Sex-Based Differences in Severe Outcomes, Including Cardiovascular Hospitalization, in Adults With COVID-19 in Ontario, Canada.

Background: While men have experienced higher risks of SARS-CoV-2 infection compared to women, an analysis of sex differences by age in severe outcomes during the acute phase of infection is lacking. Objectives: The purpose of this study was to assess heterogeneity in severe outcome risks by age and sex by conducting a retrospective cohort study of community-dwelling adults in Ontario who tested positive for SARS-CoV-2 infection during the first 3 waves. Methods: Adjusted odds ratios were estimated using multilevel multivariable logistic regression models including an interaction term for age and sex. The primary outcome was a composite of severe outcomes (hospitalization for a cardiovascular (CV) event, intensive care unit admission, mechanical ventilation, or death) within 30 days. Results: Among 30,736, 199,132, and 186,131 adults who tested positive during the first 3 waves, 1,908 (6.2%), 5,437 (2.7%), and 5,653 (3.0%) experienced a severe outcome within 30 days. For all outcomes, the sex-specific risk depended on age (all P for interaction <0.05). Men with SARS-CoV-2 infection experienced a higher risk of outcomes than infected women of the same age, except for the risk of all-cause hospitalization being higher for young women than men (ages 18-45 years) during waves 2 and 3. The sex disparity in CV hospitalization across all ages either persisted or increased with each subsequent wave. Conclusions: To mitigate risks in subsequent waves, it is helpful to further understand the factors that contribute to the generally higher risks faced by men across all ages, and the persistent or increasing sex disparity in the risk of CV hospitalization.

Comorbidity-stratified estimates of 30-day mortality risk by age for unvaccinated men and women with COVID-19: a population-based cohort study.

BACKGROUND: The mortality risk following COVID-19 diagnosis in men and women with common comorbidities at different ages has been difficult to communicate to the general public. The purpose of this study was to determine the age at which unvaccinated men and women with common comorbidities have a mortality risk which exceeds that of 75- and 65-year-old individuals in the general population (Phases 1b/1c thresholds of the Centre for Disease Control Vaccine Rollout Recommendations) following COVID-19 infection during the first wave. METHODS: We conducted a population-based retrospective cohort study using linked administrative datasets in Ontario, Canada. We identified all community-dwelling adults diagnosed with COVID-19 between January 1 and October 31st, 2020. Exposures of interest were age (modelled using restricted cubic splines) and the following conditions: major cardiovascular disease (recent myocardial infarction or lifetime history of heart failure); 2) diabetes; 3) hypertension; 4) recent cancer; 5) chronic obstructive pulmonary disease; 6) Stages 4/5 chronic kidney disease (CKD); 7) frailty. Logistic regression in the full cohort was used to estimate the risk of 30-day mortality for 75- and 65-year-old individuals. Analyses were repeated after stratifying by sex and medical condition to determine the age at which 30-day morality risk in strata exceed that of the general population at ages 65 and 75 years. RESULTS: We studied 52,429 individuals (median age 42 years; 52.5% women) of whom 417 (0.8%) died within 30 days. The 30-day mortality risk increased with age, male sex, and comorbidities. The 65- and 75-year-old mortality risks in the general population were exceeded at the youngest age by people with CKD, cancer, and frailty. Conversely, women aged < 65 years who had diabetes or hypertension did not have higher mortality than 65-year-olds in the general population. Most people with medical conditions (except for Stage 4-5 CKD) aged < 45 years had lower predicted mortality than the general population at age 65 years. CONCLUSION: The mortality risk in COVID-19 increases with age and comorbidity but the prognostic implications varied by sex and condition. These observations can support communication efforts and inform vaccine rollout in jurisdictions with limited vaccine supplies.

Health Care Implications of the COVID-19 Pandemic for the Cardiovascular Practitioner.

There has been substantial excess morbidity and mortality during the COVID-19 pandemic, not all of which was directly attributable to SARS-CoV-2 infection, and many non-COVID-19 deaths were cardiovascular. The indirect effects of the pandemic have been profound, resulting in a substantial increase in the burden of cardiovascular disease and cardiovascular risk factors, both in individuals who survived SARS-CoV-2 infection and in people never infected. In this report, we review the direct effect of SARS-CoV-2 infection on cardiovascular and cardiometabolic disease burden in COVID-19 survivors as well as the indirect effects of the COVID-19 pandemic on the cardiovascular health of people who were never infected with SARS-CoV-2. We also examine the pandemic effects on health care systems and particularly the care deficits caused (or exacerbated) by health care delayed or foregone during the COVID-19 pandemic. We review the consequences of: (1) deferred/delayed acute care for urgent conditions; (2) the shift to virtual provision of outpatient care; (3) shortages of drugs and devices, and reduced access to: (4) diagnostic testing, (5) cardiac rehabilitation, and (6) homecare services. We discuss the broader implications of the COVID-19 pandemic for cardiovascular health and cardiovascular practitioners as we move forward into the next phase of the pandemic.

