Publications by authors named "Bo Norrving"

270 Publications

Effects of Fluoxetine on Outcomes at 12 Months After Acute Stroke: Results From EFFECTS, a Randomized Controlled Trial.

Stroke 2021 Oct 31;52(10):3082-3087. Epub 2021 Aug 31.

Institute of Neuroscience and Physiology-Clinical Neuroscience, The Sahlgrenska Academy, University of Gothenburg, Sweden (K.S.S.).

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.121.034705DOI Listing
October 2021

Editorial.

Eur Stroke J 2021 Jun 18;6(2):109-110. Epub 2021 Jun 18.

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http://dx.doi.org/10.1177/23969873211025831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370084PMC
June 2021

The state of stroke services across the globe: Report of World Stroke Organization-World Health Organization surveys.

Int J Stroke 2021 May 27:17474930211019568. Epub 2021 May 27.

National Institute for Stroke and Applied Neurosciences (NISAN), School of Clinical Sciences, Auckland University of Technology, New Zealand.

Background: Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization-World Health Organization- Commission on Stroke conducted a survey of the status of stroke services in low and middle-income countries (LMICs) compared to high-income countries.

Methods: Using a validated World Stroke Organization comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across World Health Organization regions and economic strata. The World Health Organization also conducted a survey of non-communicable diseases in 194 countries in 2019.

Results: Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys, and participation in research) were reported in low-income countries than high-income countries. The overall global score for prevention was 40.2%. Stroke units were present in 91% of high-income countries in contrast to 18% of low-income countries (p < 0.001). Acute stroke treatments were offered in ∼ 60% of high-income countries compared to 26% of low-income countries (p = 0.009). Compared to high-income countries, LMICs provided less rehabilitation services including in-patient rehabilitation, home assessment, community rehabilitation, education, early hospital discharge program, and presence of rehabilitation protocol.

Conclusions: There is an urgent need to improve access to stroke units and services globally especially in LMICs. Countries with less stroke services can adapt strategies from those with better services. This could include establishment of a framework for regular monitoring of stroke burden and services, implementation of integrated prevention activities and essential acute stroke care services, and provision of interdisciplinary care for stroke rehabilitation.
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http://dx.doi.org/10.1177/17474930211019568DOI Listing
May 2021

Late stroke after transcatheter aortic valve replacement: a nationwide study.

Sci Rep 2021 05 5;11(1):9593. Epub 2021 May 5.

Department of Cardiothoracic Surgery, Skåne University Hospital, Lund University, 221 85, Lund, Sweden.

Transcatheter aortic valve replacement (TAVR) is a rapidly growing field. Short-term safety and efficacy of these procedures have been studied extensively. However, little is known about the safety of these devices over time. Stroke is one feared long-term complication, and an increased stroke rate could affect guidelines for treating both the aortic stenosis and choosing antithrombotic therapy after TAVR. The primary objective was to study the incidence of stroke up to 8 years after TAVR implantation, comparing it with the risk of stroke in the general population. Secondary objectives were to study risk factors for late stroke and to study outcomes after stroke. A nationwide, all-comers study of patients who underwent TAVR in Sweden 2008-2018 was performed. The study was based on data from three national registries: a TAVR registry, a stroke registry, and a diagnosis registry. The main outcome was stroke incidence 30-days or more after TAVR implantation and was compared to a standardized incidence. The annual risk for stroke varied between 2.0% and 3.1% as compared to 1.5% and 1.9% in an age- and sex-matched cohort. Risk factors for developing stroke were reduced renal function, diabetes, history of stroke, age, and male sex. The 1-year mortality after stroke was 44%. This study demonstrated an increased rate of stroke after TAVR, but the findings suggest that this can in part be attributed to the group's higher frequency of pre-disposing risk factors.
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http://dx.doi.org/10.1038/s41598-021-89217-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100158PMC
May 2021

Mortality After Ischemic Stroke in Patients with Alzheimer's Disease Dementia and Other Dementia Disorders.

J Alzheimers Dis 2021 ;81(3):1253-1261

Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

Background: Stroke and dementia are interrelated diseases and risk for both increases with age. Even though stroke incidence and age-standardized death rates have decreased due to prevention of stroke risk factors, increased utilization of reperfusion therapies, and other changes in healthcare, the absolute numbers are increasing due to population growth and aging.

