Trial of an Intervention to Improve Acute Heart Failure Outcomes.

BACKGROUND: Patients with acute heart failure are frequently or systematically hospitalized, often because the risk of adverse events is uncertain and the options for rapid follow-up are inadequate. Whether the use of a strategy to support clinicians in making decisions about discharging or admitting patients, coupled with rapid follow-up in an outpatient clinic, would affect outcomes remains uncertain. METHODS: In a stepped-wedge, cluster-randomized trial conducted in Ontario, Canada, we randomly assigned 10 hospitals to staggered start dates for one-way crossover from the control phase (usual care) to the intervention phase, which involved the use of a point-of-care algorithm to stratify patients with acute heart failure according to the risk of death. During the intervention phase, low-risk patients were discharged early (in ≤3 days) and received standardized outpatient care, and high-risk patients were admitted to the hospital. The coprimary outcomes were a composite of death from any cause or hospitalization for cardiovascular causes within 30 days after presentation and the composite outcome within 20 months. RESULTS: A total of 5452 patients were enrolled in the trial (2972 during the control phase and 2480 during the intervention phase). Within 30 days, death from any cause or hospitalization for cardiovascular causes occurred in 301 patients (12.1%) who were enrolled during the intervention phase and in 430 patients (14.5%) who were enrolled during the control phase (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.78 to 0.99; P = 0.04). Within 20 months, the cumulative incidence of primary-outcome events was 54.4% (95% CI, 48.6 to 59.9) among patients who were enrolled during the intervention phase and 56.2% (95% CI, 54.2 to 58.1) among patients who were enrolled during the control phase (adjusted hazard ratio, 0.95; 95% CI, 0.92 to 0.99). Fewer than six deaths or hospitalizations for any cause occurred in low- or intermediate-risk patients before the first outpatient visit within 30 days after discharge. CONCLUSIONS: Among patients with acute heart failure who were seeking emergency care, the use of a hospital-based strategy to support clinical decision making and rapid follow-up led to a lower risk of the composite of death from any cause or hospitalization for cardiovascular causes within 30 days than usual care. (Funded by the Ontario SPOR Support Unit and others; COACH ClinicalTrials.gov number, NCT02674438.).

Stroke risk in women with atrial fibrillation.

BACKGROUND AND AIMS: Female sex is associated with higher rates of stroke in atrial fibrillation (AF) after adjustment for other CHA2DS2-VASc factors. This study aimed to describe sex differences in age and cardiovascular care to examine their relationship with stroke hazard in AF. METHODS: Population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. Cause-specific hazard regression was used to estimate the adjusted hazard ratio (HR) for stroke associated with female sex over a 2-year follow-up. Model 1 included CHA2DS2-VASc factors, with age modelled as 66-74 vs. ≥ 75 years. Model 2 treated age as a continuous variable and included an age-sex interaction term. Model 3 further accounted for multimorbidity and markers of cardiovascular care. RESULTS: The cohort consisted of 354 254 individuals with AF (median age 78 years, 49.2% female). Females were more likely to be diagnosed in emergency departments and less likely to receive cardiologist assessments, statins, or LDL-C testing, with higher LDL-C levels among females than males. In Model 1, the adjusted HR for stroke associated with female sex was 1.27 (95% confidence interval 1.21-1.32). Model 2 revealed a significant age-sex interaction, such that female sex was only associated with increased stroke hazard at age >70 years. Adjusting for markers of cardiovascular care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years. CONCLUSION: Older age and inequities in cardiovascular care may partly explain higher stroke rates in females with AF.

Seasonal Variations in Stroke Occurrence.

BACKGROUND: Understanding seasonal variations in stroke can help stakeholders identify underlying causes in seasonal trends, and tailor resources appropriately to times of highest needs. We sought to evaluate the seasonal occurrence of stroke and its subtypes. METHODS: We conducted a retrospective cohort study using administrative data from January 1st, 2003, to December 31st, 2017, in Ontario, Canada's most populous province. We evaluated seasonal variations in stroke occurrence by subtype, via age/sex standardized rates and adjusted rate ratios using Poisson regressions. In those with stroke, we evaluated 30-day case fatality risks by season, adjusted for age, sex, stroke type, and comorbid conditions, and then used Cox proportional hazard models to estimate the effect of season on the fatality. The administrative data used in this study were from the Canadian Institute for Health Information's Discharge Abstract Database, the National Ambulatory Care Reporting System Database, the Ontario Registered Persons Database, and the 2006 and 2011 Canada Census and linked administrative databases. RESULTS: During our study period, we observed 394,145 strokes or TIA events, with a decrease in monthly hospitalization/emergency department visits per 100,000 people between January 2003 and December 2017 from 24.22 to 17.43. Compared to the summer, overall stroke occurrence was similar in the spring but slightly lower in the fall (adjusted rate ratio [aRR] 0.97, 95% confidence interval [CI] 0.96-0.98) and winter (aRR 0.94, 95% CI: 0.94-0.95). There were minor variations by stroke subtype. Winter was associated with the highest risk of stroke case fatality compared to the summer (12.4% vs. 11.4%, adjusted hazard ratio 1.10, 95% CI: 1.07-1.13). CONCLUSIONS: We found seasonal variations in stroke occurrence and case fatality, although the absolute differences were small. Further work is needed to better understand how environmental or meteorological factors might affect stroke risk.