Healthcare implications of the COVID-19 pandemic for the cardiovascular practitioner

There has been substantial excess morbidity and mortality during the COVID-19 pandemic, not all of which was directly attributable to SARS-CoV-2 infection, and many non-COVID-19 deaths were cardiovascular. The indirect effects of the pandemic have been profound, resulting in a substantial rise in the burden of cardiovascular disease and cardiovascular risk factors, both in individuals who survived SARS-CoV-2 infection and in people never infected. In this manuscript, we review the direct impact of SARS-CoV-2 infection on cardiovascular and cardiometabolic disease burden in COVID-19 survivors as well as the indirect impacts of the COVID-19 pandemic on the cardiovascular health of people who were never infected with SARS-CoV-2. We also examine the pandemic impacts on healthcare systems and particularly the care deficits caused (or exacerbated) by healthcare delayed or foregone during the COVID-19 pandemic. We review the consequences of (i) deferred/delayed acute care for urgent conditions, (ii) the shift to virtual provision of outpatient care, (iii) shortages of drugs and devices, and reduced access to (iv) diagnostic testing, (v) cardiac rehabilitation, and (vi) homecare services. We discuss the broader implications of the COVID-19 pandemic for cardiovascular health and cardiovascular practitioners as we move forward into the next phase of the pandemic.

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).

Telemedicine use and outcomes after transient ischemic attack and minor stroke during the COVID-19 pandemic: a population-based cohort study.

BACKGROUND: The COVID-19 pandemic has led to an increase in telemedicine use. We compared care and outcomes in patients with transient ischemic attack (TIA) or minor ischemic stroke before and after the widespread adoption of telemedicine in Ontario, Canada, in 2020. METHODS: In a population-based cohort study using linked administrative data, we identified patients with TIA or ischemic stroke discharged from any emergency department in Ontario before the widespread use of telemedicine (Apr. 1, 2015, to Mar. 31, 2020) and after (Apr. 1, 2020, to Mar. 31, 2021). We measured care, including visits with a physician, investigations and medication renewal. We compared 90-day death before and after 2020 using Cox proportional hazards models, and we compared 90-day admission using cause-specific hazard models. RESULTS: We identified 47 601 patients (49.3% female; median age 73, interquartile range 62-82, yr) with TIA (n = 35 695, 75.0%) or ischemic stroke (n = 11 906, 25.0%). After 2020, 83.1% of patients had 1 or more telemedicine visit within 90 days of emergency department discharge, compared with 3.8% before. The overall access to outpatient visits within 90 days remained unchanged (92.9% before v. 94.0% after; risk difference 1.1, 95% confidence interval [CI] -1.3 to 3.5). Investigations and medication renewals were unchanged. Clinical outcomes were also similar before and after 2020; the adjusted hazard ratio was 0.97 (95% CI 0.91 to 1.04) for 90-day all-cause admission, 1.06 (95% CI 0.94 to 1.20) for stroke admission and 1.07 (95% CI 0.93 to 1.24) for death. INTERPRETATION: Care and short-term outcomes after TIA or minor stroke remained stable after the widespread implementation of telemedicine during the COVID-19 pandemic. Our findings suggest that telemedicine is an effective method of health care delivery that can be complementary to in-person care for minor ischemic cerebrovascular events.

Relationship of frailty with excess mortality during the COVID-19 pandemic: a population-level study in Ontario, Canada.

BACKGROUND: There is a paucity of the literature on the relationship between frailty and excess mortality due to the COVID-19 pandemic. METHODS: The entire community-dwelling adult population of Ontario, Canada, as of January 1st, 2018, was identified using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) cohort. Residents of long-term care facilities were excluded. Frailty was categorized through the Johns Hopkins Adjusted Clinical Groups (ACG® System) frailty indicator. Follow-up was until December 31st, 2020, with March 11th, 2020, indicating the beginning of the COVID-19 pandemic. Using multivariable Cox models with patient age as the timescale, we determined the relationship between frailty status and pandemic period on all-cause mortality. We evaluated the modifier effect of frailty using both stratified models as well as incorporating an interaction between frailty and the pandemic period. RESULTS: We identified 11,481,391 persons in our cohort, of whom 3.2% were frail based on the ACG indicator. Crude mortality increased from 0.75 to 0.87% per 100 person years from the pre- to post-pandemic period, translating to ~ 13,800 excess deaths among the community-dwelling adult population of Ontario (HR 1.11 95% CI 1.09-1.11). Frailty was associated with a statistically significant increase in all-cause mortality (HR 3.02, 95% CI 2.99-3.06). However, all-cause mortality increased similarly during the pandemic in frail (aHR 1.13, 95% CI 1.09-1.16) and non-frail (aHR 1.15, 95% CI 1.13-1.17) persons. CONCLUSION: Although frailty was associated with greater mortality, frailty did not modify the excess mortality associated with the pandemic.

Clinical risk, sociodemographic factors, and SARS-CoV-2 infection over time in Ontario, Canada.

