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.

Association Between Vaccination Status and Outcomes in Patients Admitted to the ICU With COVID-19.

OBJECTIVES: Although COVID-19 vaccines can reduce the need for intensive care unit admission in COVID-19, their effect on outcomes in critical illness remains unclear. We evaluated outcomes in vaccinated patients admitted to the ICU with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the association between vaccination and booster status on clinical outcomes. DESIGN: Retrospective cohort. SETTING AND PATIENTS: All patients were admitted to an ICU between January 2021 (after vaccination was available) and July 2022 with a diagnosis of COVID-19 based on a SARS-CoV-2 polymerase chain reaction test in Alberta, Canada. INTERVENTIONS: None. MEASUREMENT: The propensity-matched primary outcome of all-cause in-hospital mortality was compared between vaccinated and unvaccinated patients, and vaccinated patients were stratified by booster dosing. Secondary outcomes were mechanical ventilation (MV) duration ICU length of stay (LOS). MAIN RESULTS: The study included 3,293 patients: 743 (22.6%) were fully vaccinated (54.6% with booster), 166 (5.0%) were partially vaccinated, and 2,384 (72.4%) were unvaccinated. Unvaccinated patients were more likely to require invasive MV (78.4% vs 68.2%), vasopressor use (71.1% vs 66.6%), and extracorporeal membrane oxygenation (2.1% vs 0.5%). In a propensity-matched analysis, in-hospital mortality was similar (31.8% vs 34.0%, adjusted odds ratio [OR], 1.25; 95% CI, 0.97-1.61), but median duration MV (7.6 vs 4.7 d; p < 0.001) and ICU LOS (6.6 vs 5.2 d; p < 0.001) were longer in unvaccinated compared to fully vaccinated patients. Among vaccinated patients, greater than or equal to 1 booster had lower in-hospital mortality (25.5% vs 40.9%; adjusted OR, 0.50; 95% CI, 0.0.36-0.68) and duration of MV (3.8 vs 5.6 d; p = 0.025). CONCLUSIONS: Nearly one in four patients admitted to the ICU with COVID-19 after widespread COVID-19 vaccine availability represented a vaccine-breakthrough case. Mortality risk remains substantial in vaccinated patients and similar between vaccinated and unvaccinated patients after the onset of critical illness. However, COVID-19 vaccination is associated with reduced ICU resource utilization and booster dosing may increase survivability from COVID-19-related critical illness.

The burden of incidental SARS-CoV-2 infections in hospitalized patients across pandemic waves in Canada.

Many health authorities differentiate hospitalizations in patients infected with SARS-CoV-2 as being "for COVID-19" (due to direct manifestations of SARS-CoV-2 infection) versus being an "incidental" finding in someone admitted for an unrelated condition. We conducted a retrospective cohort study of all SARS-CoV-2 infected patients hospitalized via 47 Canadian emergency departments, March 2020-July 2022 to determine whether hospitalizations with "incidental" SARS-CoV-2 infection are less of a burden to patients and the healthcare system. Using a priori standardized definitions applied to hospital discharge diagnoses in 14,290 patients, we characterized COVID-19 as (i) the "Direct" cause for the hospitalization (70%), (ii) a potential "Contributing" factor for the hospitalization (4%), or (iii) an "Incidental" finding that did not influence the need for admission (26%). The proportion of incidental SARS-CoV-2 infections rose from 10% in Wave 1 to 41% during the Omicron wave. Patients with COVID-19 as the direct cause of hospitalization exhibited significantly longer LOS (mean 13.8 versus 12.1 days), were more likely to require critical care (22% versus 11%), receive COVID-19-specific therapies (55% versus 19%), and die (17% versus 9%) compared to patients with Incidental SARS-CoV-2 infections. However, patients hospitalized with incidental SARS-CoV-2 infection still exhibited substantial morbidity/mortality and hospital resource use.