Trajectories of P2Y12 inhibitor adherence in patients with acute coronary syndromes.

PURPOSE: P2Y12 inhibitors (P2Y12i) reduce cardiac events after acute coronary syndromes (ACS). However, suboptimal P2Y12i adherence persists. We aimed to examine P2Y12i non-adherence using group-based trajectory methods and to identify adherence predictors. METHODS: We conducted a population-based, retrospective cohort study using administrative data in Ontario, Canada of patients ≥65 years admitted for ACS between April 2014 and March 2018 with a P2Y12i dispensed within 7 days of discharge. We used group-based trajectory models to characterize longitudinal 1-year adherence patterns. Predictors associated with each adherence trajectory were identified by multinomial logistic regression. RESULTS: We included 11 917 patients using clopidogrel and 9763 using ticagrelor, aged [mean ± SD]: 77.33 ± 8.31/73.59 ± 6.79 years; men: 56.2%/65.4%, respectively. We identified 3 longitudinal adherence trajectories, that differed by agent: 75% of clopidogrel and 68% of ticagrelor patients showed a consistently adherent trajectory, while 13%/17% were gradually, and 12%/15% were rapidly non-adherent, respectively (p < 0.001). Differing baseline characteristics in each cohort were associated with observed adherence trajectories. Concomitant atrial fibrillation and prior bleeding history were associated with non-adherence among clopidogrel users. Among ticagrelor users, women and older persons were more likely to be rapidly non-adherent, adherence declining steeply starting 1 month post-ACS. CONCLUSIONS: We identified distinct adherence trajectories for clopidogrel and ticagrelor post-ACS, with 3 out of 4 clopidogrel patients but only 2 out of 3 ticagrelor patients in the consistently adherent trajectory. Intensive interventions targeted to the period of steep adherence decline post-ACS, particularly for women and older persons initiating ticagrelor, and patients with atrial fibrillation on clopidogrel should be considered and investigated further.

Validation of the Passive Surveillance Stroke Severity Score in Three Canadian Provinces.

BACKGROUND: Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada. METHODS: We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models' discriminative values using Uno's c-statistic, comparing models with versus without PaSSV. RESULTS: We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable. CONCLUSION: PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.

Association of Neighborhood-Level Material Deprivation With Atrial Fibrillation Care in a Single-Payer Health Care System: A Population-Based Cohort Study.

BACKGROUND: There are limited data on the association of material deprivation with clinical care and outcomes after atrial fibrillation (AF) diagnosis in jurisdictions with universal health care. METHODS: This was a population-based cohort study of individuals ≥66 years of age with first diagnosis of AF between April 1, 2007, and March 31, 2019, in the Canadian province of Ontario, which provides public funding and prohibits private payment for medically necessary physician and hospital services. Prescription medications are subsidized for residents >65 years of age. The primary exposure was neighborhood material deprivation, a metric derived from Canadian census data to estimate inability to attain basic material needs. Neighborhoods were categorized by quintile from Q1 (least deprived) to Q5 (most deprived). Cause-specific hazards regression was used to study the association of material deprivation quintile with time to AF-related adverse events (death or hospitalization for stroke, heart failure, or bleeding), clinical services (physician visits, cardiac diagnostics), and interventions (anticoagulation, cardioversion, ablation) while adjusting for individual characteristics and regional cardiologist supply. RESULTS: Among 347 632 individuals with AF (median age 79 years, 48.9% female), individuals in the most deprived neighborhoods (Q5) had higher prevalence of cardiovascular disease, risk factors, and noncardiovascular comorbidity relative to residents of the least deprived neighborhoods (Q1). After adjustment, Q5 residents had higher hazards of death (hazard ratio [HR], 1.16 [95% CI, 1.13-1.20]) and hospitalization for stroke (HR, 1.16 [95% CI, 1.07-1.27]), heart failure (HR, 1.14 [95% CI, 1.11-1.18]), or bleeding (HR, 1.16 [95% CI, 1.07-1.25]) relative to Q1. There were small differences across quintiles in primary care physician visits (HR, Q5 versus Q1, 0.91 [95% CI, 0.89-0.92]), echocardiography (HR, Q5 versus Q1, 0.97 [95% CI, 0.96-0.99]), and dispensation of anticoagulation (HR, Q5 versus Q1, 0.97 [95% CI, 0.95-0.98]). There were more prominent disparities for Q5 versus Q1 in cardiologist visits (HR, 0.84 [95% CI, 0.82-0.86]), cardioversion (HR, 0.80 [95% CI, 0.76-0.84]), and ablation (HR, 0.45 [95% CI, 0.30-0.67]). CONCLUSIONS: Despite universal health care and prescription medication coverage, residents of more deprived neighborhoods were less likely to visit cardiologists or receive rhythm control interventions after AF diagnosis, even though they exhibited higher cardiovascular disease burden and higher risk of adverse outcomes.