Objective: To analyze predictors of death after stroke in patients with dementia and investigate possible time and treatment trends.

Methods: A national longitudinal cohort study 2007-2017 using Swedish national registries. We compared 12,629 ischemic stroke events in patients with dementia with matched 57,954 stroke events in non-dementia controls in different aspects of patient care and mortality. Relationship between dementia status and dementia type (Alzheimer's disease and mixed dementia, vascular dementia, other dementias) and death was analyzed using Cox regressions.

Results: Differences in receiving intravenous thrombolysis between patients with and without dementia disappeared after the year 2015 (administered to 11.1% dementia versus 12.3% non-dementia patients, p = 0.117). One year after stroke, nearly 50% dementia and 30% non-dementia patients had died. After adjustment for demographics, mobility, nursing home placement, and comorbidity index, dementia was an independent predictor of death compared with non-dementia patients (HR 1.26 [1.23-1.29]).

Conclusion: Dementia before ischemic stroke is an independent predictor of death. Over time, early and delayed mortality in patients with dementia remained increased, regardless of dementia type. Patients with≤80 years with prior Alzheimer's disease or mixed dementia had higher mortality rates after stroke compared to patients with prior vascular dementia.
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http://dx.doi.org/10.3233/JAD-201459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293632PMC
September 2021

Falls After Stroke: A Follow-up after Ten Years in Lund Stroke Register.

J Stroke Cerebrovasc Dis 2021 Jun 8;30(6):105770. Epub 2021 Apr 8.

Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden; Section of Neurology, Skåne University Hospital, Lund, Sweden. Electronic address:

Objectives: To evaluate incidence of self-reported falls and associated factors in a ten-year perspective after stroke.

Methods: From a population-based cohort of first-ever stroke patients (n = 416) included in the Lund Stroke Register between March 1, 2001, and February 28, 2002, we performed a follow up of all 145 survivors ten years after stroke. We collected data on age, gender, main stroke type, living and housing situation, general health status (question 1 in the Short Form Health Survey (SF-36), dizziness, physical activity, Barthel Index, mobility aids, moving ability inside/outside, and health-related quality of life as defined by the EuroQol 3 dimension scale (EQ-5D-3L). Factors that may relate to falls were compared between those who had experienced falls after stroke or not.

Results: Ten years after stroke, 49 patients (34 %) reported falls and 96 patients (66 %) reported no falls. Compared to patients with no falls, those who reported falls were older (median age 83.3 years vs 75.6 years; p < 0.001), more often lived alone, were more dependent in daily living, had less physical activity, poorer general health status, more often needed mobility aids, were more often unable to move alone outside, and had poorer health-related quality of life in all items in EQ-5D-3L except pain/discomfort.

Conclusions: Falls had occurred in approximately one third of the participants ten years after the stroke, and were strongly associated with several measures of frailty. Our results indicate that fall prevention should in particular focus on those at high risk of falls.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105770DOI Listing
June 2021

Editorial.

Eur Stroke J 2021 Mar 22;6(1):3-4. Epub 2021 Mar 22.

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http://dx.doi.org/10.1177/23969873211004043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995318PMC
March 2021

Editorial.

Eur Stroke J 2020 Dec 8;5(4):327. Epub 2020 Dec 8.

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http://dx.doi.org/10.1177/2396987320981194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856582PMC
December 2020

Prognosis of Intracerebral Hemorrhage Related to Antithrombotic Use: An Observational Study From the Swedish Stroke Register (Riksstroke).

Stroke 2021 Mar 10;52(3):966-974. Epub 2021 Feb 10.

Department of Neurology, Lund University, Skåne University Hospital, Sweden (T.A.-H., T.U., B.N., J.P.).

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.
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http://dx.doi.org/10.1161/STROKEAHA.120.030930DOI Listing
March 2021

Imaging Markers of Brain Frailty and Outcome in Patients With Acute Ischemic Stroke.

Stroke 2021 Mar 28;52(3):1004-1011. Epub 2021 Jan 28.

Stroke Division (V.T.), The Florey Institute of Neuroscience and Mental Health.