Virtual care and emergency department use: CMAJ

Chami et al have clearly shown that the shift from predominantly in-person outpatient encounters to mixed models (with most visits being virtual) during the first year of the COVID-19 pandemic did not result in increased use of the emergency department (ED) by rostered patients of Ontario family physicians practicing in family health groups or family health organizations. Despite the robustness of their study, some questions remain unanswered. The generalizability of their findings outside of Ontario or for patients cared for by fee-for-service physicians is unclear. A recent study from Alberta of 33.7 million outpatient encounters between Mar 2019 and Mar 2021 can help fill this gap. They found that the COVID-19 pandemic did not negatively affect the frequency of outpatient follow-up or prescribing for community- dwelling adults with ambulatory care--sensitive conditions.

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.

Frequency and Type of Outpatient Visits for Patients With Cardiovascular Ambulatory-Care Sensitive Conditions During the COVID-19 Pandemic and Subsequent Outcomes: A Retrospective Cohort Study.

Background Because the impact of changes in how outpatient care was delivered during the COVID-19 pandemic is uncertain, we designed this study to examine the frequency and type of outpatient visits between March 1, 2019 to February 29, 2020 (prepandemic) and from March 1, 2020 to February 28, 2021 (pandemic) and specifically compared outcomes after virtual versus in-person outpatient visits during the pandemic. Methods and Results Population-based retrospective cohort study of all 3.8 million adults in Alberta, Canada. We examined all physician visits and 30- and 90-day outcomes, with a focus on those adults with the cardiovascular ambulatory-care sensitive conditions heart failure, hypertension, and diabetes. Our primary outcome was emergency department visit or hospitalization, evaluated using survival analysis accounting for competing risk of death. Although in-person outpatient visits decreased by 38.9% in the year after March 1, 2020 (10 142 184 versus 16 592 599 in the prior year), the introduction of virtual visits (7 152 147; 41.4% of total) meant that total outpatient visits increased by 4.1% in the first year of the pandemic for Albertan adults. Outpatient visit frequency (albeit 41.4% virtual, 58.6% in-person) and prescribing patterns were stable in the first year after pandemic onset for patients with the cardiovascular ambulatory-care sensitive conditions we examined, but laboratory test frequency declined by 20% (serum creatinine) to 47% (glycosylated hemoglobin). In the first year of the pandemic, virtual outpatient visits were associated with fewer subsequent emergency department visits or hospitalizations (compared with in-person visits) for patients with heart failure (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.85-0.96] at 30 days and 0.96 [95% CI, 0.92-1.00] at 90 days), hypertension (aHR, 0.88 [95% CI, 0.85-0.91] and 0.93 [95% CI, 0.91-0.95] at 30 and 90 days), or diabetes (aHR, 0.90 [95% CI, 0.87-0.93] and 0.93 [95% CI, 0.91-0.95] at 30 and 90 days). Conclusions The adoption and rapid uptake of virtual outpatient care during the COVID-19 pandemic did not negatively impact frequency of follow-up, prescribing, or short-term outcomes, and could have potentially positively impacted some of these for adults with heart failure, diabetes, or hypertension in a setting where there was an active reimbursement policy for virtual visits. Given declines in laboratory monitoring and screening activities, further research is needed to evaluate whether long-term outcomes will differ.

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.

Telemonitoring and protocolized case management for hypertensive community dwelling older adults (TECHNOMED): a randomized controlled trial.