Attributable Costs of Stroke in Ontario, Canada and Their Variation by Stroke Type and Social Determinants of Health.

BACKGROUND: Estimates of attributable costs of stroke are scarce, as most prior studies do not account for the baseline health care costs in people at risk of stroke. We estimated the attributable costs of stroke in a universal health care setting and their variation across stroke types and several social determinants of health. METHODS: We undertook a population-based administrative database-derived matched retrospective cohort study in Ontario, Canada. Community-dwelling adults aged ≥40 years with a stroke between 2003 and 2018 were matched (1:1) on demographics and comorbidities with controls without stroke. Using a difference-in-differences approach, we estimated the mean 1-year direct health care costs attributable to stroke from a public health care payer perspective, accounting for censoring with a weighted available sample estimator. We described health sector-specific costs and reported variation across stroke type and social determinants of health. RESULTS: The mean 1-year attributable costs of stroke were Canadian dollars 33 522 (95% CI, $33 231-$33 813), with higher costs for intracerebral hemorrhage ($40 244; $39 193-$41 294) than ischemic stroke ($32 547; $32 252-$32 843). Most of these costs were incurred in acute care hospitals ($15 693) and rehabilitation facilities ($7215). Compared with all patients with stroke, the mean attributable costs were higher among immigrants ($40 554; $39 316-$41 793), those aged <65 years ($35 175; $34 533-$35 818), and those residing in low-income neighborhoods ($34 687; $34 054-$35 320) and lower among rural residents ($29 047; $28 362-$29 731). CONCLUSIONS: Our findings of high attributable costs of stroke, especially in immigrants, younger patients, and residents of low-income neighborhoods, can be used to evaluate potential health care cost savings associated with different primary stroke prevention strategies.

Maternal Health Outcomes After Pregnancy-Associated Stroke: A Population-Based Study With 19 Years of Follow-Up.

BACKGROUND: Pregnancy-associated stroke carries high short-term morbidity and mortality, but data on subsequent maternal outcomes are limited. We evaluated long-term maternal health outcomes after pregnancy-associated stroke. METHODS: In this retrospective cohort study, we used administrative data to identify pregnant adults aged ≤49 years with stroke between 2002-2020 in Ontario, Canada and 2 comparison groups: (1) non-pregnant female patients with stroke and (2) pregnant patients without stroke. Patients who survived the index admission were followed until 2021. After propensity score matching, we used Cox regression with a robust variance estimator to compare pregnant patients with stroke and the 2 comparison groups for the composite outcome of death and all-cause non-pregnancy readmission. Where proportional hazard assumption was not met, we reported time-varying hazard ratios (HR) with 95% CIs by modeling the log-hazard ratio as a function of time using restricted cubic splines. RESULTS: We identified 217 pregnant patients with stroke, 7604 non-pregnant patients with stroke, and 1 496 256 pregnant patients without stroke. Of the 202 pregnant patients with stroke who survived the index stroke admission, 41.6% (6.8 per 100 person-years) subsequently died or were readmitted during follow-up. Median follow-up times were 5 years (pregnancy-associated stroke), 3 years (non-pregnant stroke), and 8 years (pregnant without stroke). Pregnant patients with stroke had a lower hazard of death and all-cause readmission compared with non-pregnant patients with stroke at 1-year follow-up (HR, 0.64 [95% CI, 0.44-0.94]), but this association did not persist during longer-term follow-up. Conversely, pregnant patients with stroke had higher hazard of death and readmission compared with pregnant patients without stroke at 1-year follow-up (HR, 5.70 [95% CI, 3.04-10.66]), and this association persisted for a decade. CONCLUSIONS: Stroke during pregnancy is associated with long-term health consequences. It is essential to transition care postpartum to primary or specialty care to optimize vascular health.

Association of prior outpatient diabetes screening with cardiovascular events and mortality among people with incident diabetes: a population-based cohort study.

