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Objective: To determine predictors of direct enteral tube (DET) placement after acute stroke.Methods: We used the Ontario Stroke Registry to identify patients who received direct enteral tubes (gastrostomy or jejunostomy) during hospital stay after acute ischemic stroke or intracerebral hemorrhage from July 1, 2003 to March 31, 2013. We used multivariable logistic regression to identify predictors of receiving DET after stroke.Results: Among 38,192 patients with acute stroke who met inclusion criteria, 1851 (4.9%) had DET placement during admission. We identified multiple variables significantly associated with DET placement, spanning patient demographics, comorbid illnesses, clinical, and hospital factors. The strongest predictors of receiving DET were stroke severity (adjusted odds ratio [aOR] 4.77 for severe versus mild stroke, 95% confidence interval [CI] 4.20-5.41), receiving a swallowing test within 72 hours (aOR 3.46, 95% CI 3.0-3.99), and in-hospital stroke (aOR 2.07, 95% CI 1.57-2.72).Conclusions: There are a number of predictors of DET placement within multiple domains. These findings may facilitate discussions around the possibility of requiring DET during admission. Further work is required to improve patient selection and timing of DET placement after acute stroke. [ABSTRACT FROM AUTHOR]

To examine whether the association of co-morbidity with mortality after acute stroke is influenced by stroke type, age, sex, or time since stroke. We conducted a province-wide population-based study using linked administrative databases to identify all admissions for acute stroke between 2007-2018 in Alberta, Canada. We used Cox proportional hazard models to determine the association of severe co-morbidity based on the Charlson Co-morbidity Index with 1-year mortality after stroke, assessing for effect modification by stroke type, age, and sex, and with adjustment for estimated stroke severity, comprehensive stroke centre care, hypertension, atrial fibrillation, and year of study. We used a piecewise model to analyze the impact of co-morbidity across four time periods. We had 28,672 patients in our final cohort (87.8% ischemic stroke). The hazard of mortality with severe co-morbidity was higher for individuals with ischemic stroke (adjusted hazard ratio [aHR] 2.20, 95% CI 2.07-2.32) compared to those with intracerebral hemorrhage (aHR 1.70, 95% CI 1.51-1.92; p int <0.001), and higher in individuals under age 75 (aHR 3.20, 95% CI 2.90-3.53) compared to age ≥75 (aHR 1.93, 95% CI 1.82-2.05, p int <0.001). There was no interaction by sex. The hazard ratio increased in a graded fashion at younger ages and was higher after the first 30 days of acute stroke. There was a stronger association between co-morbidity and mortality at younger age and in the subacute phase of stroke. Further research is needed to determine the reason for these findings and identify ways to improve outcomes among those with stroke and co-morbid conditions at young age. [ABSTRACT FROM AUTHOR]

Background and Purpose: Despite recent declines in stroke mortality in high-income countries, the incidence and mortality of stroke have increased in many low- and middle-income countries. Population-based information on stroke in such countries is a research priority to address this rising trend. This study was designed to evaluate 5-year stroke mortality and its associated factors.Methods: During a 12-month period beginning from November 2006, 624 patients with first-ever stroke (FES) living in Mashhad, Iran, were recruited and followed longitudinally. Kaplan-Meier analyses were used to determine the cumulative risk of death. Prognostic variables associated with death were assessed using a Cox proportional hazard, backward logistic regression model.Results: The 5-year cumulative risk of death was 53.8% for women and 60.5% for men (log rank = .1). The most frequent causes of death were stroke (41.2%), myocardial infarction/vascular diseases (16.4%), and pneumonia (14.2%). In multivariable Cox proportional hazard analysis, male gender (hazard ratio [HR]: 1.29, 95% confidence interval [CI]: 1.01-1.64), age (HR: 1.04, 95% CI: 1.03-1.05, per 1-year increase), National Institute of Health Stroke Scale score at admission (HR: 1.11, 95% CI: 1.09-1.12, per 1-point increase), atrial fibrillation (HR: 1.78, CI: 1.24-2.54), and education < 12 years (HR: 1.61, 95% CI: 1.08-2.4) were associated with greater 5-year case fatality.Conclusions: Long-term case fatality following stroke in Iran is greater than that observed in many high-income countries. Targeting strategies to reduce the poor outcome following stroke, such as treating AF, is likely to reduce this disparate outcome. [ABSTRACT FROM AUTHOR]

