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1.	Brauer, M, et al. (författare) Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021 2024 Ingår i: Lancet (London, England). - : Elsevier B.V.. - 1474-547X .- 0140-6736. ; 403:10440, s. 2162-2203 Tidskriftsartikel (refereegranskat)
2.	Forouzanfar, MH, et al. (författare) Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 388:10053, s. 1659-1724 Tidskriftsartikel (refereegranskat)
3.	Lim, SS, et al. (författare) Measuring the health-related Sustainable Development Goals in 188 countries: a baseline analysis from the Global Burden of Disease Study 2015 2016 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 388:10053, s. 1813-1850 Tidskriftsartikel (refereegranskat)
4.	Murray, CJL, et al. (författare) Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition 2015 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 386, s. 2145-2191 Tidskriftsartikel (refereegranskat)
5.	Naghavi, M, et al. (författare) Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021 2024 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 403:10440, s. 2100-2132 Tidskriftsartikel (refereegranskat)
6.	Dahlberg, Jonas, et al. (författare) Genetic variants in serum and glucocortocoid regulated kinase 1, a regulator of the epithelial sodium channel, are associated with ischaemic stroke. 2011 Ingår i: Journal of Hypertension. - 1473-5598. ; 29, s. 884-889 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Serum and glucocorticoid regulated kinase 1 (SGK1) expression is increased by aldosterone and is a key regulator of the amiloride-sensitive sodium channel (ENaC) in the distal nephron. We have previously shown that two SNPs in SGK1 (rs1057293 and rs1743966) are associated with blood pressure variation and blood pressure progression in the general population. Therefore, we tested the association of these variants with ischaemic stroke. METHODS: Using logistic regression, we analysed rs1057293 and rs1743966 for association with ischaemic stroke in two independent age-matched and sex-matched case-control groups from the twin cities of Lund (cases n = 1837 and controls n = 947) and Malmö (cases n = 888 and controls n = 893) in the Scania region of southern Sweden. RESULTS: In additive models adjusted for hypertension, smoking and diabetes, the major allele (G) of rs1057293 was associated (odds ratio, 95% confidence interval; P value) with ischaemic stroke with similar effect size in both studies; in Lund (1.35, 1.11-1.64; P = 0.002) and Malmö (1.30, 1.03-1.65; P = 0.027). When the two studies were pooled, the overall association was 1.32, 1.14-1.52; P < 0.001. The major allele of rs1743966 (A), which was in linkage disequilibrium with rs1057293, showed a similar trend as rs1057293 G-allele but with slightly weaker effect size and P value. CONCLUSION: In two independent but ethnically similar populations, we observed an association between genetic variants in SGK1 and ischaemic stroke. Interestingly, the association seems to be at least partially independent of blood pressure. This could imply that cerebrovascular ENaC or other SGK1-regulated proteins may be of importance for development of ischaemic stroke.
7.	Fava, Cristiano, et al. (författare) A genetic risk score for hypertension associates with the risk of ischemic stroke in a Swedish case-control study 2015 Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 23, s. 969-974 Tidskriftsartikel (refereegranskat)abstract Genetic risk scores (GRS), summing up the total effect of several single-nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS based on 29 SNPs discovered by genome-wide association studies and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other ‘traditional risk factors’, also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case–control study. Twenty-nine SNPs were genotyped in 3677 stroke cases and 2415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the combined sample, and separately for the three studies. After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the combined sample (OR (95% CI) 1.086 (1.029–1.147) per SD increase in the GRS P=0.003) with similar trends in all three samples: LSR (1.050 (0.967–1.140); P=0.25), MDC (1.168 (1.060–1.288); P=0.002) and SAHLSIS (1.124 (0.997–1.267); P=0.055). Measures of risk discrimination and reclassification improved marginally using the GRS. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case–control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.
8.	Feigin, VL, et al. (författare) Update on the Global Burden of Ischemic and Hemorrhagic Stroke in 1990-2013: The GBD 2013 Study 2015 Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 45:3, s. 161-176 Tidskriftsartikel (refereegranskat)abstract <b><i>Background:</i></b> Global stroke epidemiology is changing rapidly. Although age-standardized rates of stroke mortality have decreased worldwide in the past 2 decades, the absolute numbers of people who have a stroke every year, and live with the consequences of stroke or die from their stroke, are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care. <b><i>Objectives:</i></b> This study aims to estimate incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) for 188 countries from 1990 to 2013. <b><i>Methodology:</i></b> Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed, and all rates were age-standardized to a global population. All estimates were produced with 95% uncertainty intervals (UIs). <b><i>Results:</i></b> In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS) and 10.3 million new strokes (67% IS). Over the 1990-2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% (95% UI 3.11-4.00) and 9.66% (95% UI 8.47-10.70), respectively) to 2013 (4.62% (95% UI 4.01-5.30) and 11.75% (95% UI 10.45-13.31), respectively), but there was a diverging trend in developed and developing countries with a significant increase in DALYs and deaths in developing countries, and no measurable change in the proportional contribution of DALYs and deaths from stroke in developed countries. <b><i>Conclusion:</i></b> Global stroke burden continues to increase globally. More efficient stroke prevention and management strategies are urgently needed to halt and eventually reverse the stroke pandemic, while universal access to organized stroke services should be a priority.
9.	Ferrari, AJ, et al. (författare) Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021 2024 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 403:10440, s. 2133-2161 Tidskriftsartikel (refereegranskat)
10.	Gidlöf, Olof, et al. (författare) A Common Missense Variant in the ATP Receptor P2X7 Is Associated with Reduced Risk of Cardiovascular Events 2012 Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5 Tidskriftsartikel (refereegranskat)abstract Background and Purpose: Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic association studies. Methods: Two loss-of-function SNPs in P2RX7 were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals with cardiovascular risk factors. Eleven SNPs in a 250 kb region on chromosome 12 spanning P2RX7 as well as neighboring genes OASL, P2RX4 and CAMKK2 were genotyped in 4138 individuals with IS and 2528 controls. Association was examined using linear and logistic regression models with an additive genetic model. Results: The common loss-of-function variant rs3751143 was significantly associated with a decreased risk of IHD in smokers (P = 0.03) as well as decreased risk of IS (OR 0.89; 95% CI = 0.81-0.97; P = 0.012). In addition, an intronic SNP in CAMKK2, rs2686342, were associated with a decreased risk of IS (OR 0.89; 95% CI = 0.82-0.97; P = 0.011). In subgroup analyses, both SNPs were associated with decreased risk of IS in individuals with hypertension (P = 0.045 and 0.015, respectively). Conclusions: A common loss-of-function missense variant in the gene encoding the P2X7 receptor is associated with reduced risk of IS and with IHD in smokers. These findings might implicate a role of purinergic signaling in atherogenesis or atherothrombosis.
11.	Lindgren, Arne, et al. (författare) Clinical lacunar syndromes as predictors of lacunar infarcts. A comparison of acute clinical lacunar syndromes and findings on diffusion-weighted MRI 2000 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 101:2, s. 128-134 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To evaluate if patients with acute lacunar syndromes have acute lacunar infarcts or other types of cerebral lesions on diffusion-weighted MRI. METHODS: Patients with acute lacunar syndromes underwent echo-planar diffusion MRI of the brain within 3 days after stroke onset. Localization and size of lesions with hyperintense signal were determined, compared with clinical characteristics and with findings on follow-up T2-weighted MRI. RESULTS: Twenty-three patients participated in the study. Thirteen patients had pure motor stroke, 1 pure sensory stroke, 8 sensorimotor stroke, and 1 ataxic hemiparesis. Twenty-two patients had at least one lesion with increased signal on diffusion-weighted MR images. These acute lesions were in the internal capsule/ basal ganglia/thalamus in 13 patients, subcortical white matter in 5 patients, brainstem in 2 patients, cortex (multiple small lesions) in 1 patient, and cortex + basal ganglia in 1 patient. The median volume of the lesions was 0.6 ml on the initial examination and on follow-up, of 17 patients after 1 to 5 months, 0.5 ml. CONCLUSIONS: Almost all patients with acute ischemic lacunar syndromes have acute lesions on echo-planar diffusion-weighted MRI within 3 days after stroke onset. These lesions are mostly small and subcortical, compatible with lacunar infarcts caused by single penetrating artery occlusion, but in a minor proportion of patients (2 of 23 in our study) a cortical involvement is found.
