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Introduction: Use of bystander-administered naloxone may lead to improved likelihood of recovery from opioid overdose. We sought to determine the accessibility of public access naloxone kits on nearby opioid overdose incidents if placed at public transit stops, compared to placing kits outside pharmacies or with existing public access automated external defibrillators (PADs). Methods: We included all incidents in Metro Vancouver, British Columbia responded to by British Columbia Emergency Health Services coded as a drug overdose with naloxone administered on-scene (Dec. 2014 to Aug. 2020). We geo-coded all public transit bus stops and used a mathematical optimization model to select bus stops where publicly accessible naloxone kits could be placed to maximize accessibility (defined as ≤100 m walking distance) to opioid overdoses. We evaluated accessibility on out-of-sample OHCAs using five-fold cross validation and compared against two baseline policies: placing publicly accessible naloxone kits at all pharmacies identified by the College of Pharmacists of British Columbia, and placing kits at all PADs identified by the British Columbia AED Registry. Statistical analysis was conducted using McNemar’s test. Results: We identified 14,318 opioid overdoses, 8,972 bus stops, 736 pharmacies, and 425 PADs. Accessibility of public naloxone kits for opioid overdose locations was 5.1% when placed at all pharmacies and 3.5% when placed with all existing PADs. Optimized naloxone kit placement using bus stops as candidate locations resulted in significantly higher accessibility than both pharmacy and PAD-based placement at 14.8% with 10 optimized locations (P Conclusion: Optimizing placement of public access naloxone kits at select public transit locations can provide significantly higher accessibility to opioid overdose locations compared to placement at pharmacies or at existing PAD locations.

Introduction: Out-of-hospital cardiac arrest (OHCA) is associated with poor short-term outcomes. However, the impact of pre- and in-hospital factors on long-term outcomes is ill-defined, mainly related to challenges combining disparate data sources. Methods: We linked adult non-traumatic EMS-treated OHCAs from the British Columbia Cardiac Arrest Registry (Jan 2009 - Dec 2016) to provincial datasets describing co-morbidities, medications, procedures, mortality, and hospital admission and discharge. Among hospital-discharge survivors, we examined the 3-year composite endpoint of mortality ± all-cause readmission using the Kaplan-Meier (KM) method and multivariable Cox model for predictors. Results: Of 10,876 successfully linked OHCAs, 1325 survived to hospital discharge: mean age 62.8 years, 77.9% male, 72.6% shockable rhythms, 60.1% non-public locations, 69.1% bystander CPR, and 30.3% STEMI. During admission, 78.6% required mechanical ventilation, 69.1% received coronary angiography (37.5% PCI, 10.3% CABG), and 24.8% received an ICD. At 3 years post-discharge, the estimated KM event rates were 15.9% (95% CI 13.9%, 19.3%) for mortality and 68.2% (95% CI 65.3%, 71.0%) for mortality and readmission, which differed by age, initial rhythm, and arrest location ( Figure ). Following multivariable analysis, patients with a history of HF [HR 1.62 (95% CI 1.34 - 1.96)], age >75 [1.62 (1.35, 1.96)], anticoagulation use [2.55 (1.36, 4.79)], non-shockable rhythm [1.29 (1.07, 1.55)] and non-public arrest location [1.21(1.04, 1.40)] were more likely to experience the composite endpoint; those receiving coronary angiography were less likely [0.79 (0.64, 0.98)]. Conclusions: The long-term death or readmission risk persists even among OHCA hospital-discharge survivors, and is associated with both pre- and in-hospital factors. An enriched, linked dataset detailing the entire OHCA “journey” may be a promising tool to identify care and treatment gaps.