Background And Purpose: Functional outcome after stroke may be related to preexisting brain health. Several imaging markers of brain frailty have been described including brain atrophy and markers of small vessel disease. We investigated the association of these imaging markers with functional outcome after acute ischemic stroke.

Methods: We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial (AX200 in Ischemic Stroke Trial), a randomized controlled clinical trial of granulocyte colony-stimulating factor versus placebo. We assessed the ratio of brain parenchymal volume to total intracerebral volumes (ie, the brain parenchymal fraction) and total brain volumes from routine baseline magnetic resonance imaging data obtained within 9 hours of symptom onset using the unified segmentation algorithm in SPM12. Enlarged perivascular spaces, white matter hyperintensities, lacunes, as well as a small vessel disease burden, were rated visually. Functional outcomes (modified Rankin Scale score) at day 90 were determined. Logistic regression was used to test associations between brain imaging features and functional outcomes.

Results: We enrolled 259 patients with a mean age of 69±12 years and 46 % were female. Increased brain parenchymal fraction was associated with higher odds of excellent outcome (odds ratio per percent increase, 1.078 [95% CI, 1.008-1.153]). Total brain volumes and small vessel disease burden were not associated with functional outcome. An interaction between brain parenchymal fraction and large vessel occlusion on excellent outcome was not observed.

Conclusions: Global brain health, as assessed by brain parenchymal fraction on magnetic resonance imaging, is associated with excellent functional outcome after ischemic stroke. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00927836.
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http://dx.doi.org/10.1161/STROKEAHA.120.029841DOI Listing
March 2021

Burden of Neurological Disorders Across the US From 1990-2017: A Global Burden of Disease Study.

JAMA Neurol 2021 Feb;78(2):165-176

Department of Systems, Populations, and Leadership, University of Michigan, Ann Arbor.

Importance: Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US.

Objective: To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017.

Design, Setting, And Participants: This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.

Exposures: Any of the 14 listed neurological diseases.

Main Outcome And Measure: Absolute numbers in detail by age and sex and age-standardized rates (with 95% uncertainty intervals) were calculated.

Results: The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (-29.1% [95% UI, -32.4% to -25.8%]); spinal cord injury prevalence (-38.5% [95% UI, -43.1% to -34.0%]); meningitis prevalence (-44.8% [95% UI, -47.3% to -42.3%]), deaths (-64.4% [95% UI, -67.7% to -50.3%]), and DALYs (-66.9% [95% UI, -70.1% to -55.9%]); and encephalitis DALYs (-25.8% [95% UI, -30.7% to -5.8%]). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus.

Conclusions And Relevance: There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders.
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http://dx.doi.org/10.1001/jamaneurol.2020.4152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607495PMC
February 2021

Patterns in hospital readmissions after ischaemic stroke - An observational study from the Swedish stroke register (Riksstroke).

Eur Stroke J 2020 Sep 15;5(3):286-296. Epub 2020 Jun 15.

Stroke Policy and Quality Register Research Group, Lund university, Sweden.

Introduction: While acute treatment and secondary prevention in stroke have undergone major improvements, hospital readmission after index stroke remains high. However, there are few reports on long-term readmission patterns.

Patients And Methods: For this prospective observational study, data on demographics, functional status and living conditions were obtained from the Swedish Stroke Register (Riksstroke). Data on comorbidity and hospital readmissions up to five years post-index stroke were obtained from the Swedish National Patient Register. Patients were grouped based on number of readmissions: low (0-1) intermediate (2-4), high (5-9) or very high (≥10).

Results: Of the 10,092 patients included, 43.7% had been readmitted within 12 months and 74.0% within 5 years. There was an average of three readmissions per individual during the five-year interval. A small group of patients with a high-comorbidity burden accounted for the majority of readmissions: approximately 20% of patients accounted for 60% of readmissions, and 5% of patients accounted for 25%. Circulatory conditions were the most common cause followed by infectious disease, stroke, trauma and diseases of the nervous system other than stroke. The proportion of readmissions due to stroke decreased sharply in the first six months.

Conclusion: A small number of patients with a high degree of comorbidity accounted for the majority of hospital readmissions after index stroke. Our results highlight the need for further development of strategies to support high-risk comorbid stroke patients in the community setting. Further research describing characteristics and healthcare utilisation patterns in this group is warranted.
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http://dx.doi.org/10.1177/2396987320925205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538769PMC
September 2020

Editorial.

