Diverging trends in survival and functional outcome between males and females after intracerebral hemorrhage.

Background Compared to ischemic stroke, sex differences in patient outcome following intracerebral hemorrhage (ICH) is underreported. We aimed to determine sex differences in mortality and functional outcome in a large, unselected Swedish cohort. Methods In this observational study, data on 22789 patients with spontaneous ICH registered in the Swedish Stroke Register between 2012-2019 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 (3820/10405) and 31.7% in males (3929/12384) (female Hazard Ratio (HR) 1.20 95%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, 90-day functional outcome in prestroke independent patients was worse in females compared to males (OR 1.27 95%CI: 1.16-1.40). Conclusion In this large observational study, despite a lower 90-day mortality, 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.

Diagnostic accuracy and radiological validation of intracerebral hemorrhage diagnosis in the Swedish Stroke Register (Riksstroke).

BACKGROUND AND PURPOSE: National quality registries for stroke care operate under the assumption that the included patients are correctly diagnosed. We aimed to validate the clinical diagnosis of spontaneous intracerebral hemorrhage (ICH) in Riksstroke (RS) by evaluating radiological data from a large, unselected ICH population. METHODS: We conducted a retrospective, multicenter study including all ICH patients registered in RS between 2016 and 2020 residing in Skåne County in Sweden (1.41 million inhabitants). Radiological data from first imaging were evaluated for the presence of spontaneous ICH. Other types of bleeds were registered if a spontaneous ICH was not identified on imaging. The radiological evaluation was independently performed by one radiology fellow and one senior neuroradiologist. RESULTS: Between 2016 and 2020, 1784 ICH cases were registered in RS, of which 1655 (92.8%) had a radiological diagnosis consistent with spontaneous ICH. In the 129 (7.2%) remaining cases, the radiological diagnosis was instead traumatic bleed (n = 80), subarachnoid hemorrhage (n = 15), brain tumor bleed (n = 14), ischemic lesion with hemorrhagic transformation (n = 14), ischemic lesion (n = 3), or no bleed at all (n = 3). There was a higher degree of incorrect coding in the older age groups. CONCLUSION: At radiological evaluation, 92.8% of ICH diagnoses in RS were consistent with spontaneous ICH, yielding a high rate of agreement that strengthens the validity of the diagnostic accuracy in the register, justifying the use of high coverage quality register data for epidemiological purposes. The most common coding error was traumatic bleeds that were classified as spontaneous ICH.

Twenty years on from the introduction of the high risk strategy for stroke and cardiovascular disease prevention: a systematic scoping review.

BACKGROUND AND PURPOSE: Early this century, the high risk strategy of primary stroke and cardiovascular disease (CVD) prevention for individuals shifted away from identifying (and treating, as appropriate) all at-risk individuals towards identifying and treating individuals who exceed arbitrary thresholds of absolute CVD risk. The public health impact of this strategy is uncertain. METHODS: In our systematic scoping review, the electronic databases (Scopus, MEDLINE, Embase, Google Scholar, Cochrane Library) were searched to identify and appraise publications related to primary CVD/stroke prevention strategies and their effectiveness published in any language from January 1990 to August 2023. RESULTS: No published randomized controlled trial was found on the effectiveness of the high CVD risk strategy for primary stroke/CVD prevention. Targeting high CVD risk individuals excludes a large proportion of the population from effective blood-pressure-lowering and lipid-lowering treatment and effective CVD prevention. There is also evidence that blood pressure lowering and lipid lowering are beneficial irrespective of blood pressure and cholesterol levels and irrespective of absolute CVD risk and that risk-stratified pharmacological management of blood pressure and lipids to only high CVD risk individuals leads to significant underuse of blood-pressure-lowering and lipid-lowering medications in individuals otherwise eligible for such treatment. CONCLUSIONS: Primary stroke and CVD prevention needs to be done in all individuals with increased risk of CVD/stroke. Pharmacological management of blood pressure and blood cholesterol should not be solely based on the high CVD risk treatment thresholds. International guidelines and global strategies for primary CVD/stroke prevention need to be revised.