12.	Lövkvist, Håkan, et al. (författare) A large-sample assessment of possible association between ischaemic stroke and rs12188950 in the PDE4D gene 2012 Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 20:7, s. 783-789 Tidskriftsartikel (refereegranskat)abstract Previous reports have shown ambiguous findings regarding the possible associations between ischaemic stroke (IS) and single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) gene region. The SNP rs12188950 (or SNP45) has often been studied in this context. We performed a multi-centre study involving a large sample of 2599 IS patients and 2093 control subjects from the south and west regions of Sweden to replicate previous studies regarding IS risk and rs12188950. Subjects from Lund Stroke Register (LSR), Malmo Diet and Cancer Study (MDC) and Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) were enroled. Subgroups of participants with hypertension and participants <55 years of age, as well as the TOAST subgroups large vessel disease, small vessel disease and cardioembolism, were also assessed. Univariate odds ratios (ORs) and ORs controlling for hypertension, diabetes and current smoking were calculated. We additionally performed a meta-analysis including 10 500 patients and 10 102 control subjects from 17 publications (including the present study). When assessing pooled data from LSR, MDC and SAHLSIS we obtained no association between IS and rs12188950 for all participants (OR=0.93; 95% confidence interval (CI): 0.83-1.05). Significant associations were not found for hypertensive participants or participants with age <55, or when separately evaluating patients from the three different TOAST subgroups. The meta-analysis showed no significant overall estimate (OR=0.96; 95% CI: 0.89-1.04) with significant heterogeneity for random effect (P=0.042). No effect from rs12188950 on IS was found from either our pooled multi-centre data or the performed meta-analysis. We did not find any association between the examined subgroups and rs12188950 either. European Journal of Human Genetics (2012) 20, 783-789; doi: 10.1038/ejhg.2012.4; published online 25 January 2012
13.	Lövkvist, Håkan, et al. (författare) Are 25 SNPs from the CARDIoGRAM study associated with ischaemic stroke? 2013 Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101. ; 20:9, s. 1284-1291 Tidskriftsartikel (refereegranskat)abstract Background and purpose: The Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Study (CARDIoGRAM) reported 25 single-nucleotide polymorphisms (SNPs) on 15 chromosomes to be associated with coronary artery disease (CAD) risk. Because common vascular risk factors are shared between CAD and ischaemic stroke (IS), these SNPs may also be related to IS overall or one or more of its pathogenetic subtypes. Methods: We performed a candidate gene study comprising 3986 patients with IS and 2459 control subjects. The 25 CAD-associated SNPs reported by CARDIoGRAM were examined by allelic association analysis including logistic regression. Weighted and unweighted genetic risk scores (GRSs) were also compiled and likewise analysed against IS. We furthermore considered the IS main subtypes large-vessel disease (LVD), small-vessel disease and cardioembolic stroke [according to Trial of Org 10172 in Acute Stroke Treatment (TOAST)] separately. Results: SNP rs4977574 on chromosome 9p21.3 was associated with overall IS [odds ratio (OR) = 1.12; 95% confidence interval (CI): 1.04-1.20; P = 0.002] as well as LVD (OR = 1.36; 95% CI: 1.13-1.64; P = 0.001). No other SNP was significantly associated with IS or any of its main subtypes. Analogously, the GRSs did not show any noticeable effect. Conclusions: Besides the previously reported association with SNPs on chromosome 9p21, this study did not detect any significant association between IS and CAD-susceptible genetic variants. Also, GRSs compiled from these variants did not predict IS or any pathogenetic IS subtype, despite a total sample size of 6445 participants.
14.	Marini, S., et al. (författare) Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis 2019 Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:4, s. 480-491 Tidskriftsartikel (refereegranskat)abstract IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
15.	Meretoja, Atte, et al. (författare) Stroke doctors : Who are we? A World Stroke Organization survey 2017 Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4949 .- 1747-4930. ; 12:8, s. 858-868 Tidskriftsartikel (refereegranskat)abstract Background Specialist training provides skilled workforce for service delivery. Stroke medicine has evolved rapidly in the past years. No prior information exists on background or training of stroke doctors globally. Aims To describe the specialties that represent stroke doctors, their training requirements, and the scientific organizations ensuring continuous medical education. Methods The World Stroke Organization conducted an expert survey between June and November 2014 using e-mailed questionnaires. All Organization for Economic Co-operation and Development countries with >1 million population and other countries with >50 million population were included ( n = 49, total 5.6 billion inhabitants, 85% of global strokes). Two stroke experts from each selected country were surveyed, discrepancies resolved, and further information on identified stroke-specific curricula sought. Results We received responses from 48 (98%) countries. Of ischemic stroke patients, 64% were reportedly treated by neurologists, ranging from 5% in Ireland to 95% in the Netherlands. Per thousand annual strokes there were average six neurologists, ranging from 0.3 in Ethiopia to 33 in Israel. Of intracerebral hemorrhage patients, 29% were reportedly treated by neurosurgeons, ranging from 5% in Sweden to 79% in Japan, with three neurosurgeons per thousand strokes, ranging from 0.1 in Ethiopia to 24 in South Korea. Most countries had a stroke society (86%) while only 10 (21%) had a degree or subspecialty for stroke medicine. Conclusions Stroke doctor numbers, background specialties, and opportunities to specialize in stroke vary across the globe. Most countries have a scientific society to pursue advancement of stroke medicine, but few have stroke curricula.
16.	Nordanstig, Annika, 1974, et al. (författare) Evaluation of the Swedish National Stroke Campaign : A population-based time-series study 2019 Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 14:9, s. 862-870 Tidskriftsartikel (refereegranskat)abstract Background: Time delay from stroke onset to hospital arrival is an important obstacle to recanalization therapy. To increase knowledge about stroke symptoms and potentially reduce delayed hospital arrival, a 27-month national public information campaign was conducted in Sweden. Aim: To assess the effects of a national stroke campaign in Sweden. Methods: This nationwide study included 97,840 patients with acute stroke, admitted to hospital and registered in the Swedish Stroke Register from 1 October 2010 to 31 December 2014 (one year before the campaign started to one year after the campaign ended). End points were (1) proportion of patients arriving at hospital within 3 h of stroke onset and (2) the proportion < 80 years of age receiving recanalization therapy. Results: During the campaign, both the proportion of patients arriving at hospital within 3 h (p < 0.05) and the proportion receiving recanalization therapy (p < 0.001) increased. These proportions remained stable the year after the campaign, and no significant improvements with respect to the two end points were observed during the year preceding the campaign. In a multivariable logistic regression model comparing the last year of the campaign with the year preceding the campaign, the odds ratio of arriving at hospital within 3 h was 1.05 (95% confidence interval (CI): 1.00–1.09) and that of receiving recanalization was 1.34 (95% CI: 1.24–1.46). Conclusion: The Swedish National Stroke Campaign was associated with a sustained increase in the proportion of patients receiving recanalization therapy and a small but significant improvement in the proportion arriving at hospital within 3 h.