Eur Stroke J 2020 Sep 1;5(3):217-218. Epub 2020 Oct 1.

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http://dx.doi.org/10.1177/2396987320953932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538758PMC
September 2020

Reversal Treatment in Oral Anticoagulant-Related Intracerebral Hemorrhage-An Observational Study Based on the Swedish Stroke Register.

Front Neurol 2020 29;11:760. Epub 2020 Jul 29.

"Stroke Policy and Quality Register Research" Group, Department of Neurology, Skåne University Hospital, Lund University, Lund, Sweden.

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. 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 ( = 369) and non-reversal ( = 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. 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 ( = 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 ( = 1.42; 95% CI: 1.06-1.92), age ( = 1.05; 95% CI: 1.02-1.07), and intraventricular hemorrhage ( = 2.41; CI: 1.77-3.29). 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.
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http://dx.doi.org/10.3389/fneur.2020.00760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438936PMC
July 2020

Differences in self-perceived general health, pain, and depression 1 to 5 years post-stroke related to work status at 1 year.

Sci Rep 2020 08 6;10(1):13251. Epub 2020 Aug 6.

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, and Sahlgrenska University Hospital, Gothenburg, Sweden.

Stroke is one of the most common diseases and has several potential consequences, such as psychological problems and pain. Return to work (RTW) after stroke in working-age individuals is incomplete. The present study aimed to investigate differences in self-perceived general health, pain, and depression between 1 and 5 years post-stroke related to RTW status. The study was nationwide, registry-based and the study population (n = 398) consisted of working-age people who had a stroke in 2011 and participated in 1-year and 5-year follow-up questionnaire surveys. Shift analyses with the Wilcoxon signed rank test and logistic regression were used. RTW within the first year post-stroke was associated with better self-perceived general health, less pain, and less depression both at 1 and 5 years post-stroke, compared with the no-RTW group. However, the RTW group had significant deterioration in general health and pain between 1 and 5 years, while the no-RTW group had no significant change. RTW was a significant predictor of lower odds of improvement in general health and pain between 1 and 5 years. This emphasizes the need for continued follow-up and support to ensure a balance between work and health for RTW individuals after stroke.
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http://dx.doi.org/10.1038/s41598-020-70228-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413535PMC
August 2020

Ischemic stroke patients with prestroke dependency: Characteristics and long-term prognosis.

Acta Neurol Scand 2021 Jan 18;143(1):78-88. Epub 2020 Aug 18.

Stroke Policy and Quality Register Research Group, Lund University, Lund, Sweden.

Objective: This paper aims at examining the clinical characteristics of ischemic stroke patients with different levels of prestroke functional dependency, their long-term outcome, and determinants of five-year mortality.

Materials And Methods: We describe demographics, comorbidity, treatment, as well as long-term mortality, and functional status of 5899 prestroke-dependent ischemic stroke patients stratified by dependency level and compared to a concurrent cohort of 14 148 prestroke-independent patients. The study was based on 2016 survey data from Riksstroke, the Swedish national stroke register, and patients were followed up at three months, 12 months, and either at three or five years. We used Cox regression for mortality predictor analysis and multiple imputation was performed to minimize bias from loss to follow-up.

Results: With increasing level of prestroke dependency, comorbidity burden was higher, drug prescription lower, and prognosis less favorable. At three years, the proportion that had died or deteriorated were 82.6%, 87.5%, and 86.3% in moderate, moderately severe, and severe dependency, respectively. In moderate dependency, prognosis was relatively favorable: Three-month mortality was half of that seen in severe dependency (25.3% versus 49.6%). Differences in overall outcome between groups of varying prestroke functional dependency level were statistically significant (P < .05) at all follow-up time points.

Conclusions: There was great heterogeneity between groups of different level of prestroke dependency; those of moderate dependency had a relatively favorable prognosis. Patients of different prestroke level of dependency need to be addressed separately, and further research is needed characterizing this group and exploring management strategies.
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http://dx.doi.org/10.1111/ane.13328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754457PMC
January 2021

Editorial.

Eur Stroke J 2020 Jun 21;5(2):111-112. Epub 2020 Jun 21.