We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction < 0.0001). Prior to the first-wave peak, SARS-CoV-2 infection increased with age whereas this association reversed thereafter. Risk factors that persisted included male sex, residing in lower income neighborhoods, residing in more racially/ethnically diverse communities, immigration to Canada, hypertension, and diabetes. While there was a reduction in infection rates after mid-April 2020, there was less impact in regions with higher racial/ethnic diversity. Immediately following the initial peak, individuals living in the most racially/ethnically diverse communities with 2, 3, or ≥ 4 risk factors had ORs of 1.89, 3.07, and 4.73-fold higher for SARS-CoV-2 infection compared to lower risk individuals in their community (all P < 0.0001). In the latter half of 2020, this disparity persisted with corresponding ORs of 1.66, 2.48, and 3.70-fold higher, respectively. In the least racially/ethnically diverse communities, there was little/no gradient in infection rates across risk strata. Further efforts are necessary to reduce the risk of SARS-CoV-2 infection among the highest risk individuals residing in the most racially/ethnically diverse communities.

The risk of death or unplanned readmission after discharge from a COVID-19 hospitalization in Alberta and Ontario.

BACKGROUND: The frequency of readmissions after COVID-19 hospitalizations is uncertain, as is whether current readmission prediction equations are useful for discharge risk stratification of COVID-19 survivors or for comparing among hospitals. We sought to determine the frequency and predictors of death or unplanned readmission after a COVID-19 hospital discharge. METHODS: We conducted a retrospective cohort study of all adults (≥ 18 yr) who were discharged alive from hospital after a nonpsychiatric, nonobstetric, acute care admission for COVID-19 between Jan. 1, 2020, and Sept. 30, 2021, in Alberta and Ontario. RESULTS: Of 843 737 individuals who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction during the study period, 46 412 (5.5%) were adults admitted to hospital within 14 days of their positive test. Of these, 8496 died in hospital and 34 846 were discharged alive (30 336 discharged after an index admission of ≤ 30 d and 4510 discharged after an admission > 30 d). One in 9 discharged patients died or were readmitted within 30 days after discharge (3173 [10.5%] of those with stay ≤ 30 d and 579 [12.8%] of those with stay > 30 d). The LACE score (length of stay, acuity, Charlson Comorbidity Index and number of emergency visits in previous 6 months) for predicting urgent readmission or death within 30 days had a c-statistic of 0.60 in Alberta and 0.61 in Ontario; inclusion of sex, discharge locale, deprivation index and teaching hospital status in the model improved the c-statistic to 0.73. INTERPRETATION: Death or readmission after discharge from a COVID-19 hospitalization is common and had a similar frequency in Alberta and Ontario. Risk stratification and interinstitutional comparisons of outcomes after hospital admission for COVID-19 should include sex, discharge locale and socioeconomic measures, in addition to the LACE variables.

Association of Influenza Vaccination With Cardiovascular Risk: A Meta-analysis.

Importance: Influenza infection is associated with increased cardiovascular hospitalization and mortality. Our prior systematic review and meta-analysis hypothesized that influenza vaccination was associated with a lower risk of cardiovascular events. Objective: To evaluate, via an updated meta-analysis, if seasonal influenza vaccination is associated with a lower risk of fatal and nonfatal cardiovascular events and assess whether the newest cardiovascular outcome trial results are consistent with prior findings. Data Sources: A previously published meta-analysis of randomized controlled trials (RCTs) and a large 2021 cardiovascular outcome trial. Study Selection: Studies with RCTs published between 2000 and 2021 that randomized participants to either influenza vaccine or placebo/control. Eligible participants were inpatients and outpatients recruited for international multicenter RCTs and randomized to receive either influenza vaccine or placebo/control. Data Extraction and Synthesis: PRISMA guidelines were followed in the extraction of study details, and risk of bias was assessed using the Cochrane Collaboration tool. Trial quality was evaluated using Cochrane criteria. Data were analyzed January 2020 and December 2021. Main Outcomes and Measures: Random-effects Mantel-Haenszel risk ratios (RRs) and 95% CIs were derived for a composite of major adverse cardiovascular events and cardiovascular mortality within 12 months of follow-up. Where available, analyses were stratified by patients with and without recent acute coronary syndrome (ACS) within 1 year of randomization. Results: Six published RCTs comprising a total of 9001 patients were included (mean age, 65.5 years; 42.5% women; 52.3% with a cardiac history). Overall, influenza vaccine was associated with a lower risk of composite cardiovascular events (3.6% vs 5.4%; RR, 0.66; 95% CI, 0.53-0.83; P < .001). A treatment interaction was detected between patients with recent ACS (RR, 0.55; 95% CI, 0.41-0.75) and without recent ACS (RR, 1.00; 95% CI, 0.68-1.47) (P for interaction = .02). For cardiovascular mortality, a treatment interaction was also detected between patients with recent ACS (RR, 0.44; 95% CI, 0.23-0.85) and without recent ACS (RR, 1.45; 95% CI, 0.84-2.50) (P for interaction = .006), while 1.7% of vaccine recipients died of cardiovascular causes compared with 2.5% of placebo or control recipients (RR, 0.74; 95% CI, 0.42-1.30; P = .29). Conclusions and Relevance: In this study, receipt of influenza vaccination was associated with a 34% lower risk of major adverse cardiovascular events, and individuals with recent ACS had a 45% lower risk. Given influenza poses a threat to population health during the COVID-19 pandemic, it is integral to counsel high-risk patients on the cardiovascular benefits of influenza vaccination.