Patients with atrial fibrillation (AF) have a significant increased risk of embolic stroke. Patients with end-stage renal disease who are on dialysis have an increased risk of both embolic stroke and bleeding. Stroke-prevention studies with the use of anticoagulation for AF patients have excluded patients on dialysis, so there remains no consensus on their management. We developed and implemented a pan-Canadian multidisciplinary survey to explore the current beliefs and practices concerning patients with AF on dialysis. We developed an online investigator-designed survey with both quantitative and qualitative responses with the use of a secure university-affiliated electronic service. The survey was distributed to physicians via the QxMD platform and directly to internal medicine, cardiology, and nephrology residency program directors for distribution to faculty members. 130 participants responded, including 46 cardiologists, 45 nephrologists, 30 general internists, and 9 other physicians. The preferred anticoagulant was warfarin. The CHADS2 score used to initiate anticoagulation was highly variable, with specialties differing in use of a CHADS2 threshold of ≥ 1 (P

Background CODE-MI is a pan-Canadian, multicentre, stepped-wedge, cluster randomized trial that evaluates the impact of using the female-specific 99th percentile threshold for high-sensitivity cardiac troponin (hs-cTn) on the diagnosis, treatment and outcomes of women presenting to the emergency department (ED) with symptoms suggestive for myocardial ischemia. A feasibility study was conducted to estimate the number of eligible patients, the rate of the study's primary outcome under control conditions, and the statistical power to detect a clinically important difference in the primary outcome. Methods Using linked administrative data from 11 hospitals in Ontario, Canada, from October 2014 to September 2017, the following estimates were obtained: number of women presenting to the ED with symptoms suggestive of myocardial ischemia and a 24-hour peak hs-cTn value within the female-specific and overall thresholds (ie, primary cohort); the rate of the 1-year composite outcome of all-cause mortality, re-admission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization. Study power was evaluated via simulations. Results Overall, 2,073,849 ED visits were assessed. Among women, chest pain (with or without cardiac features) and shortness of breath were the most common complaints associated with a diagnosis of acute coronary syndrome. An estimated 7.7% of women with these complaints are eligible for inclusion in the primary cohort. The rate of the 1-year outcome in the primary cohort varied significantly across hospitals with a median rate of 12.2% (95%CI: 7.9%-17.7%). With 30 hospitals, randomized at 5-month intervals in 5 steps, approximately 19,600 women are expected to be included in CODE-MI, resulting in >82% power to detect a 20% decrease in the odds of the primary outcome at a 0.05 significance level. Conclusions This feasibility study greatly enhanced the design of CODE-MI, allowed accurate evaluation of the study power, and demonstrated the strength of using linked administrative health data to guide the design of pragmatic clinical trials.

Background Despite evidence that high-sensitivity cardiac troponin (hs-cTn) levels in women are lower than in men, a single threshold based on the 99th percentile upper reference limit of the overall reference population is commonly used to diagnose myocardial infarction in clinical practice. This trial aims to determine whether the use of a lower female-specific hs-cTn threshold would improve the diagnosis, treatment, and outcomes of women presenting to the emergency department with symptoms suggestive of myocardial ischemia. Methods/Design CODE-MI (hs-cTn—Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women) is a multicenter, stepped-wedge, cluster-randomized trial of 30 secondary and tertiary care hospitals across 8 Canadian provinces, with the unit of randomization being the hospital. All adults (≥20 years of age) presenting to the emergency department with symptoms suggestive of myocardial ischemia and at least 1 hs-cTn test are eligible for inclusion. Over five, 5-month intervals, hospitals will be randomized to implement lower female hs-cTn thresholds according to the assay being used at each site. Men will continue to be assessed using the overall thresholds throughout. Women with a peak hs-cTn value between the female-specific and the overall thresholds will form our primary cohort. The primary outcome, a 1-year composite of all-cause mortality or readmission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization, will be compared before and after the implementation of female thresholds using mixed-effects logistic regression models. The cohort and outcomes will be obtained from routinely collected administrative data. The trial is designed to detect a 20% relative risk difference in the primary outcome, or a 2.2% absolute difference, with 82% power. Conclusions This pragmatic trial will assess whether adopting lower female hs-cTn thresholds leads to appropriate assessment of women with symptoms suggestive of myocardial infarction, thereby improving treatment and outcomes.