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http://dx.doi.org/10.1177/2396987320922322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313368PMC
June 2020

In-Hospital Delays in Stroke Thrombolysis: Every Minute Counts.

Stroke 2020 08 26;51(8):2536-2539. Epub 2020 Jun 26.

Department of Statistics, Umeå School of Business, Economics and Statistics (M.E.), Umeå University, Sweden.

Background And Purpose: Intravenous thrombolysis is a well-established treatment for acute ischemic stroke. Our aim was to quantify the effect of each minute delay in door-to-needle time (DNT) on 90-day survival, intracerebral hemorrhagic complication <36 hours, and functional outcomes at 3 months, in routine clinical practice.

Methods: Our nationwide registry-based study included 14 132 adult patient admissions with ischemic stroke receiving intravenous thrombolysis from 2010 to 2017. Outcomes were analyzed using multivariable logistic regression, adjusting for potential confounders.

Results: Median DNT was 47 minutes, with an improvement from 65 to 38 minutes during the study. Median age was 74 years, and median National Institutes of Health Stroke Scale 8 points. We found a significant impact of each minute delay in DNT with reduced odds of survival by 0.6%, increased odds of intracerebral hemorrhagic and worse activities of daily living by 0.3%, and worse living conditions and mobility by 0.4%.

Conclusions: Improving DNT is a key factor in achieving good outcomes after stroke. We estimate that in Sweden alone in 2017, compared with 2010, the shorter DNT achieved have saved 38 lives, avoided 8 intracerebral hemorrhagic transformations, and spared, respectively, 36, 51, and 52 patients from a worsening in activities of daily living, living conditions, and mobility. DNT is sensitive for interventions and should be targeted in quality improvement efforts.
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http://dx.doi.org/10.1161/STROKEAHA.120.029468DOI Listing
August 2020

Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis.

J Neurol 2020 Oct 9;267(10):3021-3037. Epub 2020 Jun 9.

Department of Neurology, The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland.

Background: The prevalence of ex vivo 'high on-treatment platelet reactivity (HTPR)' and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear.

Methods: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes. Data were pooled using random-effects meta-analysis. Primary outcome was the composite risk of recurrent stroke/TIA, myocardial infarction or vascular death. Secondary outcomes were recurrent stroke/TIA, severe stroke (NIHSS > 16) or disability/impairment (modified Rankin scale ≥ 3) during follow-up.

Results: Antiplatelet-HTPR prevalence was 3-65% with aspirin, 8-56% with clopidogrel and 1.8-35% with aspirin-clopidogrel therapy. Twenty studies (4989 patients) were included in our meta-analysis. There was a higher risk of the composite primary outcome (OR 2.93, 95% CI 1.90-4.51) and recurrent ischaemic stroke/TIA (OR 2.43, 95% CI 1.51-3.91) in patients with vs. those without 'antiplatelet-HTPR' on any antiplatelet regimen. These risks were also more than twofold higher in patients with vs. those without 'aspirin-HTPR' and 'dual antiplatelet-HTPR', respectively. Clopidogrel-HTPR status did not significantly predict outcomes, but the number of eligible studies was small. The risk of severe stroke was higher in those with vs. without antiplatelet-HTPR (OR 2.65, 95% CI 1.00-7.01).

Discussion: Antiplatelet-HTPR may predict risks of recurrent vascular events/outcomes in CVD patients. Given the heterogeneity between studies, further prospective, multi-centre studies are warranted.
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http://dx.doi.org/10.1007/s00415-020-09932-yDOI Listing
October 2020

Correction to: Update on the EFFECTS study of fluoxetine for stroke recovery: a randomised controlled trial in Sweden.

Trials 2020 05 7;21(1):388. Epub 2020 May 7.

Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Following publication of the original article [1], we were notified that one of the corresponding author's affiliations was omitted.
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http://dx.doi.org/10.1186/s13063-020-04327-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203841PMC
May 2020

Socioeconomic status and survival after stroke - using mediation and sensitivity analyses to assess the effect of stroke severity and unmeasured confounding.

BMC Public Health 2020 Apr 25;20(1):554. Epub 2020 Apr 25.

Department of Statistics, Umeå School of Business, Economics and Statistics, Umeå University, Umeå, Sweden.