17.	Norrving, Bo, et al. (författare) Prognosis of patients with lacunar infarction syndromes 2002 Ingår i: Subcortical stroke. - 9780192631572 ; , s. 297-297 Bokkapitel (övrigt vetenskapligt/konstnärligt)
18.	Smith, Gustav, et al. (författare) Common Genetic Variants on Chromosome 9p21 Confers Risk of Ischemic Stroke A Large-Scale Genetic Association Study 2009 Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 2:2, s. 159-164 Tidskriftsartikel (refereegranskat)abstract Background-Epidemiological studies indicate a genetic contribution to ischemic stroke risk, but specific genetic variants remain unknown, with the exception of a few rare variants. Recent genome-wide association studies identified and replicated common genetic variants on chromosome 9p21 to confer risk of coronary heart disease. We examined whether these variants are associated with ischemic stroke. Methods and Results-We genotyped 6 common genetic variants on chromosome 9p21, previously associated with coronary artery disease in genome-wide association studies, in 2 population-based studies in southern Sweden, the Lund Stroke Register (n = 1837 cases, 947 controls) and the Malmo Diet and Cancer study (MDC; n = 888 cases, 893 controls). We examined association in each study and in the pooled dataset. Adjustments were made for cardiovascular risk factors and further for previous myocardial infarction in MDC. We found a modest increase in ischemic stroke risk for 2 common (minor allele frequencies 0.46 to 0.49) variants, rs2383207 (P = 0.04 in Lund Stroke Register, P = 0.01 in MDC) and rs10757274 (P = 0.03 in Lund Stroke Register, P = 0.03 in MDC), in each sample independently. The strength of the association increased when samples were pooled with an odds ratio of 1.15 (95% CI, 1.05 to 1.25; P = 0.002) for the strongest variant rs2383207. Results were similar after adjustment for clinical covariates. rs1333049 also showed significant association in MDC, which increased in the pooled sample (P = 0.004). Conclusions-In this large sample (n = 4565), we detected common genetic determinants for ischemic stroke on chromosome 9p21. Our findings indicate that ischemic stroke shares pathophysiological determinants with coronary heart disease and other arterial diseases and highlight the need for large sample sizes in stroke genetics. (Circ Cardiovasc Genet. 2009; 2: 159-164.)
19.	Staaf, Gert, et al. (författare) Diffusion-weighted MRI findings in patients with capsular warning syndrome 2004 Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 17:1, s. 1-8 Tidskriftsartikel (refereegranskat)abstract Background and Purpose: The 'capsular warning syndrome' (CWS) of recurrent stereotyped episodes of motor or sensory dysfunction is clinically well recognized, and is associated with a high risk of imminent lacunar infarction with permanent deficits resembling those of CWS. However, the pathophysiology of CWS has not been well characterized. We report a clinicoanatomic correlation with MR imaging studies in the acute and chronic phases in patients with CWS. Material and Methods: Between April 1997 and March 2001, we prospectively studied 8 patients, mean age 73.3 years, presenting with 4 - 17 motor or sensorimotor transient ischemic attacks ( TIAs; duration 2 - 90 min) up to 3 days after onset of the first episode. Four patients were free of symptoms between the attacks and had no residua, whereas 4 patients developed a pure motor or sensorimotor stroke within 1 - 3 days after symptom onset. Diffusion-weighted echoplanar MRI (DWI) and T-2-weighted MRI studies were performed within 1 week after symptom onset and were repeated 1 - 2 months later. Results: Seven of the 8 patients had an appropriate lesion on DWI in the acute phase. DWI abnormalities in the 3 patients with TIAs were 4 - 10 mm in diameter and confined to the lateral thalamus or medial globus pallidus without involving the internal capsule, whereas 4 patients who developed a stroke had abnormalities localized to the putamen extending to corona radiata ( 3 patients), or the pontomesencephalic junction ( 1 patient). All 6 patients who underwent follow-up MRI had an infarct on T-2-weighted images corresponding to, but usually smaller than, the acute phase DWI abnormality. Conclusions: Small infarcts in the basal ganglia or the pons, close to central motor pathways, appear to be the primary lesion in CWS. The pathophysiology of CWS is complex, and may involve hemodynamic mechanisms in penetrating arterial territories, as well as molecular mechanisms, such as peri-infarct depolarizations affecting adjacent motor pathways. Copyright (C) 2004 S. Karger AG, Basel.
20.	Vos, T, et al. (författare) Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 388:10053, s. 1545-1602 Tidskriftsartikel (refereegranskat)
21.	Abbafati, C, et al. (författare) Five insights from the Global Burden of Disease Study 2019 2020 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 396:10258, s. 1135-1159 Tidskriftsartikel (refereegranskat)
22.	Aguiar de Sousa, Diana, et al. (författare) Delivery of acute ischaemic stroke treatments in the European region in 2019 and 2020 2023 Ingår i: European Stroke Journal. - 2396-9873. ; 8:3, s. 618-628 Tidskriftsartikel (refereegranskat)abstract Introduction: We assessed best available data on access and delivery of acute stroke unit (SU) care, intravenous thrombolysis (IVT) and endovascular treatment (EVT) in the European region in 2019 and 2020. Patients and methods: We compared national data per number of inhabitants and per 100 annual incident first-ever ischaemic strokes (AIIS) in 46 countries. Population estimates and ischaemic stroke incidence were based on United Nations data and the Global Burden of Disease Report 2019, respectively. Results: The estimated mean number of acute SUs in 2019 was 3.68 (95% CI: 2.90–4.45) per one million inhabitants (MIH) with 7/44 countries having less than one SU per one MIH. The estimated mean annual number of IVTs was 21.03 (95% CI: 15.63–26.43) per 100,000 and 17.14% (95% CI: 12.98–21.30) of the AIIS in 2019, with highest country rates at 79.19 and 52.66%, respectively, and 15 countries delivering less than 10 IVT per 100,000. The estimated mean annual number of EVTs in 2019 was 7.87 (95% CI: 5.96–9.77) per 100,000 and 6.91% (95% CI: 5.15–8.67) of AIIS, with 11 countries delivering less than 1.5 EVT per 100,000. Rates of SUs, IVT and EVT were stable in 2020. There was an increase in mean rates of SUs, IVT and EVT compared to similar data from 2016. Conclusion: Although there was an increase in reperfusion treatment rates in many countries between 2016 and 2019, this was halted in 2020. There are persistent major inequalities in acute stroke treatment in the European region. Tailored strategies directed to the most vulnerable regions should be prioritised.
23.	Aguilar, Maria I., et al. (författare) Treatment of warfarin-associated intracerebral hemorrhage: Literature review and expert opinion 2007 Ingår i: Mayo Clinic Proceedings. - 0025-6196. ; 82:1, s. 82-92 Forskningsöversikt (refereegranskat)abstract Wider use of oral anticoagulants has led to an increasing frequency of warfarin-related intracerebral hemorrhage (ICH). The high early mortality of approximately 50% has remained stable in recent decades. In contrast to spontaneous ICH, the duration of bleeding is, 12 to 24 hours in many patients, offering a longer opportunity for Intervention. Treatment varies widely, and optimal therapy has yet to be defined. An OVID search was conducted from January 1996 to January 2006, combining the terms warfarin or anticoagulation with intracranial hemorrhage or intracerebral hemorrhage. Seven experts on clinical stroke, neurologic intensive care, and hematology were provided with the available information and were asked to independently address 3 clinical scenarios about acute reversal and resumption of anticoagulation in the setting of warfarin-associated ICH. No randomized trials assessing clinical outcomes were found on management of warfarin-associated ICH. All experts agreed that anticoagulation should be urgently reversed, but how to achieve it varied from use of prothrombin complex concentrates only (3 experts) to recombinant factor Vila only (2 experts) to recombinant factor Vila along with fresh frozen plasma (1 expert) and prothrombin complex concentrates or fresh frozen plasma (1 expert). All experts favored resumption of warfarin therapy within 3 to 10 days of ICH in stable patients in whom subsequent anticoagulation is mandatory. No general agreement occurred regarding subsequent anticoagulation of patients with atrial fibrillation who survived warfarin-associated ICH. For warfarin-associated ICH, discontinuing warfarin therapy with administration of vitamin K does not reverse the hemostatic defect for many hours and is inadequate. Reasonable management based on expert opinion includes a wide range of additional measures to reverse anticoagulation in the absence of solid evidence.