Background: Population-based data regarding stroke among women are scarce in developing countries. This study was designed to determine whether sex differences exist in stroke incidence, mortality, and recurrence.Methods: The Mashhad Stroke Incidence Study is a population-based cohort study in Iran. For a period of 1 year, all patients with stroke in 3 geographical regions in Mashhad were recruited and then followed up for 5 years. Age- and sex-specific crude incidence rates were standardized to the World Health Organization New World Population. Male-to-female incidence rate ratios were assessed for all age groups and all subtypes of first-ever stroke (FES).Results: The annual crude incidence rate of FES (per 100,000 population) was similar in men (144; 95% confidence interval [CI]: 129-160) and women (133; 95% CI: 119-149). Standardized FES annual incidence rates were 239 (95% CI: 213-267) for men and 225 (95% CI 200-253) for women, both greater than in most western countries. There were no significant differences in stroke recurrence or case-fatality between women and men during early and long-term follow-up.Conclusion: The similar incidence of stroke between men and women highlights the importance of equally prioritizing adequate preventive strategies for both sexes. The greater relative incidence of stroke in women in Mashhad compared with other countries warrants improvement of primary and secondary stroke prevention. [ABSTRACT FROM AUTHOR]

Background: Outcomes after stroke in those with diabetes are not well characterized, especially by sex and age. We sought to calculate the sex- and age-specific risk of cardiovascular outcomes after ischemic stroke among those with diabetes.Methods: Using population-based demographic and administrative health-care databases in Ontario, Canada, all patients with diabetes hospitalized with index ischemic stroke between April 1, 2002, and March 31, 2012, were followed for death, stroke, and myocardial infarction (MI). The Kaplan-Meier survival analysis and Fine-Gray competing risk models estimated hazards of outcomes by sex and age, unadjusted and adjusted for demographics and vascular risk factors.Results: Among 25,495 diabetic patients with index ischemic stroke, the incidence of death was higher in women than in men (14.08 per 100 person-years [95% confidence interval [CI], 13.73-14.44] versus 11.89 [11.60-12.19]) but was lower after adjustment for age and other risk factors (adjusted hazard ratio [HR], .95 [.92-.99]). Recurrent stroke incidence was similar by sex, but men were more likely to be readmitted for MI (1.99 per 100 person-years [1.89-2.10] versus 1.58 [1.49-1.68] among females). In multivariable models, females had a lower risk of readmission for any event (HR, .96 [95% CI, .93-.99]).Conclusions: In this large, population-based, retrospective study among diabetic patients with index stroke, women had a higher unadjusted death rate but lower unadjusted incidence of MI. In adjusted models, females had a lower death rate compared with males, although the increased risk of MI among males persisted. These findings confirm and quantify sex differences in outcomes after stroke in patients with diabetes. [ABSTRACT FROM AUTHOR]

Background: Advances in acute management and secondary prevention have reduced mortality and early recurrent risk after stroke and transient ischemic attack (TIA). However, whether improved outcomes are sustained long term among those without early adverse complications is not clear. We describe trends in long-term mortality and morbidity in patients with ischemic stroke or TIA who are clinically stable at 90 days.Methods: This is a longitudinal cohort registry study (2003-2013) of patients presenting to stroke centers in Ontario, Canada, with a stroke or TIA, with no hospitalization, stroke, myocardial infarction (MI), institutionalization, or death within 90 days (N = 26,698). Primary outcomes were 1-, 3-, and 5-year age-adjusted composite rates of death, stroke or MI, and institutionalization, and secondary analyses evaluated outcomes individually. Trend tests were used to evaluate change over time.Results: One-year adjusted composite rates decreased from 9.3% in 2003 to 7.4% in 2012 (trend test P = .02). Significant decreases in 3-year (P < .001) and 5-year (P = .002) composite rates were also observed. Rates of recurrent stroke decreased at 1 and 3 years (P < .01), but not 5 years (P = .21), whereas death rates declined across follow-up times. Conversely, rates of institutionalization increased at 3 and 5 years (P < .01).Conclusions: Long-term mortality and morbidity post stroke and TIA have declined, confirming trends for improved long-term outcomes for patients clinically stable during the initial high-risk period. However, increased long-term rates of institutionalization also suggest that stroke and TIA patients are at risk of long-term functional decline, despite improved clinical outcomes. Further studies evaluating challenges for sustaining functional gains after stroke and TIA are required. [ABSTRACT FROM AUTHOR]