The impact of shifting demographics, variants of concern and vaccination on outcomes during the first 3 COVID-19 waves in Alberta and Ontario: a retrospective cohort study.

BACKGROUND: In Canada, published outcome data for COVID-19 come largely from the first 2 waves of the pandemic. We examined changes in demographics and 30-day outcomes after SARS-CoV-2 infection during the first 3 pandemic waves in Alberta and Ontario; for wave 3, we compared outcomes between those infected with a variant of concern and those infected with the original "wild-type" SARS-CoV-2. METHODS: We conducted a population-based retrospective cohort study using linked health care data sets in Alberta and Ontario. We identified all-cause hospitalizations or deaths within 30 days after a positive result on a reverse transcription polymerase chain reaction test for SARS-CoV-2 in individuals of any age between Mar. 1, 2020, and June 30, 2021, with genomic confirmation of variants of concern. We compared outcomes in wave 3 (February 2021 to June 2021) with outcomes in waves 1 and 2 combined (March 2020 to January 2021) after adjusting for age, sex and Charlson Comorbidity Index score. Using wave 3 data only, we compared outcomes by vaccination status and whether or not the individual was infected with a variant of concern. RESULTS: Compared to those infected with SARS-CoV-2 during waves 1 and 2 (n = 372 070), we found a shift toward a younger and healthier demographic in those infected during wave 3 (n = 359 079). In wave 3, patients were more likely to be hospitalized (adjusted odds ratio [aOR] 1.57, 95% confidence interval [CI] 1.46-1.70) but had a shorter length of hospital stay (median 6 days v. 7 days, p < 0.001) and lower 30-day mortality (aOR 0.73, 95% CI 0.65-0.81). The 217 892 patients in wave 3 who were infected with a variant of concern (83.5% confirmed to have the Alpha variant, 1.7% confirmed to have the Delta variant) had a higher risk of death (Alpha: aOR 1.29, 95% CI 1.16-1.44; Delta: aOR 2.05, 95% CI 1.49-2.82) and hospitalization (Alpha: aOR 1.59, 95% CI 1.53-1.66; Delta: aOR 1.88, 95% CI 1.64-2.15) than those infected with wild-type SARS-CoV-2. INTERPRETATION: We observed a shift among those infected with SARS-CoV-2 toward younger patients with fewer comorbidities, a shorter length of hospital stay and lower mortality risk as the pandemic evolved in Alberta and Ontario; however, infection with a variant of concern was associated with a substantially higher risk of hospitalization or death. As variants of concern emerge, ongoing monitoring of disease expression and outcomes among vaccinated and unvaccinated individuals is important to understand the phenotypes of COVID-19 and the anticipated burdens for the health care system.

Derivation and validation of a clinical risk score to predict death among patients awaiting cardiac surgery in Ontario, Canada: a population-based study.

BACKGROUND: Surgical delay may result in unintended harm to patients needing cardiac surgery, who are at risk for death if their condition is left untreated. Our objective was to derive and internally validate a clinical risk score to predict death among patients awaiting major cardiac surgery. METHODS: We used the CorHealth Ontario Registry and linked ICES health administrative databases with information on all Ontario residents to identify patients aged 18 years or more who were referred for isolated coronary artery bypass grafting (CABG), valvular procedures, combined CABG-valvular procedures or thoracic aorta procedures between Oct. 1, 2008, and Sept. 30, 2019. We used a hybrid modelling approach with the random forest method for initial variable selection, followed by backward stepwise logistic regression modelling for clinical interpretability and parsimony. We internally validated the logistic regression model, termed the CardiOttawa Waitlist Mortality Score, using 200 bootstraps. RESULTS: Of the 112 266 patients referred for cardiac surgery, 269 (0.2%) died while awaiting surgery (118/72 366 [0.2%] isolated CABG, 81/24 461 [0.3%] valvular procedures, 63/12 046 [0.5%] combined CABG-valvular procedures and 7/3393 [0.2%] thoracic aorta procedures). Age, sex, surgery type, left main stenosis, Canadian Cardiovascular Society classification, left ventricular ejection fraction, heart failure, atrial fibrillation, dialysis, psychosis and operative priority were predictors of waitlist mortality. The model discriminated (C-statistic 0.76 [optimism-corrected 0.73]). It calibrated well in the overall cohort (Hosmer-Lemeshow p = 0.2) and across surgery types. INTERPRETATION: The CardiOttawa Waitlist Mortality Score is a simple clinical risk model that predicts the likelihood of death while awaiting cardiac surgery. It has the potential to provide data-driven decision support for managing access to cardiac care and preserve system capacity during the COVID-19 pandemic, the recovery period and beyond.