BACKGROUND: Home blood pressure (BP) telemonitoring combined with case management leads to BP reductions in individuals with hypertension. However, its benefits are less clear in older (age ≥ 65 years) adults. METHODS: Twelve-month, open-label, randomized trial of community-dwelling older adults comparing the combination of home BP telemonitoring (HBPM) and pharmacist-led case management, vs. enhanced usual care with HBPM alone. The primary outcome was the proportion achieving systolic BP targets on 24-h ambulatory BP monitoring (ABPM). Changes in HBPM were also examined. Logistic and linear regressions were used for analyses, adjusted for baseline BP. RESULTS: Enrollment was stopped early due to coronavirus disease 2019. Participants randomized to intervention (n = 61) and control (n = 59) groups were mostly female (77%), with mean age 79.5 years. The adjusted odds ratio for ABPM BP target achievement was 1.48 (95% confidence interval 0.87-2.52, P = 0.15). At 12 months, the mean difference in BP changes between intervention and control groups was -1.6/-1.1 for ABPM (P-value 0.26 for systolic BP and 0.10 for diastolic BP), and -4.9/-3.1 for HBPM (P-value 0.04 for systolic BP and 0.01 for diastolic BP), favoring the intervention. Intervention group participants had hypotension (systolic BP < 110) more frequently (21% vs. 5%, P = 0.009), but no differences in orthostatic symptoms, syncope, non-mechanical falls, or emergency department visits. CONCLUSIONS: Home BP telemonitoring and pharmacist case management did not improve achievement of target range ambulatory BP, but did reduce home BP. It did not result in major adverse consequences.

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.

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.

Bedtime versus morning use of antihypertensives for cardiovascular risk reduction (BedMed): protocol for a prospective, randomised, open-label, blinded end-point pragmatic trial.

INTRODUCTION: Sleep-time blood pressure correlates more strongly with adverse cardiovascular events than does daytime blood pressure. The BedMed trial evaluates whether bedtime antihypertensive administration, as compared with conventional morning use, reduces major adverse cardiovascular events. METHODS AND ANALYSIS: DesignProspective randomised, open-label, blinded end-point trial.ParticipantsHypertensive primary care patients using blood pressure lowering medication and free from glaucoma.SettingCommunity primary care providers in 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario) are mailing invitations to their eligible patients. Social media campaigns (Google, Facebook) are additionally running in the same provinces.InterventionConsenting participants are allocated via central randomisation to bedtime vs morning use of all antihypertensives.Follow-up(1) Telephone or email questionnaire at 1 week, 6 weeks, 6 months and every 6 months thereafter, and (2) accessing linked governmental healthcare databases tracking hospital and community medical services.Primary outcomeComposite of all-cause death, or hospitalisation for myocardial infarction/acute-coronary syndrome, stroke or congestive heart failure.Secondary outcomesEach primary outcome element on its own, all-cause hospitalisation or emergency department visit, long-term care admission, non-vertebral fracture, new glaucoma diagnosis, 18-month cognitive decline from baseline (via Short Blessed Test).Select other outcomesSelf-reported nocturia burden at 6 weeks and 6 months (no, minor or major burden), 1-year self-reported overall health score (EQ-5D-5L), self-reported falls, total cost of care (acute and community over study duration) and mean sleep-time systolic blood pressure after 6 months (via 24-hour monitor in a subset of 302 sequential participants).Primary outcome analysisCox proportional hazards survival analysis.Sample sizeThe trial will continue until a projected 254 primary outcome events have occurred.Current statusEnrolment ongoing (3227 randomised to date). ETHICS AND DISSEMINATION: BedMed has ethics approval from six research ethics review boards and will publish results in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02990663.

Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial.