Abstract: Background: Studies of potential gender differences in stroke care and outcomes have yielded inconsistent findings. The Project for an Ontario Women’s Health Evidence-based Report study measured established stroke care indicators in a large, representative sample of women and men with stroke or transient ischemic attack (TIA) admitted to acute care institutions in the province of Ontario, Canada. Methods: The Registry of the Canadian Stroke Network performs a biennial audit on a random sample of 20% of patients with stroke or TIA seen at more than 150 acute care institutions across Ontario. We used data from the 2004/05 audit to compare stroke care by gender, with stratification by age and neighborhood income. Results: The sample consisted of 4,046 patients (51% women). There were no significant gender differences in the use of thrombolysis, neuroimaging, carotid imaging, dysphagia screening, antithrombotic therapy, or neurology and other consultations. Women with ischemic stroke or TIA were less likely than men to be prescribed statins or undergo carotid imaging and endarterectomy within 6 months of stroke; women were more likely than men to receive antihypertensives. There were no significant gender differences in readmission or mortality rates after stroke. Interpretation: In this population-based study, we found little evidence of gender differences in stroke care or outcomes other than lipid-lowering therapy, carotid imaging, and endarterectomy. Further study is needed to assess the contribution of the provincial stroke strategy in eliminating gender differences in management of acute stroke and to better understand and target remaining gender differences in management. [Copyright &y& Elsevier]

Background: Direct enteral feeding tube (DET) placement for dysphagia after stroke is associated with poor outcomes. However, the relationship between timing of DET placement and poststroke mortality and disability is unknown. We sought to determine the risk of mortality and severe disability in patients who receive DET at different times after stroke.Methods: We used the Ontario Stroke Registry and linked administrative databases to identify patients with acute ischemic stroke or intracerebral hemorrhage between 2003 and 2013 who received DET (gastrostomy or jejunostomy) during their hospital admission. We grouped patients by week of DET placement and evaluated mortality at 30 days and 6 months after DET insertion, and disability at discharge. We used Cox proportional hazard models and multiple logistic regression to determine the association between time from admission to DET placement and outcomes, adjusting for patient and hospital factors.Results: In the study sample of 1367 patients, the median time from admission to DET placement was 17 days. After adjustment, each week of delay to DET placement was associated with lower mortality at 30 days (adjusted hazard ratio [aHR] .88, 95% confidence interval [CI] .79-.98), but not at 6 months (aHR .98, 95% CI .91- 1.05), and a higher likelihood of severe disability at discharge (adjusted odds ratio 1.35, 95% CI 1.13- 1.60).Conclusions: Later DET placement after stroke was associated with lower 30-day mortality but higher severe disability at discharge. Further research is needed to understand the reasons for these observations and to optimize patient selection and timing of DET. [ABSTRACT FROM AUTHOR]

Purpose: To compare hazard ratios obtained by using time on study (conventional) versus biological age as the time-scale in survival analyses for a known age-dependent association between an exposure and outcome.Methods: We conducted a retrospective cohort study of 9 million people in Ontario, Canada who were followed from 2003 to 2018 to identify incident ischemic stroke using linked administrative health data. Using cause-specific hazards models, we calculated hazard ratios (HR) of ischemic stroke in women compared to men using the two different time scales. By using piecewise estimates and interaction terms, we evaluate the effect of sex on stroke incidence across age groups.Results: In unadjusted analyses, the reduction in the hazard of ischemic stroke in women compared to men was greater with age as time-scale (HR 0.77; 0.76-0.78) compared to conventional time-scale (HR 0.93; 0.92-0.93); however, the estimates were similar (HR 0.78 with age vs. 0.77 with conventional) in multivariable adjusted analyses. The estimates obtained by two methods across different age groups varied modestly, except in those under 30 years (HR 1.47; 1.19-1.83 with age vs. 1.08; 0.99-1.17 with conventional).Conclusions: When evaluating age-dependent association between an exposure and outcome, estimates of association vary based on the time-scale used in survival analysis, requiring thoughtful consideration. [ABSTRACT FROM AUTHOR]