Early Versus Delayed Non-Vitamin K Antagonist Oral Anticoagulant Therapy After Acute Ischemic Stroke in Atrial Fibrillation (TIMING): A Registry-Based Randomized Controlled Noninferiority Study.

BACKGROUND: There are no evidence-based recommendations on the optimal time point to initiate non-vitamin K antagonist oral anticoagulants (NOACs) after acute ischemic stroke in patients with atrial fibrillation. We aimed to investigate the efficacy and safety of early versus delayed initiation of NOAC in these patients. METHODS: TIMING (Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation) was a registry-based, randomized, noninferiority, open-label, blinded end-point study at 34 stroke units using the Swedish Stroke Register for enrollment and follow-up. Within 72 hours from stroke onset, patients were randomized to early (≤4 days) or delayed (5-10 days) NOAC initiation, with choice of NOAC at the investigators' discretion. The primary outcome was the composite of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality at 90 days. The prespecified noninferiority margin was 3%. Secondary outcomes included the individual components of the primary outcome. RESULTS: Between April 2, 2017, and December 30, 2020, 888 patients were randomized to either early (n=450) or delayed (n=438) initiation of NOAC. No patient was lost to 90-day follow-up. Mean age was 78.3 years (SD, 9.9 years); 46.2% were women; 49.1% had previously known atrial fibrillation; and 17.5% prior stroke. The primary outcome occurred in 31 patients (6.89%) assigned to early initiation and in 38 patients (8.68%) assigned to delayed NOAC initiation (absolute risk difference, -1.79% [95% CI, -5.31% to 1.74%]; Pnoninferiority=0.004). Ischemic stroke rates were 3.11% and 4.57% (risk difference, -1.46% [95% CI, -3.98% to 1.07%]) and all-cause mortality rates were 4.67% and 5.71% (risk difference, -1.04% [95% CI, -3.96% to 1.88%]) in the early and delayed groups, respectively. No patient in either group experienced symptomatic intracerebral hemorrhage. CONCLUSIONS: Early initiation was noninferior to delayed start of NOAC after acute ischemic stroke in patients with atrial fibrillation. Numerically lower rates of ischemic stroke and death and the absence of symptomatic intracerebral hemorrhages implied that the early start of NOAC was safe and should be considered for acute secondary stroke prevention in patients eligible for NOAC treatment. REGISTRATION: URL: http://www. CLINICALTRIALS: gov; Unique identifier: NCT02961348.

Stroke Learning Health Systems: A Topical Narrative Review With Case Examples.

To our knowledge, the adoption of Learning Health System (LHS) concepts or approaches for improving stroke care, patient outcomes, and value have not previously been summarized. This topical review provides a summary of the published evidence about LHSs applied to stroke, and case examples applied to different aspects of stroke care from high and low-to-middle income countries. Our attempt to systematically identify the relevant literature and obtain real-world examples demonstrated the dissemination gaps, the lack of learning and action for many of the related LHS concepts across the continuum of care but also elucidated the opportunity for continued dialogue on how to study and scale LHS advances. In the field of stroke, we found only a few published examples of LHSs and health systems globally implementing some selected LHS concepts, but the term is not common. A major barrier to identifying relevant LHS examples in stroke may be the lack of an agreed taxonomy or terminology for classification. We acknowledge that health service delivery settings that leverage many of the LHS concepts do so operationally and the lessons learned are not shared in peer-reviewed literature. It is likely that this topical review will further stimulate the stroke community to disseminate related activities and use keywords such as learning health system so that the evidence base can be more readily identified.

Diverging Trends in the Incidence of Spontaneous Intracerebral Hemorrhage in Sweden 2010-2019: An Observational Study from the Swedish Stroke Register (Riksstroke).