BACKGROUND: Outcomes of diabetes screening in contemporary, multi-ethnic populations are unknown. We examined the association of prior outpatient diabetes screening with the risks of cardiovascular events and mortality in Ontario, Canada. METHODS: We conducted a population-based cohort study using administrative databases among adults aged ≥ 20 years with incident diabetes diagnosed during 2014-2016. The exposure was outpatient diabetes screening performed within 3 years prior to diabetes diagnosis. The co-primary outcomes were (1) a composite of all-cause mortality and hospitalization for myocardial infarction, stroke, coronary revascularization, and (2) all-cause mortality (followed up until 2018). We calculated standardized rates of each outcome and conducted cause-specific hazard modelling to determine the adjusted hazard ratio (HR) of the outcomes, adjusting for prespecified confounders and accounting for the competing risk of death. RESULTS: We included 178,753 Ontarians with incident diabetes (70.2% previously screened). Individuals receiving prior screening were older (58.3 versus 53.4 years) and more likely to be women (49.6% versus 40.0%) than previously unscreened individuals. Individuals receiving prior screening had relatively lower standardized event rates than those without prior screening across all outcomes (composite: 12.8 versus 18.1, mortality: 8.2 versus 11.1 per 1000 patient-years). After multivariable adjustment, prior screening was associated with 34% and 32% lower risks of the composite (HR 0.66, 0.63-0.69) and mortality (0.68, 0.64-0.72) outcomes. Among those receiving prior screening, a result in the prediabetes range was associated with lower risks of the composite (0.82, 0.77-0.88) and mortality (0.71, 0.66-0.78) outcomes than a result in the normoglycemic range. CONCLUSIONS: Previously screened individuals with diabetes had lower risks of cardiovascular events and mortality versus previously unscreened individuals. Better risk assessment tools are needed to support wider and more appropriate uptake of diabetes screening, especially among young adults.

Change in Hospital Risk-standardized Stroke Mortality Performance With and Without the Passive Surveillance Stroke Severity Score.

BACKGROUND: Adjustment for baseline stroke severity is necessary for accurate assessment of hospital performance. We evaluated whether adjusting for the Passive Surveillance Stroke SeVerity (PaSSV) score, a measure of stroke severity derived using administrative data, changed hospital-specific estimated 30-day risk-standardized mortality rate (RSMR) after stroke. METHODS: We used linked administrative data to identify adults who were hospitalized with ischemic stroke or intracerebral hemorrhage across 157 hospitals in Ontario, Canada between 2014 and 2019. We fitted a random effects logistic regression model using Markov Chain Monte Carlo methods to estimate hospital-specific 30-day RSMR and 95% credible intervals with adjustment for age, sex, Charlson comorbidity index, and stroke type. In a separate model, we additionally adjusted for stroke severity using PaSSV. Hospitals were defined as low-performing, average-performing, or high-performing depending on whether the RSMR and 95% credible interval were above, overlapping, or below the cohort's crude mortality rate. RESULTS: We identified 65,082 patients [48.0% were female, the median age (25th,75th percentiles) was 76 years (65,84), and 86.4% had an ischemic stroke]. The crude 30-day all-cause mortality rate was 14.1%. The inclusion of PaSSV in the model reclassified 18.5% (n=29) of the hospitals. Of the 143 hospitals initially classified as average-performing, after adjustment for PaSSV, 20 were reclassified as high-performing and 8 were reclassified as low-performing. Of the 4 hospitals initially classified as low-performing, 1 was reclassified as high-performing. All 10 hospitals initially classified as high-performing remained unchanged. CONCLUSION: PaSSV may be useful for risk-adjusting mortality when comparing hospital performance. External validation of our findings in other jurisdictions is needed.

Performance of administrative database frailty instruments in predicting clinical outcomes and cost for patients undergoing transcatheter aortic valve implantation: a historical cohort study.

PURPOSE: Frailty instruments may improve prognostic estimates for patients undergoing transcatheter aortic valve implantation (TAVI). Few studies have evaluated and compared the performance of administrative database frailty instruments for patients undergoing TAVI. This study aimed to examine the performance of administrative database frailty instruments in predicting clinical outcomes and costs in patients who underwent TAVI. METHODS: We conducted a historical cohort study of 3,848 patients aged 66 yr or older who underwent a TAVI procedure in Ontario, Canada from 1 April 2012 to 31 March 2018. We used the Johns Hopkins Adjusted Clinical Group (ACG) frailty indicator and the Hospital Frailty Risk Score (HFRS) to assign frailty status. Outcomes of interest were in-hospital mortality, one-year mortality, rehospitalization, and healthcare costs. We compared the performance of the two frailty instruments with that of a reference model that adjusted baseline covariates and procedural characteristics. Accuracy measures included c-statistics, Akaike information criterion (AIC), Bayesian information criterion (BIC), integrated discrimination improvement (IDI), net reclassification index (NRI), bias, and accuracy of cost estimates. RESULTS: A total of 863 patients (22.4%) were identified as frail using the Johns Hopkins ACG frailty indicator and 865 (22.5%) were identified as frail using the HFRS. Although agreement between the frailty instruments was fair (Kappa statistic = 0.322), each instrument classified different subgroups as frail. Both the Johns Hopkins ACG frailty indicator (rate ratio [RR], 1.13; 95% confidence interval [CI], 1.06 to 1.20) and the HFRS (RR, 1.14; 95% CI, 1.07 to 1.21) were significantly associated with increased one-year costs. Compared with the reference model, both the Johns Hopkins ACG frailty indicator and HFRS significantly improved NRI for one-year mortality (Johns Hopkins ACG frailty indicator: NRI, 0.160; P < 0.001; HFRS: NRI, 0.146; P = 0.001) and rehospitalization (Johns Hopkins ACG frailty indicator: NRI, 0.201; P < 0.001; HFRS: NRI, 0.141; P = 0.001). These improvements in NRI largely resulted from classification improvement among those who did not experience the event. With one-year mortality, there was a significant improvement in IDI (IDI, 0.003; P < 0.001) with the Johns Hopkins ACG frailty indicator. This improvement in performance resulted from an increase in the mean probability of the event among those with the event. CONCLUSION: Preoperative frailty assessment may add some predictive value for TAVI outcomes. Use of administrative database frailty instruments may provide small but significant improvements in case-mix adjustment when profiling hospitals for certain outcomes.