Background Among patients taking warfarin, lower socioeconomic status is associated with poorer control of anticoagulation. However, the extent to which socioeconomic status influences the risk of hemorrhage is unknown. We examined the extent to which socioeconomic status influences the risk of hemorrhage in older individuals newly commencing warfarin therapy for atrial fibrillation. Methods We conducted a population-based cohort study of individuals 66 years or older with atrial fibrillation who commenced warfarin therapy between April 1, 1997, and November 30th 2011, in Ontario, Canada. We used neighborhood-level income quintiles as a measure of socioeconomic status. The primary outcome was an emergency department visit or hospitalization for hemorrhage, and the secondary outcome was fatal hemorrhage. Results We studied 166,742 older patients with atrial fibrillation who commenced warfarin therapy. Of these, 16,371 (9.8%) were hospitalized for hemorrhage during a median follow-up of 369 (interquartile range 102-865) days. After multivariable adjustment using Cox proportional hazards regression, we found that those in the lowest-income quintile faced an increased risk of hospitalization for hemorrhage relative to those in the highest quintile (adjusted hazard ratio 1.18, 95% CI 1.12-1.23). Similarly, the risk of fatal hemorrhage (n = 1,802) was increased in the lowest-income relative to the highest-income quintile (adjusted hazard ratio 1.28, 95% CI 1.11-1.48). Conclusions Among older individuals receiving warfarin therapy for atrial fibrillation, lower socioeconomic status is a risk factor for hemorrhage and hemorrhage-related mortality. This factor should be carefully considered when initiating and monitoring warfarin therapy. [ABSTRACT FROM AUTHOR]

Background The clinical utility of routine transesophageal echocardiography (TEE) for patients with unexplained ischemic stroke is controversial. We performed a systematic review to determine the frequency of detection of new cardiac findings in patients with cryptogenic ischemic stroke (IS) undergoing transesophageal echocardiography (TEE). Methods Systematic review and meta-analysis of cohort studies of consecutive patients with “cryptogenic” IS undergoing TEE after routine etiologic workup. Patients were categorized into 2 groups: A (<55 years) and B (≥55 years). Outcomes included proportion of patients with new TEE-detected cardiac findings and proportion of patients commenced on oral anticoagulation after TEE. Results Twenty-seven studies were included (n = 5,653). We identified significant heterogeneity among studies and report a range of prevalence rates and I 2 statistic as our primary analysis. Prevalence of individual cardiac findings on TEE varied significantly among studies; patent foramen ovale (A: 12.0%-57.8%, I 2 = 89.9%; B: 3.9%-43.5%, I 2 = 86.7%), atrial septal aneurysm (A: 0-48.9%, I 2 = 91.9%; B: 3.5%-25.0%, I 2 = 84.5%), left atrial thrombus (A: 0-10.9%, I 2 = 61.1%; B: 0-21.2%, I 2 = 91.7%), spontaneous echo contrast (A: 0-11.9%, I 2 = 57.2%; B: 0-21.3%, I 2 = 89.8%), and aortic atheroma (A: 0-9.6%, I 2 = 53.8%; B: 2.8%-44.4%, I 2 = 89.7%). Definitions of common findings were not provided for many studies. Five studies (n = 591) reported on the proportion of patients who were commenced on anticoagulant therapy after TEE (range 0-30.7%). Conclusions Routine TEE in patients with cryptogenic IS identifies cardiac findings in a large proportion. However, there is marked interstudy variation in the definition and prevalence of common findings. Transesophageal echocardiography–detected findings prompted the introduction of anticoagulant therapy in up to one-third of patients. However, these were mostly not for established guideline-based indications based on randomized controlled trial evidence. It is unclear if routine use of TEE in patients with cryptogenic IS is indicated. [ABSTRACT FROM AUTHOR]