INTRODUCTION: Although ischemic stroke incidence has decreased in Sweden over the past decade, trends in spontaneous intracerebral hemorrhage (ICH) incidence are less well delineated. In this time period, there has been a dramatic increase in use of oral anticoagulants (OAC). The aim of our study was to investigate incidence trends in spontaneous first-ever ICH in Sweden between 2010 and 2019, with a focus on non-OAC-associated and OAC-associated ICH. METHODS: We included patients (≥18 years) with first-ever ICH registered in the hospital-based Swedish Stroke Register (Riksstroke) 2010-2019. Data were stratified by non-OAC and OAC ICH and analyzed for 2010-2012, 2013-2016, and 2017-2019. Incidence rates are shown as crude and age-specific per 100,000 person-years. RESULTS: Between 2010 and 2019, 22,289 patients with first-ever ICH were registered; 18,325 (82.2%) patients with non-OAC ICH and 3,964 (17.8%) patients with OAC ICH. Annual crude incidence (per 100,000) of all first-ever ICH decreased by 10% from 29.5 (95% CI 28.8-30.3) to 26.7 (95% CI 26.0-27.3) between 2010-2012 and 2017-2019. The crude incidence rate of non-OAC ICH decreased by 20% from 25.7 (95% CI 25.0-26.3) to 20.7 (95% CI 20.1-21.2), whereas OAC ICH increased by 56% from 3.86 (95% CI 3.61-4.12) to 6.01 (95% CI 5.70-6.32). The proportion of OAC ICH of all first-ever ICH increased between 2010-2012 and 2017-2019 from 13.1% to 22.5% (p < 0.001). Proportional changes were largest in the age group ≥85 years with a decrease in non-OAC ICH by 32% from 155 (95% CI 146-164) to 106 (95% CI 98.6-113) and an increase in OAC ICH by 155% from 25.7 (95% CI 22.1-29.4) to 65.5 (95% CI 59.9-71.2). CONCLUSION: Incidence of first-ever ICH in Sweden decreased by 10% between 2010 and 2019. We found diverging trends with a 20% decrease in non-OAC-associated ICH and a 56% increase in OAC-associated ICH. Further research on ICH epidemiology, analyzing non-OAC and OAC-associated ICH separately, is needed to follow up these diverging trends including underlying risk factors.

Accuracy of automated intracerebral hemorrhage volume measurement on non-contrast computed tomography: a Swedish Stroke Register cohort study.

PURPOSE: Hematoma volume is the strongest predictor of patient outcome after intracerebral hemorrhage (ICH). The aim of this study was to validate novel fully automated software for quantification of ICH volume on non-contrast computed tomography (CT). METHODS: The population was defined from the Swedish Stroke Register (RS) and included all patients with an ICH diagnosis during 2016-2019 in Region Skåne. Hemorrhage volume on their initial head CT was measured using ABC/2 and manual segmentation (Sectra IDS7 volume measurement tool) and the automated volume quantification tool (qER-NCCT) by Qure.ai. The first 500 were examined by two independent readers. RESULTS: A total of 1649 ICH patients were included. The qER-NCCT had 97% sensitivity in identifying ICH. In total, there was excellent agreement between volumetric measurements of ICH volumes by qER-NCCT and manual segmentation by interclass correlation (ICC = 0.96), and good agreement (ICC = 0.86) between qER-NCCT and ABC/2 method. The qER-NCCT showed volume underestimation, mainly in large (> 30 ml) heterogenous hemorrhages. Interrater agreement by (ICC) was 0.996 (95% CI: 0.99-1.00) for manual segmentation. CONCLUSION: Our study showed excellent agreement in volume quantification between the fully automated software qER-NCCT and manual segmentation of ICH on NCCT. The qER-NCCT would be an important additive tool by aiding in early diagnostics and prognostication for patients with ICH and in provide volumetry on a population-wide level. Further refinement of the software should address the underestimation of ICH volume seen in a portion of large, heterogenous, irregularly shaped ICHs.