RéSUMé: OBJECTIF: L'utilisation d'indicateur de fragilité pourrait améliorer l'évaluation pronostique des patients bénéficiant d'un remplacement valvulaire aortique par voie percutanée (procédure TAVI). Peu d'études ont évalué et comparé la performance des instruments d'évaluation de la fragilité développés à partir de données administratives chez les patients bénéficiant d'un TAVI. Nous avions pour objectif d'examiner la performance des instruments d'évaluation de la fragilité développés à partir de données administratives dans la prédiction des issues cliniques et des coûts chez les patients ayant bénéficié d'un TAVI. MéTHODE: Nous avons réalisé une étude de cohorte historique auprès de 3848 patients âgés de 66 ans ou plus qui ont bénéficié d'une procédure TAVI en Ontario, Canada, du 1er avril 2012 au 31 mars 2018. Nous avons utilisé l'indicateur de fragilité ACG (Adjusted Clinical Group) de Johns Hopkins et le score de risque de fragilité à l'hôpital (HFRS) pour définir la fragilité. Les critères d'évaluation étaient la mortalité hospitalière, la mortalité à un an, la réhospitalisation et les coûts des soins de santé. Nous avons comparé la performance des deux instruments d'évaluation de la fragilité à celle d'un modèle de référence qui ajustait les covariables de base et les caractéristiques procédurales. Les mesures d'exactitude comprenaient l'analyse statistique c, le critère d'information d'Akaike (AIC), le critère d'information bayésien (BIC), l'amélioration de la discrimination intégrée (IDI), l'indice NRI (net reclassification index), le biais et l'exactitude des estimations de coûts. RéSULTATS: Au total, 863 patients (22,4 %) ont été identifiés comme fragiles à l'aide de l'indicateur de fragilité ACG de Johns Hopkins, et 865 (22,5 %) ont été identifiés comme fragiles à l'aide du HFRS. Bien que l'agrément entre les instruments d'évaluation de la fragilité ait été acceptable (statistique de Kappa = 0,322), chaque instrument a classé des sous-groupes différents comme étant fragiles. L'indicateur de fragilité ACG de Johns Hopkins (rapport de taux [RR], 1,13; intervalle de confiance à 95 % [IC], 1,06 à 1,20) et le HFRS (RR, 1,14; IC 95 %, 1,07 à 1,21) étaient associés de façon significative à une augmentation des coûts sur un an. Par rapport au modèle de référence, l'indicateur de fragilité ACG de Johns Hopkins améliorent de façon significative le NRI pour la mortalité (l'indicateur de fragilité ACG de Johns Hopkins: NRI, 0.160; P < 0.001; HFRS: NRI, 0.146; P = 0.001) et la réhospitalisation (l'indicateur de fragilité ACG: NRI, 0.201; P < 0.001; HFRS: NRI, 0.141; P = 0.001) à un an. Ces améliorations du NRI résultent en grande partie de l'amélioration de la classification chez ceux qui n'ont pas bénéficié d'un TAVI. En ce qui a trait à la mortalité à un an, il y a eu une amélioration significative de l'IDI (IDI, 0,003; P < 0,001) avec l'indicateur de fragilité ACG de Johns Hopkins. Cette amélioration de la performance résultait d'une augmentation de la probabilité moyenne de TAVI chez les personnes ayant vécu l'événement. CONCLUSION: L'évaluation préopératoire de la fragilité peut ajouter une certaine valeur prédictive aux issues cliniques suivant une procédure de TAVI. L'utilisation d'instruments d'évaluation de la fragilité développés à partir de données administratives peut apporter des améliorations mineures mais significatives pour l'ajustement de risque lors de l'évaluation des hôpitaux en fonction de certaines issues cliniques.

Intravenous Thrombolysis After First-Ever Ischemic Stroke and Reduced Incident Dementia Rate.