Background: Although it has been established that low socioeconomic status is linked to increased risk of death after stroke, the mechanisms behind this link are still unclear. In this study we aim to shed light on the relationship between income level and survival after stroke by investigating the extent to which differences in stroke severity account for differences in survival.

Methods: The study was based on patients registered in Riksstroke (the Swedish stroke register) with first time ischemic stroke (n = 51,159) or intracerebral hemorrhage (n = 6777) in 2009-2012. We used causal mediation analysis to decompose the effect of low income on 3-month case fatality into a direct effect and an indirect effect due to stroke severity. Since causal mediation analysis relies on strong assumptions regarding residual confounding of the relationships involved, recently developed methods for sensitivity analysis were used to assess the robustness of the results to unobserved confounding.

Results: After adjustment for observed confounders, patients in the lowest income tertile had a 3.2% (95% CI: 0.9-5.4%) increased absolute risk of 3-month case fatality after intracerebral hemorrhage compared to patients in the two highest tertiles. The corresponding increase for case fatality after ischemic stroke was 1% (0.4-1.5%). The indirect effect of low income, mediated by stroke severity, was 1.8% (0.7-2.9%) for intracerebral hemorrhage and 0.4% (0.2-0.6%) for ischemic stroke. Unobserved confounders affecting the risk of low income, more severe stroke and case fatality in the same directions could explain the indirect effect, but additional adjustment to observed confounders did not alter the conclusions.

Conclusions: This study provides evidence that as much as half of income-related inequalities in stroke case fatality is mediated through differences in stroke severity. Targeting stroke severity could therefore lead to a substantial reduction in inequalities and should be prioritized. Sensitivity analysis suggests that additional adjustment for a confounder of greater impact than age would be required to considerably alter our conclusions.
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http://dx.doi.org/10.1186/s12889-020-08629-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183587PMC
April 2020

Long-term outcome after ischemic stroke in relation to comorbidity - An observational study from the Swedish Stroke Register (Riksstroke).

Eur Stroke J 2020 Mar 22;5(1):36-46. Epub 2019 Oct 22.

Stroke Policy and Quality Register Research Group, Department of Neurology, Lund University, and Skåne University Hospital, Lund, Sweden.

Purpose: Comorbidity in stroke is common, but comprehensive reports are sparse. We describe prevalence of comorbidity and the prognostic impact on mortality and functional outcome in a large national ischemic stroke cohort.

Methods: We used outcome data from a long-term follow-up survey conducted in 2016 by the Swedish Stroke Register (Riksstroke). Those included in the study were 11 775 pre-stroke functionally independent patients with first-ever ischemic stroke followed up at three months and 12 months (all patients), and three years (2013 cohort) or five years (2011 cohort). Pre-stroke comorbidity data for 16 chronic conditions were obtained from the Swedish National Patient Register, the Swedish Prescribed Drugs Register and the Riksstroke register. Individuals were grouped according to number of conditions: none (0), low (1), moderate (2-3) or high (≥4). Co-occurrence was analysed using hierarchical clustering, and multivariable analyses were used to estimate the prognostic significance of individual conditions.

Results: The proportion of patients without comorbidity was 24.8%; 31.8% had low comorbidity; 33.5% had moderate comorbidity and 9.9% had high comorbidity. At 12 months, the proportion of poor outcome (dead or dependent: mRS ≥3) was 24.8% (no comorbidity), 34.7% (low), 45.2% (moderate) and 59.4% (high). At five years, these proportions were 37.7%, 50.3%, 64.3%, and 81.7%, respectively. There was clustering of cardiovascular conditions and substantial negative effects of dementia, kidney, and heart failure.

Conclusion: Comorbidity is common and has a strong impact on mortality and functional outcome. Our results highlight the need for health systems to shift focus to a comprehensive approach in stroke care that includes multimorbidity as a key component.
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http://dx.doi.org/10.1177/2396987319883154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092731PMC
March 2020

Editorial.

Eur Stroke J 2020 Mar 13;5(1). Epub 2020 Mar 13.

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http://dx.doi.org/10.1177/2396987320912851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092744PMC
March 2020

Global Stroke Statistics 2019.

Int J Stroke 2020 10 9;15(8):819-838. Epub 2020 Mar 9.