Measuring Stroke Quality: Methodological Considerations in Selecting, Defining, and Analyzing Quality Measures.

Knowledge about stroke and its management is growing rapidly and stroke systems of care must adapt to deliver evidence-based care. Quality improvement initiatives are essential for translating knowledge from clinical trials and recommendations in guidelines into routine clinical practice. This review focuses on issues central to the measurement of the quality of stroke care, including selection and definition of quality measures, identification of the eligible patient cohorts, optimization of data quality, and considerations for data analysis and interpretation.

Epidemiology of First and Recurrent Ischemic Stroke in Sweden 2010-2019: A Riksstroke Study.

INTRODUCTION: Ischemic stroke incidence appears to have decreased during the last decades, but most studies focus on the first-ever events and epidemiological data on recurrent stroke are scarce. The aim of our study was to investigate trends in incidence, risk factors, and medication in patients with first-ever and recurrent ischemic stroke between 2010 and 2019 in Sweden. METHODS: We included patients (≥18 years old) with ischemic stroke registered in the hospital-based Swedish Stroke Register (Riksstroke) 2010-2019. The coverage of Riksstroke was consistently high (about 90%) during this period. Data were stratified by first-ever and recurrent ischemic stroke in three different time periods (2010-2012, 2013-2016, and 2017-2019) and shown as crude and age-specific incidence rates per 100,000 person-years. Statistics Sweden provided census data on the Swedish population in different age groups. RESULTS: During the study period, 201,316 cases of ischemic stroke were registered in Riksstroke, including 153,865 (76.4%) cases of first-ever ischemic stroke and 46,248 (23.0%) cases of recurrent ischemic stroke (0.6% of cases unclassified). The crude incidence of first-ever ischemic stroke decreased by 17% from 216 (95% CI 214-218) to 179 (95% CI 177-181) between 2010-2012 and 2017-2019, whereas recurrent ischemic stroke decreased by 33% from 72 (95% CI 71-73) to 48 (95% CI 47-49). Between these time periods, diminishing ischemic stroke incidence was seen in all age groups with highest decline noted in those aged 75-84 years (928 [95% CI 914-943] to 698 [95% CI 686-709]; -25% in first-ever ischemic stroke and 361 [95% CI 351-370] to 219 [95% CI 213-226]; -39% in recurrent ischemic stroke) and ≥85 years (1,674 [95% CI 1,645-1,703] to 1,295 [95% CI 1,270-1,320]; -23% in first-ever ischemic stroke and 683 [95% CI 664-702] to 423 [95% CI 409-437]; -38% in recurrent ischemic stroke). Treatment with anticoagulants in patients with atrial fibrillation and lipid-lowering drugs increased considerably in patients with first-ever and recurrent ischemic stroke both at admission and discharge during the study period. CONCLUSION: Whereas both first-ever and recurrent ischemic stroke rates declined in Sweden between 2010 and 2019, the proportional decline was almost double for recurrent ischemic stroke than for first-ever ischemic stroke and most pronounced in the elderly. Increased use of secondary preventive drugs, in particular anticoagulants in atrial fibrillation, appears to have contributed, but further studies on precise causes for the decline in recurrent ischemic stroke are needed.

Patient factors associated with receiving reversal therapy in oral anticoagulant-related intracerebral hemorrhage.

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.

Endovascular therapy in basilar artery occlusion in Sweden 2016-2019-a nationwide, prospective registry study.