BACKGROUND: The use of intravenous thrombolysis is associated with improved clinical outcomes. Whether thrombolysis is associated with reduced incidence of poststroke dementia remains uncertain. We sought to estimate if the use of thrombolysis following first-ever ischemic stroke was associated with a reduced rate of incident dementia using a pragmatic observational design. METHODS: We included first-ever ischemic stroke patients from the Ontario Stroke Registry who had not previously been diagnosed with dementia. The primary outcome was incident dementia ascertained by a validated diagnostic algorithm. We employed inverse probability of treatment-weighted Cox proportional hazard models to estimate the cause-specific hazard ratio for the association of thrombolysis and incident dementia at 1 and 5 years following stroke. RESULTS: From July 2003 to March 2013, 7072 patients with ischemic stroke were included, 3276 (46.3%) were female and mean age was 71.0 (SD, 12.8) years. Overall, 38.2% of the cohort (n=2705) received thrombolysis, 77.2% (n=2087) of which was administered within 3 hours of stroke onset. In the first year following stroke, thrombolysis administration was associated with a 24% relative reduction in the rate of developing dementia (cause-specific hazard ratio, 0.76 [95% CI, 0.58-0.97]). This association remained significant at 5 years (cause-specific hazard ratio, 0.79 [95% CI, 0.66-0.91]) and at the end of follow-up (median 6.3 years; cause-specific hazard ratio, 0.79 [95% CI, 0.68-0.89]). CONCLUSIONS: Thrombolysis administration following first-ever ischemic stroke was independently associated with a reduced rate of dementia. Incident dementia should be considered as a relevant outcome when evaluating risk/benefit of thrombolysis in ischemic stroke patients.

Using fractional polynomials and restricted cubic splines to model non-proportional hazards or time-varying covariate effects in the Cox regression model.

The Cox proportional hazards model is used extensively in clinical and epidemiological research. A key assumption of this model is that of proportional hazards. A variable satisfies the proportional hazards assumption if the effect of that variable on the hazard function is constant over time. When the proportional hazards assumption is violated for a given variable, a common approach is to modify the model so that the regression coefficient associated with the given variable is assumed to be a linear function of time (or of log-time), rather than being constant or fixed. However, this is an unnecessarily restrictive assumption. We describe two different methods to allow a regression coefficient, and thus the hazard ratio, in a Cox model to vary as a flexible function of time. These methods use either fractional polynomials or restricted cubic splines to model the log-hazard ratio as a function of time. We illustrate the utility of these methods using data on 12 705 patients who presented to a hospital emergency department with a primary diagnosis of heart failure. We used a Cox model to assess the association between elevated cardiac troponin at presentation and the hazard of death after adjustment for an extensive set of covariates. SAS code for implementing the restricted cubic spline approach is provided, while an existing Stata function allows for the use of fractional polynomials.

Post-acute health care burden after SARS-CoV-2 infection: a retrospective cohort study.

BACKGROUND: The post-acute burden of health care use after SARS-CoV-2 infection is unknown. We sought to quantify the post-acute burden of health care use after SARS-CoV-2 infection among community-dwelling adults in Ontario by comparing those with positive and negative polymerase chain reaction (PCR) test results for SARS-CoV-2 infection. METHODS: We conducted a retrospective cohort study involving community-dwelling adults in Ontario who had a PCR test between Jan. 1, 2020, and Mar. 31, 2021. Follow-up began 56 days after PCR testing. We matched people 1:1 on a comprehensive propensity score. We compared per-person-year rates for health care encounters at the mean and 99th percentiles, and compared counts using negative binomial models, stratified by sex. RESULTS: Among 531 702 matched people, mean age was 44 (standard deviation [SD] 17) years and 51% were female. Females who tested positive for SARS-CoV-2 had a mean of 1.98 (95% CI 1.63 to 2.29) more health care encounters overall per-person-year than those who had a negative test result, with 0.31 (95% CI 0.05 to 0.56) more home care encounters to 0.81 (95% CI 0.69 to 0.93) more long-term care days. At the 99th percentile per-person-year, females who tested positive had 6.48 more days of hospital admission and 28.37 more home care encounters. Males who tested positive for SARS-CoV-2 had 0.66 (95% CI 0.34 to 0.99) more overall health care encounters per-person-year than those who tested negative, with 0.14 (95% CI 0.06 to 0.21) more outpatient encounters and 0.48 (95% CI 0.36 to 0.60) long-term care days, and 0.43 (95% CI -0.67 to -0.21) fewer home care encounters. At the 99th percentile, they had 8.69 more days in hospital per-person-year, with fewer home care (-27.31) and outpatient (-0.87) encounters. INTERPRETATION: We found significantly higher rates of health care use after a positive SARS-CoV-2 PCR test in an analysis that matched test-positive with test-negative people. Stakeholders can use these findings to prepare for health care demand associated with post-COVID-19 condition (long COVID).

Patient clustering in primary care settings: Outcomes and quality of care.