24.	Aigner, Annette, et al. (författare) Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young Adults 2017 Ingår i: Stroke. - 0039-2499. ; 48:7, s. 1744-1751 Tidskriftsartikel (refereegranskat)abstract Background and Purpose - As stroke in young adults is assumed to have different etiologies and risk factors than in older populations, the aim of this study was to examine the contribution of established potentially modifiable cardiovascular risk factors to the burden of stroke in young adults. Methods - A German nationwide case-control study based on patients enrolled in the SIFAP1 study (Stroke In Young Fabry Patients) 2007 to 2010 and controls from the population-based GEDA study (German Health Update) 2009 to 2010 was performed. Cases were 2125 consecutive patients aged 18 to 55 years with acute first-ever stroke from 26 clinical stroke centers; controls (age- and sex-matched, n=8500, without previous stroke) were from a nationwide community sample. Adjusted population-attributable risks of 8 risk factors (hypertension, hyperlipidemia, diabetes mellitus, coronary heart disease, smoking, heavy episodic alcohol consumption, low physical activity, and obesity) and their combinations for all stroke, ischemic stroke, and primary intracerebral hemorrhage were calculated. Results - Low physical activity and hypertension were the most important risk factors, accounting for 59.7% (95% confidence interval, 56.3-63.2) and 27.1% (95% confidence interval, 23.6-30.6) of all strokes, respectively. All 8 risk factors combined explained 78.9% (95% confidence interval, 76.3-81.4) of all strokes. Population-attributable risks of all risk factors were similar for all ischemic stroke subtypes. Population-attributable risks of most risk factors were higher in older age groups and in men. Conclusions - Modifiable risk factors previously established in older populations also account for a large part of stroke in younger adults, with 4 risk factors explaining almost 80% of stroke risk.
25.	Aked, Joseph, et al. (författare) Attitudes to Stem Cell Therapy among Ischemic Stroke Survivors in the Lund Stroke Recovery Study 2017 Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 26:8, s. 566-572 Tidskriftsartikel (refereegranskat)abstract Preclinical studies suggest that stem cell therapy (SCT) may improve poststroke recovery, and clinical trials investigating safety are ongoing. However, knowledge about patients' attitudes to SCT in stroke is limited. We evaluated the knowledge and attitudes to this therapeutic approach as well as possible factors influencing this among stroke patients potentially suitable for SCT. Consecutive first-ever acute ischemic stroke patients aged 20-75 years with NIH stroke scale scores 1-18 were included. Exclusion criteria were severe comorbidities or infratentorial stroke. Clinical follow-up after 3-5 years assessed severity of residual stroke symptoms, cognitive function, functional status, patient-reported outcome, and comorbidity, and after receiving standardized information, the participants also completed an eight-item questionnaire on knowledge and attitudes about SCT. The relationships between clinical variables and positive attitude to SCT were assessed with logistic regression analyses. Of 108 patients included at baseline, 84 participated at follow-up and completed the questionnaire. In total, 12% had prior knowledge of SCT. When informed, 63% were positive toward it and 36% reported willingness to participate in SCT trials. Only 5%-8% expressed ethical considerations regarding different stem cell sources. Positive attitudes to SCT were associated with male gender (OR: 3.74; 95% CI: 1.45-9.61; P < 0.01) and better patient-reported outcome (OR: 1.02; 95% CI: 1.00-1.04; P < 0.05). In conclusion, stroke patients had limited prior knowledge of SCT, yet attitudes were positive among the majority after receiving standardized and neutral information. Gender and degree of stroke recovery may influence attitudes to SCT, indicating a need for targeted information to improve knowledge about SCT.
26.	Aked, Joseph, et al. (författare) Completeness of case ascertainment in Swedish hospital-based stroke registers 2020 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 141:2, s. 148-155 Tidskriftsartikel (refereegranskat)abstract Background: There is a worldwide development toward using data from hospital-based stroke registers to estimate epidemiological trends. However, incomplete case ascertainment may cause selection bias. We examined the completeness of case ascertainment and selection bias in two hospital-based Swedish stroke registers. Methods: First-ever stroke cases between March 2015 and February 2016 in the catchment area of Skåne University Hospital, Lund, Sweden, were included from multiple overlapping sources: two hospital-based stroke registers, Riksstroke-Lund and Lund Stroke Register (LSR); local outpatient and inpatient registers; primary care registers; and autopsy registers. The resulting population-based cohort was used as reference to assess completeness of case ascertainment and patient characteristics in Riksstroke-Lund and LSR. Results: In total, 400 stroke patients were identified. Riksstroke-Lund detected 328 (82%) patients, whereas LSR detected 363 (91%). Patients undetected by hospital-based registers had higher 28-day case fatality than those detected (44% vs 9%; P =.001). Patients only detected in primary care (n = 11) more often lived in healthcare facilities compared with those detected by hospital-based registers (57% vs 7%; P =.001). Patients not detected by Riksstroke-Lund, but detected by population-based sources, had less severe strokes (median NIHSS 3 vs 5; P =.013). Conclusions: Some first-ever stroke patients, such as those with high early case fatality and those with mild stroke, may go undetected with hospital-based screening used in clinical stroke registers. This can result in selection bias due to not identifying specific groups of patients including some with high early case fatality and those living in healthcare facilities.
27.	Aked, Joseph, et al. (författare) Temporal Trends of Stroke Epidemiology in Southern Sweden : A Population-Based Study on Stroke Incidence and Early Case-Fatality 2018 Ingår i: Neuroepidemiology. - : S. Karger AG. - 0251-5350 .- 1423-0208. ; 50:3-4, s. 174-182 Tidskriftsartikel (refereegranskat)abstract Background: Up-to-date epidemiological stroke studies are important for healthcare planning and evaluating prevention strategies. This population-based study investigates temporal trends in stroke incidence and case-fatality in southern Sweden. Methods: First-ever stroke cases in the local catchment area of Skåne University Hospital in Lund, Sweden, between March, 2015 and February, 2016, were included from several sources, including 2 prospective hospital-based registers, retrospective screening of primary care visits, and autopsy registers. Stroke incidence and 28-day case-fatality rates were compared with data from this area obtained through similar methodology between March, 2001 and February, 2002. Results: Altogether, 456 and 413 first-ever stroke patients were identified during the earlier and later time periods respectively. The age- and sex-standardized stroke incidence rates decreased from 246 (95% CI 224–270) to 165 (95% CI 149–182) per 100,000 people. However, incidence remained unaltered among those <65 years. Early case-fatality decreased from 14 to 11% (p = 0.165). Conclusion: First-ever stroke incidence in southern Sweden has decreased to 33% since the beginning of this millennium. Incidence rates have decreased among the elderly but remain unchanged among younger age groups. Our findings warrant further studies on trends in risk factor profiles and effects of prevention strategies, and heightened focus on stroke in the young.