Factors associated with SARS-CoV-2 test positivity in long-term care homes: A population-based cohort analysis using machine learning.

BACKGROUND: SARS-Cov-2 infection rates are high among residents of long-term care (LTC) homes. We used machine learning to identify resident and community characteristics predictive of SARS-Cov-2 infection. METHODS: We linked 26 population-based health and administrative databases to identify the population of all LTC residents tested for SARS-Cov-2 infection in Ontario, Canada. Using ensemble-based algorithms, we examined 484 factors, including individual-level demographics, healthcare use, comorbidities, functional status, and laboratory results; and community-level characteristics to identify factors predictive of infection. Analyses were performed separately for January to April (early wave 1) and May to August (late wave 1). FINDINGS: Among 80,784 LTC residents, 64,757 (80.2%) were tested for SARS-Cov-2 (median age 86 (78-91) years, 30.6% male), of whom 10.2% of 33,519 and 5.2% of 31,238 tested positive in early and late wave 1, respectively. In the late phase (when restriction of visitors, closure of communal spaces, and universal masking in LTC were routine), regional-level characteristics comprised 33 of the top 50 factors associated with testing positive, while laboratory values and comorbidities were also predictive. The c-index of the final model was 0.934, and sensitivity was 0.887. In the highest versus lowest risk quartiles, the odds ratio for infection was 114.3 (95% CI 38.6-557.3). LTC-related geographic variations existed in the distribution of observed infection rates and the proportion of residents at highest risk. INTERPRETATION: Machine learning informed evaluation of predicted and observed risks of SARS-CoV-2 infection at the resident and LTC levels, and may inform initiatives to improve care quality in this setting. FUNDING: Funded by a Canadian Institutes of Health Research, COVID-19 Rapid Research Funding Opportunity grant (# VR4 172736) and a Peter Munk Cardiac Centre Innovation Grant. Dr. D. Lee is the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto. Dr. Austin is supported by a Mid-Career investigator award from the Heart and Stroke Foundation. Dr. McAlister is supported by an Alberta Health Services Chair in Cardiovascular Outcomes Research. Dr. Kaul is the CIHR Sex and Gender Science Chair and the Heart & Stroke Chair in Cardiovascular Research. Dr. Rochon holds the RTO/ERO Chair in Geriatric Medicine from the University of Toronto. Dr. B. Wang holds a CIFAR AI chair at the Vector Institute.

A Population-Based Analysis of Diabetes-Related Care Measures, Foot Complications, and Amputation During the COVID-19 Pandemic in Ontario, Canada.

Importance: Deferred diabetic foot screening and delays in timely care of acute foot complications during the COVID-19 pandemic may have contributed to an increase in limb loss. Objective: To evaluate the association of the COVID-19 pandemic with diabetes-related care measures, foot complications, and amputation. Design, Setting, and Participants: This population-based cohort study included all adult residents of Ontario, Canada, with diabetes and compared the rates of selected outcomes from January 1, 2020, to February 23, 2021, vs January 1, 2019, to February 23, 2020. Main Outcomes and Measures: Comprehensive in-person diabetes care assessment, including foot examination; hemoglobin A1c (HbA1c) measurement; emergency department visit or hospitalization for diabetic foot ulceration, osteomyelitis, or gangrene; lower extremity open or endovascular revascularization; minor (toe or partial-foot) amputation; and major (above-ankle) leg amputation. Rates and rate ratios (RRs) comparing 2020-2021 vs 2019-2020 for each measure were calculated for 10-week periods, anchored relative to onset of the pandemic on March 11, 2020 (11th week of 2020). Results: On March 11, 2020, the study included 1 488 605 adults with diabetes (median [IQR] age, 65 [55-74] years; 776 665 [52.2%] men), and on March 11, 2019, the study included 1 441 029 adults with diabetes (median [IQR] age, 65 [55-74] years; 751 459 [52.1%] men). After the onset of the pandemic, rates of major amputation in 2020-2021 decreased compared with 2019-2020 levels. The RR for the prepandemic period from January 1 to March 10 was 1.05 (95% CI, 0.88-1.25), with RRs in the pandemic periods ranging from 0.86 (95% CI, 0.72-1.03) in May 20 to July 28 to 0.95 (95% CI, 0.80-1.13) in October 7 to December 15. There were no consistent differences in demographic characteristics or comorbidities of patients undergoing amputation in the 2020-2021 vs 2019-2020 periods. Rates of comprehensive in-person diabetes care assessment and HbA1c measurement declined sharply and remained below 2019-2020 levels (eg, in-person assessment, March 11 to May 19: RR, 0.28; 95% CI, 0.28-0.28). The rates of emergency department visits (eg, March 11 to May 19: RR, 0.67; 95% CI, 0.61-0.75), hospitalization (eg, March 11 to May 19: RR, 0.77; 95% CI, 0.68-0.87), open revascularization (eg, March 11 to May 19: RR, 0.66; 95% CI, 0.56-0.79), endovascular revascularization (March 11 to May 19: RR, 0.70; 95% CI, 0.61-0.81), and minor amputation (March 11 to May 19: RR, 0.70; 95% CI, 0.60-0.83) initially dropped but recovered to 2019-2020 levels over the study period. Conclusions and Relevance: In this population-based cohort study, disruptions in care related to the COVID-19 pandemic were not associated with excess leg amputations among people living with diabetes. As the pandemic ends, improved prevention and treatment of diabetic foot complications will be necessary to maintain these positive results.