OBJECTIVE: To determine whether neighbours who share the same family physicians have better cardiovascular and health care outcomes. DESIGN: Retrospective cohort study using administrative health databases. SETTING: Ontario. PARTICIPANTS: The study population included 2,690,482 adult patients cared for by 1710 family physicians. INTERVENTIONS: Adult residents of Ontario were linked to their family physicians and the geographic distance between patients in the same panel or list was calculated. Using distance between patients within a panel to stratify physicians into quintiles of panel proximity, physicians and patients from close-proximity practices were compared with those from more-distant-proximity practices. Age- and sex-standardized incidence rates and hazard ratios from cause-specific hazards regression models were determined. MAIN OUTCOME MEASURES: The occurrence of a major cardiovascular event during a 5-year follow-up period (2008 to 2012). RESULTS: Patients of panels in the closest-proximity quintile lived an average of 3.9 km from the 10 closest patients in their panel compared with 12.4 km for the 10 closest patients of panels in the distant-proximity quintile. After adjusting for various patient and physician characteristics, patients in the most-distant-proximity practices had a 24% higher rate of cardiovascular events (adjusted hazard ratio=1.24 [95% CI 1.20 to 1.28], P<.001) than patients in the closest-proximity practices. Age- and sex-standardized all-cause mortality and total per patient health care costs were also lowest in the closest-proximity quintile. In sensitivity analyses restricted to large urban communities and to White long-term residents, results were similar. CONCLUSION: The better cardiovascular outcomes observed in close-proximity panels may be related to a previously unrecognized mechanism of social connectedness that extends the effectiveness of primary care practitioners.

Stroke Incidence by Sex Across the Lifespan.

BACKGROUND AND PURPOSE: We evaluated the influence of age on the association between sex and the incidence of stroke or transient ischemic attack (TIA) using a population-based cohort from Ontario, Canada. METHODS: We followed a cohort of adults (≥18 years) without prior stroke from January 1, 2003 (cohort start date) to March 31, 2018, to identify incident events. We calculated hazard ratios (HRs), in women compared to men, of incident stroke or TIA, adjusted for demographics and comorbidities, overall and stratified by stroke type. We calculated piecewise adjusted HRs for each decade of age to evaluate the effect of age on sex differences in stroke incidence. RESULTS: We followed 9.2 million adults for a median of 15 years and observed 280,197 incident stroke or TIA events. Compared with men, women had an overall lower adjusted hazard of stroke or TIA (HR, 0.82 [95% CI, 0.82-0.83]), with similar findings across all stroke types except for subarachnoid hemorrhage (HR, 1.29 [95% CI, 1.24-1.33]). We found a U-shaped association between age and sex differences in the incidence of stroke or TIA: compared with men, the hazard of stroke was higher in women among those aged ≤30 years (HR, 1.26 [95% CI, 1.10-1.45]), lower among those between ages 40 and 80 years (eg, age 50-59, HR, 0.69 [95% CI, 0.68-0.70]), and similar among those aged ≥80 years (HR, 0.99 [95% CI, 0.98-1.01]). CONCLUSIONS: Overall, women have a lower hazard of stroke than men, but this association varies by age and across stroke types. Recognition of age-sex variations in stroke incidence can help guide prevention efforts to reduce stroke incidence in both men and women.

Rationale and design of the comparison of outcomes and access to care for heart failure (COACH) trial: A stepped wedge cluster randomized trial.

BACKGROUND: Heart failure (HF) is an ambulatory care sensitive condition and a leading reason for emergency department (ED) visits and hospitalizations. Improved decision-making and care may enhance safety and efficiency for patients presenting to the ED with acute HF. OBJECTIVES: We will evaluate an intervention comprised of 2 complementary components: (1) the Emergency Heart Failure Mortality Risk Grade simultaneous 7- and 30-day (EHMRG30-ST) risk scores, which will inform admission-discharge decisions, and (2) a rapid outpatient follow-up (RAPID-HF) clinic for low-to-intermediate risk patients on cardiovascular readmissions or death. STUDY DESIGN: Stepped wedge cluster randomized trial with cross-sectional measurement at 10 acute care hospitals in Ontario, Canada. Patients presenting during control and intervention periods are eligible if they have a primary ED diagnosis of HF. In the intervention periods, access to the EHMRG30-ST web calculator will become available to hospitals' internet protocol (IP) addresses, and referral to the RAPID-HF clinic will be facilitated by a study nurse navigator. Patients with a high risk EHMRG30-ST score will be admitted to hospital. The RAPID-HF clinic will accept referrals for patients: (1) with low risk 7- and 30-day EHMRG30-ST scores who are discharged directly from the ED, or (2) intermediate risk patients with hospital length of stay < 72 hours. The RAPID-HF clinic, staffed by a nurse-clinician and cardiologist, will provide care during the 30-day transition after hospital separation. CONCLUSION: This trial will determine whether novel risk stratification coupled with rapid ambulatory care achieves better outcomes than conventional decision-making and care for patients with HF.

Derivation and validation of predictive indices for 30-day mortality after coronary and valvular surgery in Ontario, Canada.