Stroke and Ageing Research, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.

Background: Data on stroke epidemiology and availability of hospital-based stroke services around the world are important for guiding policy decisions and healthcare planning.

Aims: To provide the most current incidence, mortality and case-fatality data on stroke and describe current availability of stroke units around the world by country.

Methods: We searched multiple databases (based on our existing search strategy) to identify new original manuscripts and review articles published between 1 June 2016 and 31 October 2018 that met the ideal criteria for data on stroke incidence and case-fatality. For data on the availability of hospital-based stroke services, we searched PubMed for all literature published up until 31 June 2018. We further screened reference lists, citation history of manuscripts and gray literature for this information. Mortality codes for International Classification of Diseases-9 and International Classification of Diseases-10 were extracted from the World Health Organization mortality database for each country providing these data. Population denominators were obtained from the World Health Organization, and when these were unavailable within a two-year period of mortality data, population denominators within a two-year period were obtained from the United Nations. Using country-specific population denominators and the most recent years of mortality data available for each country, we calculated both the crude mortality from stroke and mortality adjusted to the World Health Organization world population.

Results: Since our last report in 2017, there were two countries with new incidence studies, China ( = 1) and India ( = 2) that met the ideal criteria. New data on case-fatality were found for Estonia and India. The most current mortality data were available for the year 2015 (39 countries), 2016 (43 countries), and 2017 (7 countries). No new data on mortality were available for six countries. Availability of stroke units was noted for 63 countries, and the proportion of patients treated in stroke units was reported for 35/63 countries.

Conclusion: Up-to-date data on stroke incidence, case-fatality, and mortality statistics provide evidence of variation among countries and changing magnitudes of burden among high and low-middle income countries. Reporting of hospital-based stroke units remains limited and should be encouraged.
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http://dx.doi.org/10.1177/1747493020909545DOI Listing
October 2020

Update on the EFFECTS study of fluoxetine for stroke recovery: a randomised controlled trial in Sweden.

Trials 2020 Feb 28;21(1):233. Epub 2020 Feb 28.

Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Studies have suggested that fluoxetine might improve neurological recovery after stroke, but the results remain inconclusive. The EFFECTS (Efficacy oF Fluoxetine - a randomisEd Controlled Trial in Stroke) reached its recruitment target of 1500 patients in June 2019. The purpose of this article is to present all amendments to the protocol and describe how we formed the EFFECTS trial collaboration in Sweden.

Methods: In this investigator-led, multicentre, parallel-group, randomised, placebo-controlled trial, we enrolled non-depressed stroke patients aged 18 years or older between 2 and 15 days after stroke onset. The patients had a clinical diagnosis of stroke (ischaemic or intracerebral haemorrhage) with persisting focal neurological deficits. Patients were randomised to fluoxetine 20 mg or matching placebo capsules once daily for 6 months.

Results: Seven amendments were made and included clarification of drug interaction between fluoxetine and metoprolol and the use of metoprolol for severe heart failure as an exclusion criterion, inclusion of data from central Swedish registries and the Swedish Stroke Register, changes in informed consent from patients, and clarification of design of some sub-studies. EFFECTS recruited 1500 patients at 35 centres in Sweden between 20 October 2014 and 28 June 2019. We plan to unblind the data in January 2020 and report the primary outcome in May 2020.

Conclusion: EFFECTS will provide data on the safety and efficacy of 6 months of treatment with fluoxetine after stroke in a Swedish health system setting. The data from EFFECTS will also contribute to an individual patient data meta-analysis.

Trial Registration: EudraCT 2011-006130-16. Registered on 8 August 2014. ISRCTN, ISRCTN13020412. Registered on 19 December 2014. ClinicalTrials.gov: NCT02683213. Retrospectively registered on 2 February 2016.
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http://dx.doi.org/10.1186/s13063-020-4124-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048055PMC
February 2020

The nature stroke study; NASTRU: A randomized controlled trial of nature-based post-stroke fatigue rehabilitation.

J Rehabil Med 2020 Feb;52(2):jrm00020

Objective: To determine whether nature-based rehabilitation, as an add-on to standard care, has a long-term influence on post-stroke fatigue, perceived value of everyday occupations, disability, health-related quality of life, anxiety, and depression at follow-up 8 and 14 months after randomization.