The association between anticoagulation and adverse outcomes after a positive SARS-CoV-2 test among older outpatients: A population-based cohort study.

INTRODUCTION: Anticoagulation may improve outcomes in patients with COVID-19 when started early in the course of illness. MATERIALS AND METHODS: This was a population-based cohort study using linked administrative datasets of outpatients aged ≥65 years old testing positive for SARS-CoV-2 between January 1 and December 31, 2020 in Ontario, Canada. The key exposure was anticoagulation with warfarin or direct oral anticoagulants before COVID-19 diagnosis. We calculated propensity scores and used matching weights (MWs) to reduce baseline differences between anticoagulated and non-anticoagulated patients. The primary outcome was a composite of death or hospitalization within 60 days of a positive SARS-CoV-2 test. We used the Kaplan-Meier method and cumulative incidence functions to estimate risk of the primary and component outcomes at 60 days. RESULTS: We studied 23,159 outpatients (mean age 78.5 years; 13,474 [58.2%] female), among whom 3200 (13.8%) deaths and 3183 (13.7%) hospitalizations occurred within 60 days of the SARS-CoV-2 test. After application of MWs, the 60-day risk of death or hospitalization was 29.2% (95% CI 27.4%-31.2%) for anticoagulated individuals and 32.1% (95% CI 30.7%-33.5%) without anticoagulation (absolute risk difference [ARD], -2.9%; p = 0.005). Anticoagulation was also associated with a lower risk of death: 18.6% (95% CI 17.0%-20.2%) with anticoagulation and 20.9% (95% CI 19.7%-22.2%) in non-anticoagulated patients (ARD -2.3%; p = 0.005). CONCLUSIONS: Among outpatients aged ≥65 years, oral anticoagulation at the time of a positive SARS-CoV-2 test was associated with a lower risk of a composite of death or hospitalization within 60 days.

Statins and SARS-CoV-2 Infection: Results of a Population-Based Prospective Cohort Study of 469 749 Adults From 2 Canadian Provinces.

Background Small observational studies have suggested that statin users have a lower risk of dying with COVID-19. We tested this hypothesis in a large, population-based cohort of adults in 2 of Canada's most populous provinces: Ontario and Alberta. Methods and Results We examined reverse transcriptase-polymerase chain reaction swab positivity rates for SARS-CoV-2 in adults using statins compared with nonusers. In patients with SARS-CoV-2 infection, we compared 30-day risk of all-cause emergency department visit, hospitalization, intensive care unit admission, or death in statin users versus nonusers, adjusting for baseline differences in demographics, clinical comorbidities, and prior health care use, as well as propensity for statin use. Between January and June 2020, 2.4% of 226 142 tested individuals aged 18 to 65 years, 2.7% of 88 387 people aged 66 to 75 years, and 4.1% of 154 950 people older than 75 years had a positive reverse transcriptase-polymerase chain reaction swab for SARS-CoV-2. Compared with 353 878 nonusers, the 115 871 statin users were more likely to test positive for SARS-CoV-2 (3.6% versus 2.8%, P<0.001), but this difference was not significant after adjustment for baseline differences and propensity for statin use in each age stratum (adjusted odds ratio 1.00 [95% CI, 0.88-1.14], 1.00 [0.91-1.09], and 1.06 [0.82-1.38], respectively). In individuals younger than 75 years with SARS-CoV-2 infection, statin users were more likely to visit an emergency department, be hospitalized, be admitted to the intensive care unit, or to die of any cause within 30 days of their positive swab result than nonusers, but none of these associations were significant after multivariable adjustment. In individuals older than 75 years with SARS-CoV-2, statin users were more likely to visit an emergency department (28.2% versus 17.9%, adjusted odds ratio 1.41 [1.23-1.61]) or be hospitalized (32.7% versus 21.9%, adjusted odds ratio 1.19 [1.05-1.36]), but were less likely to die (26.9% versus 31.3%, adjusted odds ratio 0.76 [0.67-0.86]) of any cause within 30 days of their positive swab result than nonusers. Conclusions Compared with statin nonusers, patients taking statins exhibit the same risk of testing positive for SARS-CoV-2 and those younger than 75 years exhibit similar outcomes within 30 days of a positive test. Patients older than 75 years with a positive SARS-CoV-2 test and who were taking statins had more emergency department visits and hospitalizations, but exhibited lower 30-day all-cause mortality risk.

Emergency Department Visits, Care, and Outcome After Stroke and Myocardial Infarction During the COVID-19 Pandemic Phases.