28.	Alexandrov, Andrei V., et al. (författare) Suggestions for Reviewing Manuscripts 2009 Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 28:3, s. 243-246 Tidskriftsartikel (refereegranskat)abstract Background: Scientific reviewing is a voluntary process to determine if a manuscript deserves publication. REVIEW means: Responsibly Evaluate, Verify and Improve the manuscript, Educate the authors and editors, and Weigh your expert opinion against the submitted work. Provide your review in a respectful, unbiased and timely manner. Review Methods: Make sure editors know about your willingness to review and your particular area(s) of expertise. If you find yourself in a conflict of interest, decline to participate in reviewing. If you accept, complete reviews on time. Determine and rate (1) the methodological validity, (2) originality, (3) significance of findings, (4) the style and clarity of presentation and (5) the findings' interest to the readership of the journal for which you are asked to review a manuscript. Specifically evaluate (6) if the results support any claims or conclusions made and, most importantly, (7) if the abstract correctly reflects the full content of a manuscript. Summarize your review in specific comments to the authors. Make recommendations whether to accept, revise or reject the manuscript to the editor only. Review Results: Start with a brief summary of the manuscript's subject, strengths and key findings/claims. Present your specific criticisms and suggestions in numbered lists for the authors to address. Never use demeaning and offensive words or sarcasm since, in the first place, this reflects upon your own ethics and integrity as well as upon the journal's. Use a constructive tone, and if you see any deficiencies, educate the authors in a respectful manner so that, even if a manuscript is rejected, they will learn from you, improve the manuscript or conduct a better study in the future. Also include ratings from 1 to 7 in your comments to the authors, as far as they are relevant and may explain your final decision. Conclusions: Judge others as you would like to be judged yourself. We hope these suggestions serve to help new reviewers and refresh the willingness of battle-hardened veterans to continuously serve the medical literature. Copyright (C) 2009 S. Karger AG, Basel
29.	Anderson, Christopher D., et al. (författare) Common Variants Within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage 2013 Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 44:3, s. 612-619 Tidskriftsartikel (refereegranskat)abstract Background and Purpose-Previous studies demonstrated association between mitochondrial DNA variants and ischemic stroke (IS). We investigated whether variants within a larger set of oxidative phosphorylation (OXPHOS) genes encoded by both autosomal and mitochondrial DNA were associated with risk of IS and, based on our results, extended our investigation to intracerebral hemorrhage (ICH). Methods-This association study used a discovery cohort of 1643 individuals, a validation cohort of 2432 individuals for IS, and an extension cohort of 1476 individuals for ICH. Gene-set enrichment analysis was performed on all structural OXPHOS genes, as well as genes contributing to individual respiratory complexes. Gene-sets passing gene-set enrichment analysis were tested by constructing genetic scores using common variants residing within each gene. Associations between each variant and IS that emerged in the discovery cohort were examined in validation and extension cohorts. Results-IS was associated with genetic risk scores in OXPHOS as a whole (odds ratio [OR], 1.17; P=0.008) and complex I (OR, 1.06; P=0.050). Among IS subtypes, small vessel stroke showed association with OXPHOS (OR, 1.16; P=0.007), complex I (OR, 1.13; P=0.027), and complex IV (OR, 1.14; P=0.018). To further explore this small vessel association, we extended our analysis to ICH, revealing association between deep hemispheric ICH and complex IV (OR, 1.08; P=0.008). Conclusions-This pathway analysis demonstrates association between common genetic variants within OXPHOS genes and stroke. The associations for small vessel stroke and deep ICH suggest that genetic variation in OXPHOS influences small vessel pathobiology. Further studies are needed to identify culprit genetic variants and assess their functional consequences. (Stroke. 2013;44:612-619.)
30.	Anderson, Christopher D., et al. (författare) Genetic variants in CETP increase risk of intracerebral hemorrhage 2016 Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 80:5, s. 730-740 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH.METHODS: We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk.RESULTS: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10(-4) ) with no heterogeneity across studies (I(2) = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10(-6) ).INTERPRETATION: Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.
31.	Andgren, S, et al. (författare) Time delay between symptom and surgery in patients with carotid artery stenosis. 2011 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 124, s. 329-333 Tidskriftsartikel (refereegranskat)abstract Andgren S, Sjöberg L, Norrving B, Lindgren A. Time delay between symptom and surgery in patients with carotid artery stenosis. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01478.x. © 2011 John Wiley & Sons A/S. Objectives - Many severe strokes are preceded by warning signs such as a transient ischemic attack or stroke with minor deficits. Carotid endarterectomy (CEA) of a symptomatic carotid artery stenosis can prevent future strokes, but should be performed within 2 weeks after the initial symptom to maximize the benefit. The aim of this study was to determine the time delays between symptom and CEA. Methods- We performed a single center observational retrospective study at a tertiary stroke center. A total of 142 carotids in 139 patients with symptomatic stenoses between 2002 and 2006 were included. The main outcome measure was time between qualifying cerebrovascular symptom and CEA. Results - The median time between symptom and CEA was 26 days. The longest delays were between the last diagnostic examination and carotid conference, and between carotid conference and surgery. The median time was shorter for those who received emergency medical care (median 21 days) and for those who were admitted immediately to hospital (median 20 days). Conclusions - The time between symptom and surgery is often longer than desirable. There are several measures to improve the chain of procedures for patients with carotid artery stenosis. These may include omitting the formal carotid conference for uncomplicated cases and minimizing waiting time for surgery.
32.	Andsberg, Gunnar, et al. (författare) PreHospital Ambulance Stroke Test : pilot study of a novel stroke test 2017 Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - London, UK : BioMed Central. - 1757-7241. ; 25:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: There is a need for a prehospital stroke test that in addition to high sensitivity for stroke, also is able to communicate stroke severity similar to the National Institute of Health Stroke Scale (NIHSS).METHODS: The PreHospital Ambulance Stroke Test (PreHAST), an eight item test based on NIHSS, which scores stroke severity from 0-19 points, was designed and adapted for the ambulance services. In the pilot study the ambulance nurses used PreHAST to assess patients with suspected stroke in the prehospital setting. Regardless of the results after PreHAST testing the patients were triaged with a provisional stroke diagnosis. The PreHAST scores were compared with the final diagnosis and the ability to differentiate stroke and transient ischemic attacks (TIA) with ongoing symptoms at evaluation from non-stroke patients was analysed.RESULTS: 69 patients were included in the study, 26 had stroke/TIA and 43 other diagnoses. All stroke/TIA patients were identified by PreHAST (sensitivity 100% (95% CI; 87-100%)). The specificity increased with higher PreHAST scores and the discriminative capacity for PreHAST for different cut off values showed an area under the curve of 0.77 (95%CI; 0.66-0.88) in the receiver operating characteristic (ROC) analysis.DISCUSSION: PreHAST is designed for high sensitivity, screening for a broad range of stroke symptoms including most key components of NIHSS. The promising sensitivity between 87 and 100% in our study has to be confirmed in a larger study also including multiple centres. Higher PreHAST scores implied more typical patterns of stroke and accordingly the proportion of stroke mimics decrease with higher scores. However, also stroke mimics with epilepsy/seizure and patients with deficit after prior stroke could show higher PreHAST scores. Other prehospital stroke tests that evaluate stroke severity have been designed with the main purpose to screen for large vessel occlusion. The advantage of PreHAST is the dual purpose not only to evaluate stroke severity but also to screen for stroke in general.CONCLUSIONS: PreHAST is a new screening test of stroke adapted for ambulance services that in addition to high sensitivity for stroke, provides a grading system with increasing specificity with higher scores.