Elevated cardiac troponin (cTn), with signs/symptoms of ischemia, is a key element in a diagnosis of myocardial infarction (MI). Underdiagnosis of MI in women has been attributed to atypical symptoms, inconsistent ECG findings, and less diagnostic testing. We sought to determine if there are sex differences in cTn testing following presentation to the emergency department (ED) with a chief complaint of ischemic chest pain (CP) and if presentation affects diagnostic assessment.All adults presenting to six hospital EDs in the Vancouver, Canada with a chief complaint of ischemic CP from 2009 to 2013 were included. The highest cTn level within 24 hours of ED presentation was used. CP was classified into cardiac- or respiratory dominant based on standard Canadian Emergency Department Triage and Acuity Scale coding. Chi-square testing was used to test for sex differences in CP categories and cTn testing within 24 hours. Logistic regression models were used to examine the association between sex, cTn testing, and CP categories.Of 27,063 patients with ischemic CP, cardiac presentation was more common in men than women, irrespective of age. Among cardiac CP, 24.7% of men were50 years compared to 18.2% of women; however, more women (19.9%) than men (11.6%) were80 years. Overall, women were 1.8% less likely to have cTn testing; in patients50 years, testing was markedly lower in women compared to men [odds ratio, OR (95% confidence intervals, CI) 0.78 (0.70-0.87)]. The odds of cardiac catheterization within 90 days of ED presentation were lower in women [OR, (95% CI) 0.52 (0.44-0.63)]. Even with cardiac CP, 17.7% of women versus 32.7% of men had cardiac catheterization.In men and women presenting to the ED with ischemic CP, cTn testing overall is similar except among young women under 50 years old, where it is markedly lower. Women undergo less cardiac catheterization, irrespective of CP type.

While sex differences in the treatment and outcomes of subjects with acute coronary syndromes are well documented, little is known about the impact of cardiac troponin (cTn) levels obtained in the emergency department (ED) on the observed sex differences. We sought to determine whether cTn levels by chest pain features modify sex differences in diagnosis, treatment, and outcomes in patients presenting with chest pain suggestive of ischemia.All adults presenting to two hospitals in Vancouver, Canada, between May 2008 and March 2013 with ischemic chest pain and with cTn testing were included in the study. Outcomes were obtained through data linkage with population-based administrative data sets, including Vital Statistics (death), Discharge Abstract Database (hospitalizations), and PharmaNet (medications). Cumulative event rates for the composite major adverse cardiac event (MACE) endpoint (death, myocardial infarction [MI], incident admission for heart failure or for angina requiring diagnostic catheterization or revascularization) were estimated for each sex and cTn level using the Kaplan-Meier method; Cox models were used to estimate hazard ratios and 95% confidence interval (CIs) for 1-year MACE and 7-day catheterization. Logistic models were used to estimate odds ratios (ORs) and 95% CI for 90-day medication use.Over the 5-year study period, 25,539 patients presented to the ED with chest pain of which 7,272 (2,933 females and 4,339 males) met the inclusion criteria. Among patients with chest pain with cardiac features/history and cTn 99th percentile, females were less likely to be diagnosed with MI (46.4% vs. 57.5%). Females in the cTnI 99th percentile group had the worst outcomes with a 1-year MACE rate of 22.7% (95% CI = 18.5-27.7) versus 18.8% (95% CI = 16.2-21.6), although this difference was attenuated and not statistically significant after adjustment for baseline differences. Overall, females underwent fewer diagnostic catheterizations than males within 7 days of admission to the ED. Even when cTn was above the 99th percentile and the chest pain was cardiac in nature, 48.4% of females underwent a diagnostic catheterization compared to 64.3% of males (p 0.001). Within 90 days of discharge, females were less likely to use the evidence-based cardiac medications. The most striking sex differences were noted when cTnI levels were 99th percentile and when the chest pain was cardiac in nature; males filled 25% more prescriptions for statins than their female counterparts. Adjustment for baseline differences did not attenuate this difference.Sex differences in diagnosis and treatment after presentation to the ED with chest pain are not explained by differences in chest pain features or levels of cTn. Even when females have cardiac chest pain and cTn levels 99th percentile, they are less likely to be diagnosed with MI, less likely to undergo diagnostic cardiac catheterization within 7 days, and less likely to use evidence-based cardiac medications, but they have the highest 1-year MACE rate. The higher MACE rate appears to be driven by the higher burden of comorbid conditions.

