings is needed. Show less
Background: Many regions worldwide reported a decline of stroke admissions during the early phase of the coronavirus disease 2019 (COVID-19) pandemic. It remains unclear whether urban and rural... Show moreBackground: Many regions worldwide reported a decline of stroke admissions during the early phase of the coronavirus disease 2019 (COVID-19) pandemic. It remains unclear whether urban and rural regions experienced similar declines and whether deviations from historical admission numbers were more pronounced among specific age, stroke severity or treatment groups.Methods: We used registry datasets from (a) nine acute stroke hospitals in Berlin, and (b) nine hospitals from a rural TeleNeurology network in Northeastern Germany for primary analysis of 3-week-rolling average of stroke/TIA admissions before and during the COVID-19 pandemic. We compared course of stroke admission numbers with regional cumulative severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) infections. In secondary analyses, we used emergency department logs of the Berlin Charite University hospital to investigate changes in age, stroke severity, and thrombolysis/thrombectomy frequencies during the early regional Sars-CoV-2 spread (March and April 2020) and compared them with preceding years.Results: Compared to past years, stroke admissions decreased by 20% in urban and 20-25% in rural hospitals. Deviations from historical averages were observable starting in early March and peaked when numbers of regional Sars-CoV-2 infections were still low. At the same time, average admission stroke severity and proportions of moderate/severe strokes (NIHSS >5) were 20 and 20-40% higher, respectively. There were no relevant deviations observed in proportions of younger patients (<65 years), proportions of patients with thrombolysis, or number of thrombectomy procedures. Stroke admissions at Charite subsequently rebounded and reached near-normal levels after 4 weeks when the number of new Sars-CoV-2 infections started to decrease.Conclusions: During the early pandemic, deviations of stroke-related admissions from historical averages were observed in both urban and rural regions of Northeastern Germany and appear to have been mainly driven by avoidance of admissions of mildly affected stroke patients. Show less
Rohmann, J.L.; Longstreth, W.T.; Cushman, M.; Fitzpatrick, A.L.; Heckbert, S.R.; Rice, K.; ... ; Siegerink, B. 2020
ObjectiveTo investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time.MethodsData from the... Show moreObjectiveTo investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time.MethodsData from the population-based Cardiovascular Health Study (n = 5,888, aged >= 65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function.ResultsAfter adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99-1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87-1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 beta = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 beta = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 beta = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 beta = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment.InterpretationThe results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses. Show less
Background Though risk for recurrent vascular events is high following ischemic stroke, little knowledge about risk factors for secondary events post-stroke exists. Objectives Coagulation factors... Show moreBackground Though risk for recurrent vascular events is high following ischemic stroke, little knowledge about risk factors for secondary events post-stroke exists. Objectives Coagulation factors XII, XI, and VIII (FXII, FXI, and FVIII) have been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke. Patients/Methods In the Prospective Cohort with Incident Stroke Berlin (PROSCIS-B) study, we followed participants aged 18 and older for 3 years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction, or all-cause mortality. We compared high coagulation factor activity levels to normal and low levels and also analyzed activities as continuous variables. We used Cox proportional hazards models adjusted for age, sex, and cardiovascular risk factors to estimate hazard ratios (HRs) for the combined endpoint. Results In total, 94 events occurred in 576 included participants, resulting in an absolute rate of 6.6 events per 100 person-years. After confounding adjustment, high FVIII activity showed the strongest relationship with the combined endpoint (HR = 2.05, 95% confidence interval [CI] 1.28-3.29). High FXI activity was also associated with a higher hazard (HR = 1.80, 95% CI 1.09-2.98), though high FXII activity was not (HR = 0.86, 95% CI 0.49-1.51). Continuous analyses yielded similar results. Conclusions In our study of mild to moderate ischemic stroke patients, high activity levels of FXI and FVIII but not FXII were associated with worse vascular outcomes in the 3-year period after first ischemic stroke. Show less
Meier, K.; Glatz, T.; Guijt, M.C.; Piccininni, M.; Meulen, M. van der; Atmar, K.; ... ; COVID 19 Survey Study Grp 2020
BackgroundThe extent to which people implement government-issued protective measures is critical in preventing further spread of coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2... Show moreBackgroundThe extent to which people implement government-issued protective measures is critical in preventing further spread of coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2. Our study aimed to describe the public belief in the effectiveness of protective measures, the reported implementation of these measures, and to identify communication channels used to acquire information on COVID-19 in European countries during the early stage of the pandemic.Methods and findingsAn online survey available in multiple languages was disseminated starting on March 19th, 2020. After five days, we computed descriptive statistics for countries with more than 500 respondents. Each day, we assessed enacted community containment measures by stage of stringency (I-IV). In total, 9,796 adults responded, of whom 8,611 resided in the Netherlands (stage III), 604 in Germany (stage III), and 581 in Italy (stage IV). To explore possible dynamics as containment strategies intensified, we also included 1,365 responses submitted during the following week. Participants indicated support for governmental measures related to avoiding social gatherings, selective closure of public places, and hand hygiene and respiratory measures (range for all measures: 95.0%-99.7%). Respondents from the Netherlands less frequently considered a complete social lockdown effective (59.2%), compared to respondents in Germany (76.6%) or Italy (87.2%). Italian residents applied enforced social distancing measures more frequently (range: 90.2%-99.3%, German and Dutch residents: 67.5%-97.0%) and self-initiated hygienic and social distancing behaviors (range: 36.3%-96.6%, German and Dutch residents: 28.3%-95.7%). Respondents reported being sufficiently informed about the outbreak and behaviors to avoid infection (range: 90.2%-91.1%). Information channels most commonly reported included television newspapers, official health websites, and social media. One week later, we observed no major differences in submitted responses.ConclusionsDuring the early stage of the COVID-19 pandemic, belief in the effectiveness of protective measures among survey respondents from three European countries was high and participants reported feeling sufficiently informed. In March 2020, implementation of measures differed between countries and were highest among respondents from Italy, who were subjected to the most stringent lockdown measures and greatest COVID-19 burden in Europe during this period. Show less
Background Cognitive and motor-performance decline with age and the process is accelerated by decline in general health. In this study, we aimed to estimate the effects of COPD and HB levels on... Show moreBackground Cognitive and motor-performance decline with age and the process is accelerated by decline in general health. In this study, we aimed to estimate the effects of COPD and HB levels on cognitive and motor performance in the general older population and assess potential interaction. Methods The English Longitudinal Study of Aging is a population-based cohort study including measurements of lung-function and HB levels together with cognitive and motor performance testing. Data were collected from 5709 participants including three measurement time over eight years. COPD was defined using lung-function-parameters and clinical symptoms. HB was assessed continuously and low HB was defined using clinical anemia cutoffs. Linear mixed-effects regression models were used to quantify the associations of COPD and HB with outcome measures, both individually and in combination. Results Participants with both low HB and COPD demonstrated worse motor performance compared to individuals with only one exposure, resulting in up to 1 s (95%CI, 0.04-1.8) longer time needed to complete the five times sit to stand task than what would be expected based on purely additive effects. Additionally in individuals with COPD, the time to complete the motor-performance task per unit decrease in continuous HB levels was longer than in participants without COPD after full adjustment for confounding (up to 1.38 s/unit HB level, 95% CI: 0.65-2.11). Conclusion In persons with COPD low HB levels may contribute to low motor-performance in a supra additive fashion. Further studies should re-evaluate whether earlier treatment of lower HB in these individuals might be beneficial. Show less