33.	Apostolaki-Hansson, Trine, et al. (författare) Diverging Trends in Survival and Functional Outcome between Males and Females after Intracerebral Hemorrhage Ingår i: Neuroepidemiology. - 1423-0208. ; , s. 1-11 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Compared to ischemic stroke, sex differences in patient outcomes following intracerebral hemorrhage (ICH) are underreported. We aimed to determine sex differences in mortality and functional outcomes in a large, unselected Swedish cohort.METHODS: In this observational study, data on 22,789 patients with spontaneous ICH registered in the Swedish Stroke Register between 2012 and 2019 were used to compare sex differences in 90-day mortality and functional outcome using multivariable Cox and logistic regression analyses, adjusting for relevant confounders. Multiple imputation was used to impute missing data.RESULTS: The crude 90-day mortality rate was 36.7% in females (3,820/10,405) and 31.7% in males (3,929/12,384) (female hazard ratio [HR] 1.20 95% confidence interval [CI]: 1.15-1.25). In multivariable analysis, the HR for 90-day mortality following ICH in females was 0.89 (95% CI: 0.85-0.94). Age was an important driving factor for the effect of sex on mortality. After adjustment for age, vascular risk factors, and stroke severity, the 90-day functional outcome in pre-stroke independent patients was worse in females compared to males (odds ratio: 1.27 95% CI: 1.16-1.40).CONCLUSION: In this large observational study, despite lower 90-day mortality, the female sex was independently associated with a worse functional outcome compared to males after ICH, even after adjusting for significant covariates. These diverging trends have not been previously reported for ICH. Given the observational design, our findings should be interpreted with caution, thus further external validation is warranted.
34.	Apostolaki-Hansson, Trine, et al. (författare) Patient factors associated with receiving reversal therapy in oral anticoagulant-related intracerebral hemorrhage 2022 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 146:5, s. 590-597 Tidskriftsartikel (refereegranskat)abstract Background: We aimed to describe baseline characteristics of patients with oral anticoagulant-related intracerebral hemorrhage (OAC-ICH) in Sweden and to identify predictive variables associated with receiving hemostatic treatment in the event of OAC-ICH. Methods: We performed an observational study based on data from Riksstroke and the Swedish Causes of Death Register to define baseline characteristics of patients with OAC-ICH who received reversal treatment compared with patients who did not receive reversal treatment during 2017–2019. Predictive analysis was performed using multivariable logistic regression to identify odds ratios for factors associated with receiving OAC reversal treatment. Results: We included 1902 patients ((n = 1146; OAC reversal treatment) (n = 756; no OAC reversal treatment)). The proportion of non-Vitamin K oral anticoagulant associated ICH (NOAC-ICH) patients who received reversal treatment was 48.4% and the proportion of Vitamin K antagonist-associated ICH (VKA-ICH) patients was 72.9%. Factors associated with a lower odds of receiving reversal treatment were increased age (OR = 0.98; 95% CI: 0.96–0.99), previous stroke (OR = 0.78; 95% CI: 0.62–0.98), comatose LOC (OR = 0.36;95%CI: 0.27–0.48; ref. = alert), pre-stroke dependency (OR = 0.72; 95% CI: 0.58–0.91), and NOAC treatment (OR = 0.34; 95% CI: 0.28–0.42). Care at a university hospital was not associated with higher odds of receiving reversal treatment compared to treatment at a county hospital. Conclusion: Treatment with a reversal agent following OAC-ICH was related to several patient factors including type of OAC drug. We identified that only 48% of patients with NOAC-ICH received hemostatic treatment despite an increase in these cases. Further studies are required to guide the use of reversal therapies more precisely, particularly in NOAC-ICH.
35.	Apostolaki-Hansson, Trine, et al. (författare) Prognosis for intracerebral hemorrhage during ongoing oral anticoagulant treatment 2019 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 139:5, s. 415-421 Tidskriftsartikel (refereegranskat)abstract Background: Intracerebral hemorrhage (ICH) is the most serious adverse effect of treatment with oral anticoagulants. Prognostic data after ICH associated with non-vitamin K antagonist oral anticoagulants (NOAC) compared to vitamin K antagonists (VKA) are sparse. We compared 90-day survival and functional outcome following NOAC-ICH versus VKA-ICH using data from the Swedish Stroke Register (Riksstroke). Methods: Using data from Riksstroke and the Swedish Causes of Death Register between 2012 and 2016, we compared all-cause 90-day mortality for patients with NOAC-ICH versus VKA-ICH using Kaplan-Meier survival analysis and Log-rank test. Cox regression, with adjustment for age, sex, previous stroke, and level of consciousness (LOC) on admission, was used to estimate hazard ratios (HR) for 90-day mortality. Estimated functional outcome at 90 days, based on the modified Rankin Scale (mRS), was compared between VKA- and NOAC-associated ICH using chi-squared test. Results: We included 2483 patients; 300 with NOAC-ICH and 2183 with VKA-ICH. In both groups, mean age was 79 years, and 58% were male. No significant difference between NOAC-ICH and VKA-ICH was found for all-cause 90-day mortality (44.3% NOAC-ICH versus 42.6% VKA-ICH; P = 0.54, HR = 0.93; 95% confidence interval (CI): 0.78-1.12) or 90-day estimated functional outcome (mRS 0-2:13.7% and 15.3%; mRS 3-5:27.3% and 28.9%, respectively (P = 0.52)). Factors predicting death were increased age (HR = 1.03; 95%CI: 1.02-1.04) and reduced LOC (drowsy: HR = 3.48; 95%CI: 2.86-4.23; comatose: HR = 12.27; 95%CI: 10.13-14.87). Conclusion: In this large study on anticoagulant-associated ICH, we found no significant difference in mortality and functional outcome at 90 days between NOAC-ICH versus VKA-ICH.
36.	Apostolaki-Hansson, Trine, et al. (författare) Prognosis of Intracerebral Hemorrhage Related to Antithrombotic Use : An Observational Study From the Swedish Stroke Register (Riksstroke) 2021 Ingår i: Stroke. - 1524-4628. ; 52:3, s. 966-974 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND PURPOSE: To date, large studies comparing mortality and functional outcome of intracerebral hemorrhage (ICH) during oral anticoagulant (OAC), antiplatelet, and nonantithrombotic use are few and show discrepant results. METHODS: We used data on 13 291 patients with ICH registered in Riksstroke between 2012 and 2016 to compare 90-day mortality and functional outcome following OAC-related ICH (n=2300), antiplatelet-related ICH (n=3637), and nonantithrombotic ICH (n=7354). Univariable and multivariable Cox regression analyses, with adjustment for relevant confounders, were used to compare 90-day mortality. Early (≤24 hours and 1-7 days) and late (8-90 days) mortality was also studied in subgroup analyses. Univariable and multivariable 90-day functional outcome, based on self-reported modified Rankin Scale, was determined using logistic regression. RESULTS: Patients with antithrombotic treatment were more often prestroke dependent, older, and had a larger comorbidity burden compared with patients without antithrombotic treatment. At 90 days, antiplatelet and OAC were associated with an increased death rate in multivariable analysis (antiplatelet ICH: hazard ratio, 1.23 [95% CI, 1.14-1.33]; OAC ICH: hazard ratio, 1.40 [95% CI, 1.26-1.57]) compared with nonantithrombotic ICH (reference). OAC ICH and antiplatelet ICH were associated with higher risk of early mortality (≤24 hours: OAC ICH: hazard ratio, 1.93 [95% CI, 1.57-2.38]; antiplatelet ICH: hazard ratio, 1.32 [95% CI, 1.13-1.54]). In multivariable analysis, the odds ratios for the association of antiplatelet and OAC treatment on functional dependency (modified Rankin Scale score, 3-5) at 90 days were nonsignificant (antiplatelet: odds ratio, 1.07 [95% CI, 0.92-1.24]; OAC: odds ratio, 0.96 [95% CI, 0.76-1.22]). CONCLUSIONS: In this large observational study, we found that 90-day mortality outcome was worse not only in OAC ICH but also in antiplatelet ICH, compared with patients with nonantithrombotic ICH. Antiplatelet ICH is common and is a serious condition with poor clinical outcome. Further studies are, therefore, warranted in determining the appropriate clinical management of these patients.