Recent research has identified younger women as an "at-risk" population with rising prevalence of cardiac risk factors and excess mortality risk following acute myocardial infarction (AMI). However, population-based data on trends in AMI hospitalization and early mortality post AMI among younger adults is scarce. We, therefore, aimed to provide a 10-year, descriptive analysis of these trends in a Canadian setting.We assessed trends and sex differences in AMI hospitalization and 30-day mortality rates using negative binomial and logistic regression, respectively. From 2000 to 2009, there were 70,628 AMI hospitalizations in adults aged ≥20 years, in British Columbia, Canada, with 17.1% of cohort being younger adults ≤55 years. Overall, age-standardized AMI rates (per 100,000 population) declined similarly in men (295.8 to 247.7) and women (152.1 to 128.8) [sex-year interaction p=0.81]. However, these trends differed according to age (age-sex-year interaction p=0.02) with increased rates observed only in younger women (+1.7% per year; p=0.04). The 30-day mortality rates declined similarly for women (19.4% to 13.9%) and men (13.0% to 9.3%) (sex-year interaction p=0.33). Yet, younger women continued to have excess mortality risk, compared with younger men, even in the most recent period [odds ratio: (2008-09)=1.61 (95% onfidence interval: 1.25, 2.08)].While the overall AMI hospitalization and 30-day mortality rates significantly declined in women and men, hospitalization rates in women ≤55 years increased and their excess risk of 30-day mortality persisted. These findings highlight the need to intensify strategies to reduce the incidence of AMI and improve outcomes after AMI in younger women.

Background— The joint contribution of sex, ethnicity, and initial clinical presentation to the long-term outcomes of patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina, in whom there is angiographic evidence for obstructive coronary artery disease, remains unknown. Methods and Results— We conducted a population-based cohort study on 49 556 adult ACS or stable angina patients with angiographic evidence of obstructive coronary artery disease (≥50% stenosis) in British Columbia. The 2-year composite outcome was all-cause death and hospital readmissions for myocardial infarction, heart failure, cerebrovascular accident, or angina after the index angiography. Sex and ethnic differences in the composite outcome were examined by clinical presentation using the Cox proportional-hazards and logistic regression models. Overall, 25.6% were women, 9.5% were South Asians, 3.0% were Chinese, and 65.9% presented with ACS. Regardless of ethnicity, women were more likely than men to have adverse outcomes, but the magnitude of the sex difference was greater in the ACS patients ( P interaction for sex and clinical presentation=0.03). Angina readmission accounted for 45% of the composite outcome and was the main component for all groups with the exception of Chinese women with ACS. Furthermore, women were more likely than men to be readmitted for angina (odds ratio [95% confidence interval], 1.13 [1.04–1.22]). Conclusions— Higher rates of adverse events among women with obstructive coronary artery disease, regardless of ethnicity, as well as high rates of angina readmission, highlight the need for more targeted interventions to reduce the burden of angina because this presentation is clearly not benign.

Background: Acute myocardial infarction (AMI) patients are frequently transferred to tertiary care facilities for advanced procedures. Exclusion of transferred patients can result in biased estimates, especially if the focus is on a population-based cohort. The potential magnitude of this bias remains unknown. We assessed the impact of excluding transferred patients on 30-day AMI mortality estimates, over a 10-year period. Methods: All AMI hospitalizations to acute care hospitals in British Columbia, from 2000 to 2009, were captured. Transfers were defined as a discharge from the index AMI hospitalization to another hospital. We compared transfer rates by sex, age and year using logistic regression models. Age- and sex-specific 30-day AMI mortality rates and the sex odds ratios (OR) were estimated, regardless of transfer status, and for the sub-cohort excluding transferred patients. Results: Of 63,310 AMI patients, 40.6% had at least one transfer out of the index AMI hospital. Men and younger patients were more likely to be transferred. Transfer rates increased over time in all age groups regardless of sex. Overall, when transfers were excluded, 30-day AMI mortality rates were overestimated (absolute difference of 5.5% in women and 6.7% in men). Furthermore, the 30-day mortality OR (women vs. men) was underestimated: transfer outs excluded (OR=1.25, 95% CI: 1.19, 1.31) vs. all patients included (OR=1.49, 95% CI: 1.42, 1.56). Conclusions: 30-day mortality may be overestimated in population-based analyses when transfers are excluded, while the sex difference is underestimated. The observed bias is strongly affected by the magnitude and time trends of transfer rates.