Design: Single-blinded, 2-armed, randomized controlled trial.

Methods: Stroke survivors, identified through routine 3-month follow-up visit (sub-acute) or medical records (chronic stroke > 1 year previously), were randomized to standard care + nature-based rehabilitation (intervention group) or standard care alone (control group). Blinded evaluations were conducted at follow-up 8 and 14 months after randomization, for the following outcomes: post-stroke fatigue (Mental Fatigue Scale; MFS), perceived value of everyday occupations (Occupational value instrument with pre-defined items), disability (modified Rankin Scale; mRS), health-related quality of life (Euro-QoL-5 Demension Questionnaire), anxiety (Hospital Anxiety and Depression Scale; HAD) and depression (HAD).

Results: Approximately one-quarter of the screened patients were eligible for inclusion in the study; of these, half agreed to participate; a final total of 101 patients were randomized (mean age 67 years, 60% female). The patients with sub-acute stroke were highly compliant with the intervention. The participants in both the intervention and control groups improved, However, no statistically significant differences in improvement were found between the intervention and control groups for any of the outcome measures. Fatigue decreased to a value below the suggested cut-off for mental fatigue (< 10.5) in the intervention group, but not in the control group.

Conclusion: Nature-based rehabilitation is feasible and well tolerated. A larger randomized controlled trial is warranted.
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http://dx.doi.org/10.2340/16501977-2652DOI Listing
February 2020

International Impact of .

Stroke 2020 Mar 19;51(3):1036-1039. Epub 2020 Feb 19.

From the Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Australia (S.M.D., G.A.D.).

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http://dx.doi.org/10.1161/STROKEAHA.119.028422DOI Listing
March 2020

Relationship of White Matter Lesions with Intracerebral Hemorrhage Expansion and Functional Outcome: MISTIE II and CLEAR III.

Neurocrit Care 2020 10;33(2):516-524

Department of Clinical Sciences Lund, Neurology, Skåne University Hospital, Lund University, Lund, Sweden.

Background/objective: Intracerebral hemorrhage (ICH) patients commonly have concomitant white matter lesions (WML) which may be associated with poor outcome. We studied if WML affects hematoma expansion (HE) and post-stroke functional outcome in a post hoc analysis of patients from randomized controlled trials.

Methods: In ICH patients from the clinical trials MISTIE II and CLEAR III, WML grade on diagnostic computed tomography (dCT) scan (dCT, < 24 h after ictus) was assessed using the van Swieten scale (vSS, range 0-4). The primary outcome for HE was > 33% or > 6 mL ICH volume increase from dCT to the last pre-randomization CT (< 72 h of dCT). Secondary HE outcomes were: absolute ICH expansion, > 10.4 mL total clot volume increase, and a subgroup analysis including patients with dCT < 6 h after ictus using the primary HE definition of > 33% or > 6 mL ICH volume increase. Poor functional outcome was assessed at 180 days and defined as modified Rankin Scale (mRS) ≥ 4, with ordinal mRS as a secondary endpoint.

Results: Of 635 patients, 55% had WML grade 1-4 at dCT (median 2.2 h from ictus) and 13% had subsequent HE. WML at dCT did not increase the odds for primary or secondary HE endpoints (P ≥ 0.05) after adjustment for ICH volume, intraventricular hemorrhage volume, warfarin/INR > 1.5, ictus to dCT time in hours, age, diabetes mellitus, and thalamic ICH location. WML increased the odds for having poor functional outcome (mRS ≥ 4) in univariate analyses (vSS 4; OR 4.16; 95% CI 2.54-6.83; P < 0.001) which persisted in multivariable analyses after adjustment for HE and other outcome risk factors.

Conclusions: Concomitant WML does not increase the odds for HE in patients with ICH but increases the odds for poor functional outcome.

Clinical Trial Registration: http://www.clinicaltrials.gov trial-identifiers: NCT00224770 and NCT00784134.
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http://dx.doi.org/10.1007/s12028-020-00916-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416541PMC
October 2020

Editorial.

Eur Stroke J 2019 Sep 9;4(3):196-197. Epub 2019 Sep 9.

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http://dx.doi.org/10.1177/2396987319869776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960685PMC
September 2019
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