Abstract: This paper discusses the early lessons learned in establishing the Registry of the Canadian Stroke Network (RCSN), particularly the pitfalls related to the requirement for informed patient (or surrogate) consent for inclusion in the registry. The need for stroke registries to collect accurate data that are representative of all patients with acute stroke in a given community is emphasized, and how the current methodology strives to reach this goal is outlined. [Copyright &y& Elsevier]

Background: To evaluate the association between the proportion of life spent in a host nation and stroke incidence and outcomes among Canadian immigrants.Methods: We conducted a retrospective cohort study of 1.2 million adult Canadian immigrants (mean age 40 [±14.6] years, 50.5% women) who were followed between 2003 and 2018 using linked administrative health data. Using multivariable cause-specific hazard models, we evaluated the overall and sex-specific associations between the proportion of life spent in Canada (φ), modeled as restricted cubic splines, and ischemic stroke incidence and outcomes.Results: Compared to the median proportion of life in Canada (φ = 0.2), a J-shaped association between the proportion of life in Canada and ischemic stroke incidence and outcomes was observed. The adjusted hazard ratios of stroke incidence increased with both progressively lower and higher levels of φ [e.g., (HRφ =0.05 vs.φ = 0.20, 1.15; 1.09-1.21) and (HRφ = 0.50 vs. φ = 0.20, 1.45; 1.27-1.66)]. In sex-stratified analyses, the associations between φ and stroke incidence and outcomes were significant in men, but not in women.Conclusions: Stroke incidence and outcomes among immigrants varies with the proportion of life spent in Canada. Future work should identify factors driving the observed associations and the sex differences. [ABSTRACT FROM AUTHOR]

Previous research has established a relation between depression at the time of cardiac hospitalization and patient mortality. The objective of this study was to examine the role of depressive history and symptomatology during hospitalization on 5-year all-cause mortality after admission for an acute coronary syndrome. We recruited 750 patients who had unstable angina pectoris and myocardial infarction from 12 coronary care units between 1997 and 1999. Measurements included sociodemographic and clinic data and the Beck Depression Inventory (BDI). Data were linked to an administrative database to determine 5-year all-cause mortality. Survival data were adjusted using a Cox’s proportional hazards model. One hundred seventy-four participants (23.2%) self-reported a history of depressed mood for >2 weeks, 235 (31.3%) had elevated BDI scores at index hospitalization, with 105 (14.0%) reporting persistent depressive symptomatology. One hundred fifteen participants (15.3%) died by 5 years after hospitalization. After adjusting for prognostic indicators, such as cardiac disease severity, medical history, and smoking, depressive symptomatology during hospitalization was significantly predictive of mortality, but depressive history was not. Hazard ratios associated with BDI scores <10 versus those ≥10 at hospitalization ranged from 1.90 (95% confidence interval 1.12 to 3.24) at 2 years to 1.53 (95% confidence interval 1.04 to 2.24) at 5 years. In conclusion, the significance of depressive symptomatology at the time of, but not before, hospitalization underlines the need for early identification of increased distress and renews calls to identify treatments that not only improve quality of life but also decrease the risk of mortality. [Copyright &y& Elsevier]

Background Little is known about stroke care and outcomes in those residing in rural compared to urban areas. Methods We conducted a cohort study on a population-based sample of patients with stroke or transient ischemic attack seen at 153 acute care hospitals in the province of Ontario, Canada, between April 1, 2008 and March 31, 2011. Based on their primary residence, patients were categorized as residing in a rural (population < 10,000), medium urban (population 10,000–99,999) or large urban (population ≥ 100,000) area. In the study sample of 15,713, we compared processes of stroke care (use of thrombolysis, stroke unit care, investigations, consultations and treatments) and outcomes (30-day mortality, disability at discharge) in those from rural and urban areas, with multivariable models constructed to evaluate the association between rural residence and outcomes after adjustment for potential confounders. Results Patients from rural areas were less likely than those from urban areas to receive stroke unit care, brain imaging within 24 h, carotid imaging, and consultations from neurologists, physiotherapists, occupational therapists and speech language pathologists, and were less likely to be transferred to inpatient rehabilitation facilities. Use of antithrombotic agents and lipid lowering therapy was similar in rural and urban residents, as was disability at discharge. There was a trend toward higher 30-day mortality in rural compared to urban residents (adjusted hazard ratio 1.14; 95% confidence interval 0.99–1.32). Conclusion Rural residence is associated with lower use of key stroke care interventions after stroke. Future work should focus on developing interventions to address gaps in stroke care in rural areas. [ABSTRACT FROM AUTHOR]