Objectives The aim of this study was to examine sex differences in outcome after transcatheter aortic valve replacement (TAVR) with real-world data from 2 large centers in Canada. Background Transcatheter aortic valve replacement is an effective alternative to surgical valve replacement in symptomatic patients with severe aortic stenosis, but the impact of sex on outcomes remains unclear. The PARTNER (Placement of Aortic Transcatheter Valves) 1A trial demonstrated greater benefit of TAVR over surgery in women, but whether this was due to the poorer surgical outcome of women or better TAVR outcome, compared with men, is unknown. Methods Consecutive patients (n = 641) undergoing TAVR in Vancouver and Quebec City, Canada, were evaluated. Differences in all-cause mortality were examined with Kaplan-Meier estimates, adjusted logistic regression, and proportional hazards models. Results Women comprised 51.3% of the cohort. Balloon-expandable valves were used in 97% of cases, with transapical approach in 51.7 % women and 38.1% men. Women had more major vascular complications (12.4% vs. 5.4%, p = 0.003) and borderline significantly more major/life-threatening bleeds (21.6% vs. 15.8%, p = 0.08). At baseline, women had higher aortic gradients and worse renal function but better ejection fractions. Men had more comorbidities: prior myocardial infarction, prior revascularization, and chronic obstructive pulmonary disease. The adjusted odds ratio for 30-day all-cause mortality favored women, 0.39 (95% confidence interval: 0.19 to 0.80; p = 0.01), and this benefit persisted for 2 years, hazard ratio 0.60 (95% confidence interval: 0.41 to 0.88; p = 0.008). Conclusions Female sex is associated with better short- and long-term survival after TAVR. Added to the PARTNER 1A findings, these results suggest TAVR might be the preferred treatment option for elderly women with symptomatic severe aortic stenosis.

Introduction: Patients hospitalized for an AMI are commonly transferred to tertiary care facilities to receive advanced procedures. In the United States, transferred patients are often excluded from outcome evaluations due to limitations in ascertaining outcomes. In Canada, centralized administrative and clinical databases allow for linkage of outcomes across institutions. This study evaluated the influence of excluding transferred AMI patients on estimates of age and sex-specific 30-day mortality rates over a 10-year period. Methods: All incident AMI hospitalizations (ICD-9: 410 and ICD-10: I21, I22) to acute care hospitals in British Columbia from 2000 to 2009 were identified through the Discharge Abstract Database and linked to mortality through the Vital Statistics registry. A transfer was identified as a discharge from the index AMI admission hospital to another hospital. Thirty-day mortality was defined as any death within 30 days of the index hospitalization. A logistic regression model was used to compare transfer rate by age (20-55, 56-64, 65-74 and ≥ 75 years), sex and admission year. Thirty-day mortality rates by sex and age were calculated with and without transferred patients. Results: Of the 67,444 AMI hospitalizations identified, 38.6% involved at least one transfer. Overall, younger patients were more likely to be transferred. Transfer rates increased over time in all age groups but with different slopes (p = 0.02) regardless of sex, and differed significantly between sexes only in those ≥ 75 (p < 0.001; Fig. A). Thirty-day mortality rates were overestimated in each age-sex category when transferred patients were excluded, compared to rates that included all patients, irrespective of transfer status (Fig. B). Conclusions: The rate of patient transfers post AMI has increased over time. Excluding transferred patients results in overestimates of 30-day mortality, and thus impacts outcome assessments. This impact is expected to increase over time.