BACKGROUND: It is not known if initial reductions in hospitalization for stroke and myocardial infarction early during the coronavirus disease-2019 pandemic were followed by subsequent increases. We describe the rates of emergency department visits for stroke and myocardial infarction through the pandemic phases. METHODS: We used linked administrative data to compare the weekly age- and sex-standardized rates of visits for stroke and myocardial infarction in Ontario, Canada in the first 9 months of 2020 to the mean baseline rates (2015-2019) using rate ratios (RRs) and 95% confidence intervals (CIs). We compared care and outcomes by pandemic phases (pre-pandemic was January-March, lockdown was March-May, early reopening was May-July, and late reopening was July-September). RESULTS: We identified 15,682 visits in 2020 for ischemic stroke (59.2%; n = 9279), intracerebral hemorrhage (12.2%; n = 1912), or myocardial infarction (28.6%; n = 4491). The weekly rates for stroke visits in 2020 were lower during the lockdown and early reopening than at baseline (RR 0.76, 95% CI [0.66, 0.87] for the largest weekly decrease). The weekly rates for myocardial infarction visits were lower during the lockdown only (RR 0.61, 95% CI [0.46, 0.77] for the largest weekly decrease), and there was a compensatory increase in visits following reopening. Ischemic stroke 30-day mortality was increased during the lockdown phase (11.5% pre-coronavirus disease; 12.2% during lockdown; 9.2% during early reopening; and 10.6% during late reopening, P = 0.015). CONCLUSION: After an initial reduction in visits for stroke and myocardial infarction, there was a compensatory increase in visits for myocardial infarction. The death rate after ischemic stroke was higher during the lockdown than in other phases.

CONTEXTE: Nous ignorons si les réductions des taux d'hospitalisations pour un AVC et un infarctus du myocarde observées au début de la pandémie de coronavirus de 2019 ont été suivies d'une hausse de ces taux. Nous décrivons ici les taux de visites aux services des urgences pour un AVC et un infarctus du myocarde pendant toutes les phases de la pandémie. MÉTHODES: À partir de données administratives couplées, nous comparons les taux hebdomadaires de visites pour un AVC et un infarctus du myocarde, normalisés en fonction de l'âge et du sexe, en Ontario, au Canada, effectuées pendant les neuf premiers mois de 2020, avec les taux moyens de base (2015-2019), en utilisant des ratios des taux (RR) et des intervalles de confiance (IC) à 95 %. Nous avons comparé les soins et les issues selon les phases de la pandémie (avant la pandémie : de janvier à mars; confinement : de mars à mai; début de la réouverture : de mai à juillet; phase tardive de la réouverture : de juillet à septembre). RÉSULTATS: Nous avons répertorié 15 682 visites effectuées en 2020 pour un AVC ischémique (59,2 %; n = 9 279), une hémorragie intracérébrale (12,2 %; n = 1 912) ou un infarctus du myocarde (28,6 %; n = 4 491). Les taux hebdomadaires de visites pour un AVC effectuées en 2020 étaient inférieurs pendant la période de confinement et le début de la réouverture comparativement à la période de base (RR : 0,76; IC à 95 % : 0,66-0,87 pour la plus grande baisse hebdomadaire). Les taux hebdomadaires de visites pour un infarctus du myocarde étaient inférieurs pendant la période de confinement seulement (RR : 0,61; IC à 95 % : 0,46-0,77 pour la baisse hebdomadaire la plus importante); une hausse compensatrice du nombre de visites a été notée après la réouverture. Le taux de mortalité à 30 jours des suites d'un AVC ischémique était plus élevé pendant la période de confinement (11,5 % avant la pandémie de coronavirus; 12,2 % pendant le confinement; 9,2 % au début de la période de réouverture; 10,6 % pendant la phase tardive de la réouverture, p = 0,015). CONCLUSION: Après une réduction initiale du nombre de visites motivées par un AVC et un infarctus du myocarde, on a noté une hausse compensatrice du nombre de visites motivées par un infarctus du myocarde. Le taux de mortalité des suites d'un AVC ischémique était plus élevé pendant la période de confinement que pendant les autres périodes.

Predictors of mortality among long-term care residents with SARS-CoV-2 infection.