BACKGROUND: Dietary restriction of sodium has been suggested to prevent fluid overload and adverse outcomes for patients with heart failure. We designed the Study of Dietary Intervention under 100 mmol in Heart Failure (SODIUM-HF) to test whether or not a reduction in dietary sodium reduces the incidence of future clinical events. METHODS: SODIUM-HF is an international, open-label, randomised, controlled trial that enrolled patients at 26 sites in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand). Eligible patients were aged 18 years or older, with chronic heart failure (New York Heart Association [NYHA] functional class 2-3), and receiving optimally tolerated guideline-directed medical treatment. Patients were randomly assigned (1:1), using a standard number generator and varying block sizes of two, four, or six, stratified by site, to either usual care according to local guidelines or a low sodium diet of less than 100 mmol (ie, <1500 mg/day). The primary outcome was the composite of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death within 12 months in the intention-to-treat (ITT) population (ie, all randomly assigned patients). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT02012179, and is closed to accrual. FINDINGS: Between March 24, 2014, and Dec 9, 2020, 806 patients were randomly assigned to a low sodium diet (n=397) or usual care (n=409). Median age was 67 years (IQR 58-74) and 268 (33%) were women and 538 (66%) were men. Between baseline and 12 months, the median sodium intake decreased from 2286 mg/day (IQR 1653-3005) to 1658 mg/day (1301-2189) in the low sodium group and from 2119 mg/day (1673-2804) to 2073 mg/day (1541-2900) in the usual care group. By 12 months, events comprising the primary outcome had occurred in 60 (15%) of 397 patients in the low sodium diet group and 70 (17%) of 409 in the usual care group (hazard ratio [HR] 0·89 [95% CI 0·63-1·26]; p=0·53). All-cause death occurred in 22 (6%) patients in the low sodium diet group and 17 (4%) in the usual care group (HR 1·38 [0·73-2·60]; p=0·32), cardiovascular-related hospitalisation occurred in 40 (10%) patients in the low sodium diet group and 51 (12%) patients in the usual care group (HR 0·82 [0·54-1·24]; p=0·36), and cardiovascular-related emergency department visits occurred in 17 (4%) patients in the low sodium diet group and 15 (4%) patients in the usual care group (HR 1·21 [0·60-2·41]; p=0·60). No safety events related to the study treatment were reported in either group. INTERPRETATION: In ambulatory patients with heart failure, a dietary intervention to reduce sodium intake did not reduce clinical events. FUNDING: Canadian Institutes of Health Research and the University Hospital Foundation, Edmonton, Alberta, Canada, and Health Research Council of New Zealand.

Changes in ischemic stroke presentations, management and outcomes during the first year of the COVID-19 pandemic in Alberta: a population study.

BACKGROUND: Pandemics may promote hospital avoidance, and added precautions may exacerbate treatment delays for medical emergencies such as stroke. We sought to evaluate ischemic stroke presentations, management and outcomes during the first year of the COVID-19 pandemic. METHODS: We conducted a population-based study, using linked administrative and stroke registry data from Alberta to identify all patients presenting with stroke before the pandemic (Jan. 1, 2016 to Feb. 27, 2020) and in 5 periods over the first pandemic year (Feb. 28, 2020 to Mar. 31, 2021), reflecting changes in case numbers and restrictions. We evaluated changes in hospital admissions, emergency department presentations, thrombolysis, endovascular therapy, workflow times and outcomes. RESULTS: The study included 19 531 patients in the prepandemic period and 4900 patients across the 5 pandemic periods. Presentations for ischemic stroke dropped in the first pandemic wave (weekly adjusted incidence rate ratio [IRR] 0.54, 95% confidence interval [CI] 0.50 to 0.59). Population-level incidence of thrombolysis (adjusted IRR 0.50, 95% CI 0.41 to 0.62) and endovascular therapy (adjusted IRR 0.63, 95% CI 0.47 to 0.84) also decreased during the first wave, but proportions of patients presenting with stroke who received acute therapies did not decline. Rates of patients presenting with stroke did not return to prepandemic levels, even during a lull in COVID-19 cases between the first 2 waves of the pandemic, and fell further in subsequent waves. In-hospital delays in thrombolysis or endovascular therapy occurred in several pandemic periods. The likelihood of in-hospital death increased in Wave 2 (adjusted odds ratio [OR] 1.48, 95% CI 1.25 to 1.74) and Wave 3 (adjusted OR 1.46, 95% CI 1.07 to 2.00). Out-of-hospital deaths, as a proportion of stroke-related deaths, rose during 4 of 5 pandemic periods. INTERPRETATION: The first year of the COVID-19 pandemic saw persistently reduced rates of patients presenting with ischemic stroke, recurrent treatment delays and higher risk of in-hospital death in later waves. These findings support public health messaging that encourages care-seeking for medical emergencies during pandemic periods, and stroke systems should re-evaluate protocols to mitigate inefficiencies.

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.

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.

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.