Background— Atrial arrhythmias (AA) are an important cause of morbidity after cardiac surgery. Efforts at prevention of postoperative AA have been suboptimal. Perioperative beta-blocker administration is the standard of care at many centers. Although prophylactic administration of magnesium sulfate (MgSO 4 ) has been recommended, review of all previously published trials of MgSO 4 reveals conflicting results. This study was designed to address methodological shortcomings from previous studies and is the largest randomized, placebo-controlled trial of intravenous (IV) MgSO 4 for the prevention of AA after coronary artery bypass grafting or cardiac valvular surgery. Methods and Results— A total of 927 nonemergent cardiac surgery patients were stratified into 2 groups: isolated coronary artery bypass grafting (n=694), or valve surgery with or without coronary artery bypass grafting (n=233), and randomized to receive either 5g IV MgSO 4 or placebo on removal of the cross-clamp, followed by daily 4-hour infusions, from postoperative day 1 until postoperative day 4. All patients were treated according to an established oral β-blocker protocol. Postoperative serum Mg levels were checked and standard of care was to administer IV MgSO 4 for low serum levels. The primary end point was AA lasting ≥30 minutes or requiring treatment for hemodynamic compromise. There were no differences in the incidence of AA between patients who received IV MgSO 4 or placebo (26.4% versus 24.3%, respectively). The results were similar when broken down according to stratified groups. Conclusions— In patients treated with a protocol for postoperative oral β-blocker after nonemergent cardiac surgery, the addition of prophylactic IV MgSO 4 did not reduce the incidence of AA.

Background Atrial arrhythmias (AA) affect up to 40% of patients following cardiac surgery. The best strategy for prevention of AA remains undetermined, however, beta blocker (BB) administration is the standard of care at many centers (including ours). Although there is now compelling evidence demonstrating the utility of magnesium sulphate (MgSO4) for treatment of AA, the effectiveness of MgSO4 for prophylaxis of AA remains controversial. This study is the largest randomized, placebo-controlled trial of intravenous (IV) MgSO4 for the prevention of AA following cardiac surgery. Methods Eligible patients requiring either coronary artery bypass graft surgery (CABG), or valve surgery ± CABG, were randomized to receive either 5g IV MgSO4, or placebo upon removal of the crossclamp, followed by daily infusions of IV MgSO4 or placebo over 4 hours, from the day of surgery until post-operative day 4. All patients were treated according to an established protocol with oral BB (atenolol). Patients were monitored by continuous telemetry for the first 5 post-operative days. The primary endpoint was an AA lasting ≥ 30 minutes, or requiring treatment because of hemodynamic compromise. Results Table 1 summarizes the results. There was no difference in the incidence of AA between patients who received IV MgSO4 or those who received placebo. Conclusions In patients proactively treated with atenolol using an established protocol, the addition of daily IV MgSO4 infusions for 5 days post-operatively did not reduce the incidence of clinically important AA following cardiac surgery. Results For Primary Outcome (Post-Operative AA)

ObjectiveLong-term survival after aortic surgery has remained largely unexplored, despite suggestions of superior durability compared with endovascular techniques. The objective of the present study was to determine the long-term survival after open thoracic aortic surgery and to identify the predictors of mortality.MethodsThe provincial database was accessed to identify all adult patients who had undergone primary open thoracic aortic surgery in British Columbia since 1993. Kaplan-Meier survival analyses were performed for the entire group and by year of surgery, urgency of surgery, and aortic segment requiring surgery. Multivariate analyses were performed to identify the predictors of mortality.ResultsFrom January 1993 to June 2010, 1960 patients underwent primary open thoracic aortic surgery at 4 hospitals in British Columbia. Overall, the 30-day mortality was 9.1%, with a perioperative stroke rate of 5.8%. Long-term survival was 77.7%, 59.6%, and 44.7% at 5, 10, and 15 years, respectively. Subanalyses demonstrated improved long-term survival in the modern era; among patients undergoing elective aortic surgery; and among patients undergoing surgery on the ascending aorta or aortic root (P