BACKGROUND: Coronary artery bypass grafting (CABG) and surgical aortic valve replacement (AVR) are the 2 most common cardiac surgery procedures in North America. We derived and externally validated clinical models to estimate the likelihood of death within 30 days of CABG, AVR or combined CABG + AVR. METHODS: We obtained data from the CorHealth Ontario Cardiac Registry and several linked population health administrative databases from Ontario, Canada. We derived multiple logistic regression models from all adult patients who underwent CABG, AVR or combined CABG + AVR from April 2017 to March 2019, and validated them in 2 temporally distinct cohorts (April 2015 to March 2017 and April 2019 to March 2020). RESULTS: The derivation cohorts included 13 435 patients who underwent CABG (30-d mortality 1.73%), 1970 patients who underwent AVR (30-d mortality 1.68%) and 1510 patients who underwent combined CABG + AVR (30-d mortality 3.05%). The final models for predicting 30-day mortality included 15 variables for patients undergoing CABG, 5 variables for patients undergoing AVR and 5 variables for patients undergoing combined CABG + AVR. Model discrimination was excellent for the CABG (c-statistic 0.888, optimism-corrected 0.866) AVR (c-statistic 0.850, optimism-corrected 0.762) and CABG + AVR (c-statistic 0.844, optimism-corrected 0.776) models, with similar results in the validation cohorts. INTERPRETATION: Our models, leveraging readily available, multidimensional data sources, computed accurate risk-adjusted 30-day mortality rates for CABG, AVR and combined CABG + AVR, with discrimination comparable to more complex American and European models. The ability to accurately predict perioperative mortality rates for these procedures will be valuable for quality improvement initiatives across institutions.

Temporal and Age-Specific Trends in Acute Stroke Incidence: A 15-Year Population-Based Study of Administrative Data in Ontario, Canada.

BACKGROUND: Contemporary data on temporal trends in acute stroke incidence, specific to stroke type and age, are lacking. We sought to evaluate temporal trends in incidence of ischemic stroke and intracerebral hemorrhage over 15 years in a large population. METHODS: We used linked administrative data to identify all emergency department visits and hospital admissions for first-ever ischemic stroke or intracerebral hemorrhage in Ontario, Canada from 2003-2017. We evaluated annual age-/sex-standardized incidence per 100,000 person-years for ischemic stroke and intracerebral hemorrhage across the study period. We used negative binomial regression to determine incidence rate ratios for each year compared to 2003, with assessment of modification by age, sex, or stroke type. RESULTS: Our cohort had 163,574 people with stroke (88% ischemic stroke). For ischemic stroke and intracerebral hemorrhage combined, age-/sex-standardized incidence decreased between 2003 and 2011 (standardized rate 109.4 to 85.8 per 100,000; 22%), then increased until 2017 (standardized rate 96.8 per 100,000; 13%). The pattern of change was similar for ischemic stroke and intracerebral hemorrhage, and for men and women, but was modified by age. For those aged 60 and above, adjusted incidence rate ratios decreased from 2003 to 2011 then subsequently increased, whereas for those aged <60 years incidence rate ratios increased throughout the entire study time period, particularly after 2011. CONCLUSIONS: Acute stroke incidence decreased from 2003 to 2011 but subsequently increased until 2017. Among those aged <60, incidence increased continuously from 2003 to 2017 but especially after 2011. The underlying reasons for these changes should be determined.

Sex differences in direct healthcare costs following stroke: a population-based cohort study.

BACKGROUND: The economic burden of stroke on the healthcare system has been previously described, but sex differences in healthcare costs have not been well characterized. We described the direct person-level healthcare cost in men and women as well as the various health settings in which costs were incurred following stroke. METHODS: In this population-based cohort study of patients admitted to hospital with stroke between 2008 and 2017 in Ontario, Canada, we used linked administrative data to calculate direct person-level costs in Canadian dollars in the one-year following stroke. We used a generalized linear model with a gamma distribution and a log link function to compare costs in women and men with and without adjustment for baseline clinical differences. We also assessed for an interaction between age and sex using restricted cubic splines to model the association of age with costs. RESULTS: We identified 101,252 patients (49% were women, median age [Q1-Q3] was 76 years [65-84]). Unadjusted costs following stroke were higher in women compared to men (mean ± standard deviation cost was $54,012 ± 54,766 for women versus $52,829 ± 59,955 for men, and median cost was $36,703 [$16,496-$72,227] for women versus $32,903 [$15,485-$66,007] for men). However, after adjustment, women had 3% lower costs compared to men (relative cost ratio and 95% confidence interval 0.97 [0.96,0.98]). The lower cost in women compared to men was most prominent among people aged over 85 years (p for interaction = 0.03). Women incurred lower costs than men in outpatient care and rehabilitation, but higher costs in complex continuing care, long-term care, and home care. CONCLUSIONS: Patterns of resource utilization and direct medical costs were different between men and women after stroke. Our findings inform public payers of the drivers of costs following stroke and suggest the need for sex-based cost-effectiveness evaluation of stroke interventions with consideration of costs in all care settings.