BACKGROUND: While individuals living in long-term care (LTC) homes have experienced adverse outcomes of SARS-CoV-2 infection, few studies have examined a broad range of predictors of 30-day mortality in this population. METHODS: We studied residents living in LTC homes in Ontario, Canada, who underwent PCR testing for SARS-CoV-2 infection from January 1 to August 31, 2020, and examined predictors of all-cause death within 30 days after a positive test for SARS-CoV-2. We examined a broad range of risk factor categories including demographics, comorbidities, functional status, laboratory tests, and characteristics of the LTC facility and surrounding community were examined. In total, 304 potential predictors were evaluated for their association with mortality using machine learning (Random Forest). RESULTS: A total of 64,733 residents of LTC, median age 86 (78, 91) years (31.8% men), underwent SARS-CoV-2 testing, of whom 5029 (7.8%) tested positive. Thirty-day mortality rates were 28.7% (1442 deaths) after a positive test. Of 59,702 residents who tested negative, 2652 (4.4%) died within 30 days of testing. Predictors of mortality after SARS-CoV-2 infection included age, functional status (e.g., activity of daily living score and pressure ulcer risk), male sex, undernutrition, dehydration risk, prior hospital contacts for respiratory illness, and duration of comorbidities (e.g., heart failure, COPD). Lower GFR, hemoglobin concentration, lymphocyte count, and serum albumin were associated with higher mortality. After combining all covariates to generate a risk index, mortality rate in the highest risk quartile was 48.3% compared with 7% in the first quartile (odds ratio 12.42, 95%CI: 6.67, 22.80, p < 0.001). Deaths continued to increase rapidly for 15 days after the positive test. CONCLUSIONS: LTC residents, particularly those with reduced functional status, comorbidities, and abnormalities on routine laboratory tests, are at high risk for mortality after SARS-CoV-2 infection. Recognizing high-risk residents in LTC may enhance institution of appropriate preventative measures.

Rate of COVID-19 Infection in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The incidence of coronavirus disease 2019 (COVID-19) in patients with ST-segment elevation myocardial infarction (STEMI) has not been fully described. METHODS: All patients with STEMI undergoing primary percutaneous coronary intervention (PCI) in Ontario, Canada between March 1 and September 30, 2020 were included. Rates of positive COVID-19 tests from January 1, 2020 to the date of STEMI presentation were ascertained. For comparison, COVID-19 results were also evaluated in the adult Ontario population between January 1, 2020 and September 30, 2020, using provincial laboratory testing data. RESULTS: There were 3606 unique patients presenting with STEMI and receiving PCI in Ontario, Canada during the study period. Sixteen patients (0.44%) tested positive for COVID-19. The background infection rate among all 12,448,541 Ontario residents was similar, at 0.34%. CONCLUSIONS: The results of this population-based analysis suggest that proceeding with primary PCI with appropriate infection control practices is reasonable when community infection rates are low.

CONTEXTE: L'incidence de la maladie à coronavirus 2019 (COVID-19) chez les patients présentant un infarctus du myocarde avec élévation du segment ST (STEMI) n'a pas été entièrement décrite. MÉTHODOLOGIE: Tous les patients atteints de STEMI ayant subi une intervention coronarienne percutanée (ICP) primaire en Ontario (Canada) entre le 1er mars et le 30 septembre 2020 ont été inclus. Les taux de tests positifs à la COVID entre le 1er janvier 2020 et le moment de la présentation du STEMI ont été vérifiés. Aux fins de comparaison, les résultats des tests de dépistage de la COVID-19 ont également été évalués au sein de la population adulte de l'Ontario entre le 1er janvier 2020 et le 30 septembre 2020 au moyen des données des laboratoires provinciaux. RÉSULTATS: Pendant la période d'étude, 3 606 patients présentant un STEMI et ayant subi une ICP en Ontario (Canada) ont été recensés. Seize patients (0,44 %) ont reçu un résultat positif au test de dépistage de la COVID-19. Le taux d'infection parmi les 12 448 541 résidents de l'Ontario était similaire, soit 0,34 %. CONCLUSIONS: Les résultats de cette analyse populationnelle portent à penser qu'il est raisonnable de procéder à une ICP primaire avec des mesures appropriées de contrôle des infections lorsque les taux d'infection dans la collectivité sont faibles.

Reduced Rate of Hospital Presentations for Heart Failure During the COVID-19 Pandemic in Toronto, Canada.

Coronavirus disease 2019 (COVID-19) has resulted in public health measures and health care reconfigurations likely to have impact on chronic disease care. We aimed to assess the volume and characteristics of patients presenting to hospitals with acute decompensated heart failure (ADHF) during the 2020 COVID-19 pandemic compared with a time-matched 2019 cohort. Patients presenting to hospitals with ADHF from March 1, to April 19, 2020 and 2019 in an urban hospital were examined. Multivariable logistic-regression models were used to evaluate the difference in probability of ADHF-related hospitalization between the 2 years. During the COVID-19 pandemic, a total of 1106 emergency department (ED) visits for dyspnea or peripheral edema were recorded, compared with 800 ED visits in 2019. A decrease in ADHF-related ED visits of 43.5% (14.8%-79.4%, P = 0.002) and ADHF-related admissions of 39.3% (8.6%-78.5%, P = 0.009) was observed compared with 2019. Patients with ADHF presenting to hospitals (n = 128) were similar in age, sex, and comorbidities compared with the 2019 cohort (n = 186); however, a higher proportion had recent diagnoses of heart failure. Upon ED presentation, the relative probability of hospitalization or admission to intensive care was not statistically different. There was a trend toward higher in-hospital mortality in 2020. The decline in ADHF-related hospitalizations raises the timely question of how patients with heart failure are managing beyond the acute-care setting and reinforces the need for public education on the availability and safety of emergency services throughout the COVID-19 pandemic.