PURPOSE: We present the first nationwide study on endovascular therapy for basilar artery occlusion (BAO) from early hospital management to 3-month outcome. METHODS: Data were collected on all acute ischaemic stroke patients registered 2016-2019 in the two national quality registers for stroke care and endovascular therapy (EVT), receiving EVT for BAO and subclassified into proximal, middle and distal. RESULTS: In all, 251 patients were included: 69 proximal, 73 middle and 109 distal BAO. Patients with proximal BAO were younger (66, middle 71, distal 76, p < 0.0001), less often female (27.5%, middle 47.9%, distal 47.7%, p = 0.015), more often smokers (28.6%, middle 20.3%, distal 11.5%, p < 0.0001), and fewer had atrial fibrillation (13.2%, middle 24.7%, distal 48.6%, p < 0.0001). Level of consciousness and NIHSS score did not differ by BAO subtype and 52.2% were alert on admission. Time from groin puncture to revascularization was significantly longer in patients with proximal BAO (71, middle 46, distal 42 min, p < 0.0001), and angioplasty and/or stenting was more often performed in patients with proximal (43.4%) and middle (27.4%) than distal (6.4%) BAO (p < 0.0001). Cumulative 90-day mortality was 38.6% (proximal 50.7%, middle 32.9%, distal 34.9%, p = 0.02). Older and pre-stroke dependent patients had higher mortality, as did patients in whom angioplasty/stenting was performed. CONCLUSION: We confirm a serious outcome in BAO despite endovascular therapies, and demonstrate important differences relating to occlusion location in baseline characteristics, procedural time, therapeutic measures and outcome. Further in-depth analyses of factors affecting outcome in BAO are warranted.

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

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.

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

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.

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

Background and Purpose: The EFFECTS (Efficacy of Fluoxetine­a Randomised Controlled Trial in Stroke) recently reported that 20 mg fluoxetine once daily for 6 months after acute stroke did not improve functional outcome but reduced depression and increased fractures and hyponatremia at 6 months. The purpose of this predefined secondary analysis was to identify if any effects of fluoxetine were maintained or delayed over 12 months. Methods: EFFECTS was an investigator-led, randomized, placebo-controlled, double-blind, parallel group trial in Sweden that enrolled adult patients with stroke. Patients were randomized to 20 mg oral fluoxetine or matching placebo for 6 months and followed for another 6 months. The primary outcome was functional outcome (modified Rankin Scale), at 6 months. Predefined secondary outcomes for these analyses included the modified Rankin Scale, health status, quality of life, fatigue, mood, and depression at 12 months. Results: One thousand five hundred patients were recruited from 35 centers in Sweden between 2014 and 2019; 750 were allocated fluoxetine and 750 placebo. At 12 months, modified Rankin Scale data were available in 715 (95%) patients allocated fluoxetine and 712 (95%) placebo. The distribution of modified Rankin Scale categories was similar in the 2 groups (adjusted common odds ratio, 0.92 [95% CI, 0.76­1.10]). Patients allocated fluoxetine scored worse on memory with a median value of 89 (interquartile range, 75­100) versus 93 (interquartile range, 82­100); P=0.0021 and communication 93 (interquartile range, 82­100) versus 96 (interquartile range, 86­100); P=0.024 domains of the Stroke Impact Scale compared with placebo. There were no other differences in secondary outcomes. Conclusions: Fluoxetine after acute stroke had no effect on functional outcome at 12 months. Patients allocated fluoxetine scored worse on memory and communication on the Stroke Impact Scale compared with placebo, but this is likely to be due to chance. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02683213.

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

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.

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

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.

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

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.

Return to work after stroke: A Swedish nationwide registry-based study.