Summary: Background: Exemestane can prevent breast cancer in postmenopausal women. Because of potential widespread use, we examined the safety of exemestane on bone health. Methods: In this nested safety substudy of the MAP.3 trial (a randomised, placebo-controlled, double-blind trial of exemestane 25 mg a day for the primary prevention of breast cancer), we included postmenopausal women from five centres who were eligible to participate in MAP.3, not osteoporotic, not receiving drugs for bone-related disorders, with baseline lumbar spine, total hip, and femoral neck T-scores above −2·0. The primary endpoint was percent change from baseline to 2 years in total volumetric bone mineral density (BMD) at the distal radius by high-resolution peripheral quantitative CT. The primary analysis was per protocol using a non-inferiority margin. This analysis was done earlier than originally planned because of the impending announcement of MAP.3 results and subsequent unmasking of patients to treatment assignment. This study is registered with ClinicalTrials.gov, number NCT01144468, and has been extended to 5 years of unmasked follow-up. Findings: 351 women (176 given exemestane, 175 given placebo; median age 61·3 years [IQR 59·2–64·9]) met our inclusion criteria and completed baseline assessment. At the time of clinical cutoff, 242 women had completed 2-year follow-up (124 given exemestane, 118 given placebo). From baseline to 2 years, the mean percent change in total volumetric BMD at the distal radius was −6·1% (95% CI −7·0 to −5·2) in the exemestane group and −1·8% (−2·4 to −1·2) in the placebo group (difference −4·3%, 95% CI −5·3 to −3·2; p<0·0001). The lower limit of the 95% CI was lower than our non-inferiority margin of negative 4% (one-sided test for non-inferiority p=0·70), meaning the hypothesis that exemestane was inferior could not be rejected. At the distal tibia, the mean percent change in total volumetric BMD from baseline to 2 years was −5·0% (95% CI −5·5 to −4·4) in the exemestane group and −1·3% (−1·7 to −1·0) in the placebo group (difference −3·7%, 95% CI −4·3 to −3·0; p<0·0001). The mean percent change in cortical thickness was −7·9% (SD 7·3) in the exemestane group and −1·1% (5·7) in the placebo group at the distal radius (difference −6·8%, 95% CI −8·5 to −5·0; p<0·0001) and −7·6% (SD 5·9) in the exemestane group and −0·7% (4·9) in the placebo group at the distal tibia (difference −6·9%, −8·4 to −5·5; p<0·0001). Decline in areal BMD, as measured by dual-energy x-ray absorptiometry, in the exemestane group compared with the placebo group occurred at the lumbar spine (−2·4% [95% CI −3·1 to −1·7] exemestane vs −0·5% [−1·1 to 0·2] placebo; difference −1·9%, 95% CI −2·9 to −1·0; p<0·0001), total hip (−1·8% [−2·3 to −1·2] exemestane vs −0·6% [−1·1 to −0·1] placebo; difference −1·2%, −1·9 to −0·4; p=0·004), and femoral neck (−2·4% [−3·2 to −1·7] exemestane vs −0·8% [−1·5 to 0·1] placebo; difference −1·6%, −2·7 to −0·6; p=0·002). Interpretation: 2 years of treatment with exemestane worsens age-related bone loss in postmenopausal women despite calcium and vitamin D supplementation. Women considering exemestane for the primary prevention of breast cancer should weigh their individual risks and benefits. For women taking exemestane, regular bone monitoring plus adequate calcium and vitamin D supplementation are important. To assess the effect of our findings on fracture risk, long-term follow-up is needed. Funding: Canadian Breast Cancer Research Alliance (Canadian Institutes of Health Research/Canadian Cancer Society). [Copyright &y& Elsevier]