37.	Apostolaki-Hansson, Trine, et al. (författare) Reversal Treatment in Oral Anticoagulant-Related Intracerebral Hemorrhage—An Observational Study Based on the Swedish Stroke Register 2020 Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11 Tidskriftsartikel (refereegranskat)abstract Introduction: Intracerebral hemorrhage (ICH) is the most serious adverse effect of oral anticoagulant (OAC) treatment. The effect of OAC reversal therapy on outcome is uncertain. We compared 90-day survival and functional outcome in patients with OAC-ICH who received OAC reversal therapy with those who did not. Methods: Data from The Swedish Stroke Register (Riksstroke) for all registered cases of OAC-ICH during 2017 (572 patients) were used to obtain information on reversal (n = 369) and non-reversal (n = 203) treatment receiving patients. Univariate and multivariate Cox regression analysis stratified for level of consciousness (LOC) on admission, and adjustment for relevant baseline variables, was used to compare 90-day Hazard Ratios (HR) for mortality. Results: Sixty-five percent of patients received reversal treatment. These patients were younger, more often pre-stroke independent and alert at presentation. Withholding reversal treatment was associated with an increased death rate (HR = 1.47; 95% CI: 1.08–2.01) in a Cox regression model stratified for LOC and adjusted for baseline imbalances. Additional factors associated with an increased 90-day death rate were male sex (HR = 1.42; 95% CI: 1.06–1.92), age (HR = 1.05; 95% CI: 1.02–1.07), and intraventricular hemorrhage (HR = 2.41; CI: 1.77–3.29). Conclusion: In this large observational study 35% of patients with OAC-ICH did not receive reversal treatment. Patients receiving OAC-reversal treatment had an improved 90-day mortality outcome compared to those not receiving treatment. Mortality was strongly related to LOC. Further, and larger, studies are required to determine which patient groups may benefit from reversal therapy and in whom non-reversal is adequate.
38.	Appelros, Peter, et al. (författare) Trends in baseline patient characteristics during the years 1995-2008 : observations from Riks-Stroke, the Swedish Stroke Register. 2010 Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 30:2, s. 114-119 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Reported improvements in outcome in stroke patients treated in hospital are often attributed to advances in stroke care. However, secular trends in patient characteristics that are present already on admission to hospital may also contribute to improved outcome. METHODS: Time trends for baseline data (289,854 stroke admittances) in Riks-Stroke, the Swedish national quality register for stroke care, were analyzed for the years 1995 through 2008. The following data were included: number of strokes for each year, age, sex, risk factors, stroke subtype, stroke severity, functional status and need of external home service before the stroke. RESULTS: The number of annually reported strokes increased until 2005. The proportion of recurrent strokes decreased from 28.0 to 25.9%. The mean age at first-ever stroke increased in women, but not in men. The proportion of smokers dropped, and the proportion of patients who had treated hypertension increased. The stroke severity decreased in men. The prestroke functional status (walking, dressing, toileting) improved in both sexes over these years. More patients lived alone in 2008 than in 1995, and more had home help service. CONCLUSIONS: Many baseline parameters in Riks-Stroke have changed over the years. This has consequences for the interpretation of outcome data. Some changes may be due to inclusion bias, others due to alterations in general health, evolution of vascular risk factors or demographics.
39.	Appelros, Peter, 1953-, et al. (författare) Trends in Stroke Treatment and Outcome between 1995 and 2010 : Observations from Riks-Stroke, the Swedish Stroke Register 2014 Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 37:1, s. 22-29 Tidskriftsartikel (refereegranskat)abstract Background: Continuous changes in stroke treatment and care, as well as changes in stroke characteristics, may alter stroke outcome over time. The aim of this paper is to describe time trends for treatment and outcome data, and to discuss if any such changes could be attributed to quality changes in stroke care. Methods: Data from Riks-Stroke, the Swedish stroke register, were analyzed for the time period of 1995 through 2010. The total number of patients included was 320,181. The following parameters were included: use of computed tomography (CT), stroke unit care, thrombolysis, medication before and after the stroke, length of stay in hospital, and discharge destination. Three months after stroke, data regarding walking, toileting and dressing ability, as well social situation, were gathered. Survival status after 7, 27 and 90 days was registered. Results: In 1995, 53.9% of stroke patients were treated in stroke units. In 2010 this proportion had increased to 87.5%. Fewer patients were discharged to geriatric or rehabilitation departments in later years (23.6% in 2001 compared with 13.4% in 2010), but more were discharged directly home (44.2 vs. 52.4%) or home with home rehabilitation (0 vs. 10.7%). The need for home help service increased from 18.2% in 1995 to 22.1% in 2010. Regarding prevention, more patients were on warfarin, antihypertensives and statins both before and after the stroke. The functional outcome measures after 3 months did improve from 2001 to 2010. In 2001, 83.8% of patients were walking independently, while 85.6% were independent in 2010. For toileting, independence increased from 81.2 to 84.1%, and for dressing from 78.0 to 80.4%. Case fatality (CF) rates after 3 months increased from 18.7% (2001) to 20.0% (2010). This trend is driven by patients with severe strokes. Conclusions: Stroke outcomes may change over a relatively short time period. In some ways, the quality of care has improved. More stroke patients have CT, more patients are treated in stroke units and more have secondary prevention. Patients with milder strokes may have benefited more from these measures than patients with severe strokes. Increased CF rates for patients with severe stroke may be caused by shorter hospital stays, shorter in-hospital rehabilitation periods and lack of suitable care after discharge from hospital.
40.	Asplund, Kjell, et al. (författare) Effects of Extending the Time Window of Thrombolysis to 4.5 Hours : Observations in the Swedish Stroke Register (Riks-Stroke) 2011 Ingår i: Stroke. - New York : American Heart Association. - 0039-2499 .- 1524-4628. ; 42:9, s. 2492-2497 Tidskriftsartikel (refereegranskat)abstract Background and Purpose: The European Cooperative Acute Stroke Study (ECASS) III trial and Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register (SITS-ISTR) data were published in 2008. Riks-Stroke, the Swedish Stroke Register, was used to explore how thrombolysis in the 3- to 4.5-hour window has been spread in different hospitals and patient groups and what effects this has had on treatment within 3 hours.Methods: All 76 hospitals in Sweden admitting patients with acute stroke participate in Riks-Stroke. During the study period, January 2003 to June 2010, 92 150 18- to 80-year-old patients were hospitalized for acute ischemic stroke.Results: After the publication of the ECASS III results in the third quarter of 2008, thrombolysis in the 3- to 4.5-hour window increased from 0.5% before publication to 2.1% in 2010. Thrombolysis in the 3- to 4.5-hour window spread somewhat faster in men than women (P=0.04) but at a similar rate in different age groups. The use of thrombolysis within 3 hours after onset of symptoms increased successively from 0.9% in 2003 to 6.6% in late 2008 and then it stabilized at 6%. The median time from arrival to the hospital to start of treatment remained unchanged at 66 to 69 minutes before and after 2008 (P=0.06).Conclusions: Since the end of 2008, there has been a rapid nationwide dissemination of thrombolysis in the 3- to 4.5-hour window, whereas rates in the <3-hour window have leveled off. The extended time window has not affected door-to-needle time.