OBJECTIVES: A substantial proportion of individuals with stroke are of working age. After stroke, it is important to return to work (RTW), both for the individual's satisfaction with life and economically for society. The current comprehensive, long-term study aimed at investigating in what time period the RTW continues after stroke and what factors could predict RTW. MATERIALS AND METHODS: All individuals registered in the registry Riksstroke with stroke in Sweden at ages 18-58 years during 2011 were eligible for participation. RTW was based on sickness absence data from the Social Insurance Agency covering 1 year prestroke to 5 years post-stroke. Time to RTW was analyzed with Kaplan-Meier curves. Potential predictors of RTW were analyzed with Cox regression and logistic regression. RESULTS: For RTW analyses, 1695 participants were included. Almost 50% RTW within 3 months, 70% within 1 year, and 80% within 2 years post-stroke. However, the RTW continued for several years, with a total of 85% RTW. Predictors of favorable time to RTW were male sex, ischemic stroke, and long university education compared with primary school education. Predictors of unfavorable times to RTW were higher stroke severity, defined by the level of consciousness, and older ages. Participants with self-expectations of RTW 1 year post-stroke had higher odds of RTW within 5 years. CONCLUSIONS: The RTW continues for a longer time after stroke than previously known. Both self-expectations and demographical, socioeconomic, stroke-related factors were important predictors of RTW. This knowledge could assist healthcare professionals to individualize the rehabilitation post-stroke.

Completeness of case ascertainment in Swedish hospital-based stroke registers.

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.

Genome-wide association study of cerebral small vessel disease reveals established and novel loci.

Intracerebral haemorrhage and small vessel ischaemic stroke (SVS) are the most acute manifestations of cerebral small vessel disease, with no established preventive approaches beyond hypertension management. Combined genome-wide association study (GWAS) of these two correlated diseases may improve statistical power to detect novel genetic factors for cerebral small vessel disease, elucidating underlying disease mechanisms that may form the basis for future treatments. Because intracerebral haemorrhage location is an adequate surrogate for distinct histopathological variants of cerebral small vessel disease (lobar for cerebral amyloid angiopathy and non-lobar for arteriolosclerosis), we performed GWAS of intracerebral haemorrhage by location in 1813 subjects (755 lobar and 1005 non-lobar) and 1711 stroke-free control subjects. Intracerebral haemorrhage GWAS results by location were meta-analysed with GWAS results for SVS from MEGASTROKE, using 'Multi-Trait Analysis of GWAS' (MTAG) to integrate summary data across traits and generate combined effect estimates. After combining intracerebral haemorrhage and SVS datasets, our sample size included 241 024 participants (6255 intracerebral haemorrhage or SVS cases and 233 058 control subjects). Genome-wide significant associations were observed for non-lobar intracerebral haemorrhage enhanced by SVS with rs2758605 [MTAG P-value (P) = 2.6 × 10-8] at 1q22; rs72932727 (P = 1.7 × 10-8) at 2q33; and rs9515201 (P = 5.3 × 10-10) at 13q34. In the GTEx gene expression library, rs2758605 (1q22), rs72932727 (2q33) and rs9515201 (13q34) are significant cis-eQTLs for PMF1 (P = 1 × 10-4 in tibial nerve), NBEAL1, FAM117B and CARF (P < 2.1 × 10-7 in arteries) and COL4A2 and COL4A1 (P < 0.01 in brain putamen), respectively. Leveraging S-PrediXcan for gene-based association testing with the predicted expression models in tissues related with nerve, artery, and non-lobar brain, we found that experiment-wide significant (P < 8.5 × 10-7) associations at three genes at 2q33 including NBEAL1, FAM117B and WDR12 and genome-wide significant associations at two genes including ICA1L at 2q33 and ZCCHC14 at 16q24. Brain cell-type specific expression profiling libraries reveal that SEMA4A, SLC25A44 and PMF1 at 1q22 and COL4A1 and COL4A2 at 13q34 were mainly expressed in endothelial cells, while the genes at 2q33 (FAM117B, CARF and NBEAL1) were expressed in various cell types including astrocytes, oligodendrocytes and neurons. Our cross-phenotype genetic study of intracerebral haemorrhage and SVS demonstrates novel genome-wide associations for non-lobar intracerebral haemorrhage at 2q33 and 13q34. Our replication of the 1q22 locus previous seen in traditional GWAS of intracerebral haemorrhage, as well as the rediscovery of 13q34, which had previously been reported in candidate gene studies with other cerebral small vessel disease-related traits strengthens the credibility of applying this novel genome-wide approach across intracerebral haemorrhage and SVS.