41.	Asplund, Kjell, et al. (författare) Hemikraniektomi är livräddande, visar Riks-Stroke : erfarenheter av ingreppet vid malign hjärninfarkt och intracerebral blödning 2014 Ingår i: Läkartidningen. - : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 111:3-4 Tidskriftsartikel (refereegranskat)abstract From 2009 to mid-2013, 229 hemicraniectomies were reported in Riks-Stroke, of which 43 were performed in patients with intracerebral hemorrhage. In patients with brain infarction, it was performed in 0.19% (all ages) and 1.07% (below 60 years), higher than reported from the US. Of the hemicraniectomies, 45% were performed in patients above 60 years. Survival was 83% at 3 months and 81% at 12 months, similar to survival reported in the literature. Three months after hemicraniectomy, 69% of survivors responded to a follow-up questionnaire. Of these, 31% were independent in personal ADL and 46% were living at home. Case fatality was higher but functional outcome in survivors was similar in patients above 60 years compared to below 60. In conclusion, outcomes are similar in Sweden to those reported in randomized trials and international observational studies. With proper patient selection, it seems that hemicraniectomy may also benefit patients above 60 years.
42.	Asplund, Kjell, et al. (författare) Patient dissatisfaction with acute stroke care 2009 Ingår i: Stroke. - : American Heart Association, Inc.. - 0039-2499 .- 1524-4628. ; 40:12, s. 3851-3856 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND PURPOSE: Riks-Stroke, the Swedish Stroke Register, was used to explore patient characteristics and stroke services as determinants of patient dissatisfaction with acute in-hospital care. METHODS: All 79 hospitals in Sweden admitting acute stroke patients participate in Riks-Stroke. During 2001 to 2007, 104,876 patients (87% of survivors) responded to a follow-up questionnaire 3 months after acute stroke; this included questions on satisfaction with various aspects of stroke care. RESULTS: The majority (>90%) were satisfied with acute in-hospital stroke care. Dissatisfaction was closely associated with outcome at 3 months. Patient who were dependent regarding activities of daily living, felt depressed, or had poor self-perceived general health were more likely to be dissatisfied. Dissatisfaction with global acute stroke care was linked to dissatisfaction with other aspects of care, including rehabilitation and support by community services. Patients treated in stroke units were less often dissatisfied than patients in general wards, as were patients who had been treated in a small hospital (vs medium or large hospitals) and patient who had participated in discharge planning. In multivariate analyses, the strongest predictor of dissatisfaction with acute care was poor outcome (dependency regarding activities of daily living, depressed mood, poor self-perceived health). CONCLUSIONS: Dissatisfaction with in-hospital acute stroke care is part of a more extensive complex comprising poor functional outcome, depressive mood, poor self-perceived general health, and dissatisfaction not only with acute care but also with health care and social services at large. Several aspects of stroke care organization are associated with a lower risk of dissatisfaction.
43.	Asplund, Kjell, et al. (författare) Riks-stroke - a Swedish national quality register for stroke care. 2003 Ingår i: Cerebrovasc Dis. - 1015-9770. ; 15 Suppl 1, s. 5-7 Tidskriftsartikel (refereegranskat)
44.	Asplund, Kjell, et al. (författare) The Riks-Stroke story : building a sustainable national register for quality assessment of stroke care 2011 Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 6:2, s. 99-108 Tidskriftsartikel (refereegranskat)abstract Background Riks-Stroke, the Swedish Stroke Register, is the world's longest-running national stroke quality register (established in 1994) and includes all 76 hospitals in Sweden admitting acute stroke patients. The development and maintenance of this sustainable national register is described. Methods Riks-Stroke includes information on the quality of care during the acute phase, rehabilitation and secondary prevention of stroke, as well as data on community support. Riks-Stroke is unique among stroke quality registers in that patients are followed during the first year after stroke. The data collected describe processes, and medical and patient-reported outcome measurements. The register embraces most of the dimensions of health-care quality (evidence-based, safe, provided in time, distributed fairly and patient oriented). Result Annually, approximately 25 000 patients are included. In 2009, approximately 320 000 patients had been accumulated (mean age 76-years). The register is estimated to cover 82% of all stroke patients treated in Swedish hospitals. Among critical issues when building a national stroke quality register, the delicate balance between simplicity and comprehensiveness is emphasised. Future developments include direct transfer of data from digital medical records to Riks-Stroke and comprehensive strategies to use the information collected to rapidly implement new evidence-based techniques and to eliminate outdated methods in stroke care. Conclusions It is possible to establish a sustainable quality register for stroke at the national level covering all hospitals admitting acute stroke patients. Riks-Stroke is fulfilling its main goals to support continuous quality improvement of Swedish stroke services and serve as an instrument for following up national stroke guidelines.
45.	Ay, Hakan, et al. (författare) International Validation of a Computerized Algorithm for Etiologic Classification of Ischemic Stroke: The Causative Classification of Stroke System 2009 Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 40:4, s. 203-203 Konferensbidrag (refereegranskat)
46.	Ay, Hakan, et al. (författare) Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network 2014 Ingår i: Stroke. - 0039-2499. ; 45:12, s. 3589-3596 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.
47.	Beharry, James, et al. (författare) Recurrent ischemic stroke and mortality in stroke patients without standard modifiable risk factors : an analysis of the riksstroke registry Annan publikation (övrigt vetenskapligt/konstnärligt)
48.	Bellenguez, Celine, et al. (författare) Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke 2012 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:3, s. 141-328 Tidskriftsartikel (refereegranskat)abstract Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
49.	Bergqvist, D, et al. (författare) Haverikommission granskade karotiskirurgins komplikationer. Hälften kunde förklaras med misstag eller tveksamma indikationer 2000 Ingår i: Läkartidningen. - 0023-7205. ; 97:14, s. 1673-1676 Tidskriftsartikel (refereegranskat)abstract As carotid endarterectomy is a prophylactic procedure, it would seem particularly important to analyze complications with an aim to avoiding them. All carotid endarterectomies in Sweden are registered, and all serious complications (death and permanent neurological deficit) are analyzed in detail, classified and discussed within the profession. During the period 1994-1996 the frequency was 4.3 percent (technical causes in 17 percent, contraindications in 8 percent and dubious indications in 21 percent, but correct indication and surgery in 54 percent). Thus, even when conditions are optimal there is a certain price to pay for the prevention of ischemic stroke.
50.	Best, Jonathan G., et al. (författare) Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) : Protocol for a randomized controlled trial 2022 Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 17:5, s. 583-589 Tidskriftsartikel (refereegranskat)abstract Rationale: Atrial fibrillation causes one-fifth of ischemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke is usually delayed by concerns over intracranial hemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial hemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of recurrence, but the safety and efficacy of this approach has not been established. Aim: Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) will investigate whether early treatment with a direct oral anticoagulant, within four days of stroke onset, is as effective or better than delayed initiation, 7 to 14 days from onset, in atrial fibrillation patients with acute ischemic stroke. Methods and design: OPTIMAS is a multicenter randomized controlled trial with blinded outcome adjudication. Participants with acute ischemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomized 1:1 to early or delayed initiation. As of December 2021, 88 centers in the United Kingdom have opened. Study outcomes: The primary outcome is a composite of recurrent stroke (ischemic stroke or symptomatic intracranial hemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include major bleeding, functional status, anticoagulant adherence, quality of life, health and social care resource use, and length of hospital stay. Sample size target: A total of 3478 participants assuming event rates of 11.5% in the control arm and 8% in the intervention arm, 90% power and 5% alpha. We will follow a non-inferiority gatekeeper analysis approach with a non-inferiority margin of 2 percentage points. Discussion: OPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated ischemic stroke. Trial registrations: ISRCTN: 17896007; ClinicalTrials.gov: NCT03759938

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