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Background: Evidence on protection of different patterns of infection- and vaccine-acquired immunity against Omicron-associated severe illness is useful in planning booster vaccination strategies. We examined protection of prior SARS-CoV-2 infection, a third or a fourth COVID-19 vaccine dose, and hybrid immunity against Omicron-associated severe illness. Methods and findings: This population-based cohort study followed five million individuals with at least one SARS-CoV-2 RT-PCR test before November 21, 2021 until an Omicron-associatedhospitalization or death. We used Cox regression models to estimate risks of Omicron-associated hospitalization and a composite severe outcome (hospitalized and death), among individuals with infection- and/or vaccination-acquired immunity. Individuals who were unvaccinated and had no history of a prior infection severed as the reference group. Both adjusted hazard ratios (HR) and corresponding protection (one minus adjusted HR), with 95% confidence intervals (CIs), were reported. Three doses provided 94% (95%CI 93–95) and 93% (95%CI 91–94) protection against Omicron-associated hospitalization at 2–3 and ≥3 months post-vaccination respectively, similar to the protection conferred by three doses and a prior infection (2–3 months: 99%, 95%CI 97–100; ≥3 months: 97%, 95%CI 92–99) and four doses (1 month: 87%, 95%CI 79–92; 1–2 months: 96%, 95%CI 92–98). In individuals ≥65 years old, protection of four doses increased to 95% (95%CI 91–98) at 1–2 months, significantly higher than that of three doses over the follow-up period. Similar results were observed with the composite severe outcome. Conclusion: At least three antigenic exposures, achieved by vaccination or infection, confers significant protection against Omicron-associated hospitalization and death in all age groups. Our findings support a third dose for the overall population, regardless of prior infection status, and a fourth dose for the elderly to maintain high level of immunity and substantially reduce risk of severe illness at individual level. [ABSTRACT FROM AUTHOR]

• Previous SARS-CoV-2 infections confer added benefits in reducing Omicron reinfection risk. • The incremental immunity acquired from past infections waned within 1 year. • Infection-acquired immunity has limited influence on shield-effects at the population level. • This is one of the largest cohort studies to examine infection-acquired immunity. We examined the incremental protection and durability of infection-acquired immunity against Omicron infection in individuals with hybrid immunity in Ontario, Canada. We followed up 6 million individuals with at least one multiplex reverse transcriptase–polymerase chain reaction test before November 21, 2021, until an Omicron infection. Protection via infection-acquired immunity was assessed by comparing Omicron infection risk between previously infected individuals and those without documented infection under different vaccination scenarios and stratified by time since the last infection or vaccination. A previous infection was associated with 68% (95% CI 61-73) and 43% (95% CI 27-56) increased protection against Omicron infection in individuals with two and three doses, respectively. Among individuals with two-dose vaccination, the incremental protection of infection-induced immunity decreased from 79% (95% CI 75-81) within 3 months after vaccination or infection to 27% (95% CI 14-37) at 9-11 months. In individuals with three-dose vaccination, it decreased from 57% (95% CI 50-63) within 3 months to 37% (95% CI 19-51) at 3-5 months after vaccination or infection. Previous SARS-CovV-2 infections provide added cross-variant immunity to vaccination. Given the limited durability of infection-acquired protection in individuals with hybrid immunity, its influence on shield-effects at the population level and reinfection risks at the individual level may be limited. [ABSTRACT FROM AUTHOR]

This paper examines the positioning of gender within women-focused capital funds (WFCFs) to consider the extent to which these digitally enabled sources of finance reflect the tenets of entrepreneurial feminism. Content analysis of 27 funds situated in Canada and the USA informs about fund mandates, rationales, types of capital, and anticipated outcomes. Our findings reveal that a minority of WFCFs examined sought to enhance equity and counter structural barriers associated with women entrepreneurs' access to financial capital. Alternatively, the majority of WFCFs were positioned as vehicles to facilitate individual wealth creation. Eligibility ranged from multiple gender identities of the business owner to "women-led" businesses—defined as at least one woman executive, board or steering committee member. The latter of these criteria has the effect of diverting attention away from firms that are launched by women entrepreneurs. Pinkwashing was more likely to occur when WFCFs were created as add-ons to mainstream programs and services, rather than as a central element of the organization's mission of supporting women and non-binary femmes. The findings support arguments that technology can both challenge or reinforce structural constraints that impede women entrepreneurs in the digital era. [ABSTRACT FROM AUTHOR]

Introduction: Kidney transplantation is associated with increased risk of bone fracture. Current literature reports widely variable fracture burden and contains limited data on risk factors for recurrent fractures. Methods: The incidence of all and major osteoporotic fractures (hip, forearm, thoracolumbar, and proximal humerus) were assessed. The risk factors for first and recurrent fractures among 1285 Canadian kidney transplant recipients transplanted between January 1, 2004, and December 31, 2013 were also identified. Results: The 10-year cumulative incidence of all fractures and major osteoporotic fractures in this population was 27.1% (95% CI: 22.5, 32.4) and 17.8% (95% CI: 13.4, 23.5), respectively. On multivariable analysis, female sex (HR = 1.64 [95% CI: 1.20, 2.26]), history of fracture (HR = 1.54 [95% CI: 1.12, 2.11]), and pretransplant diabetes (HR = 1.85 [95% CI: 1.29, 2.65]) were recipient factors found to increase the risk for any first fracture posttransplant. These risk factors persist in analysis with the time origin 3-months posttransplant, where transplant age (HR = 1.01 [95% CI: 1.00, 1.03]) and increased time on pretransplant dialysis (HR = 1.06 [95% CI: 1.00, 1.12]) also emerge as risk factors for first fracture. On multivariable shared frailty model analysis, increased risk of recurrent fractures was associated with recipient female sex (HR = 1.74 [95% CI: 1.21, 2.51]) and history of diabetes (HR = 1.76 [95% CI: 1.17, 2.66]). Discussion: The results suggested that some risk factors for first fracture may not inform risk of recurrent fractures. As such, fracture risk should be assessed accordingly to optimize long-term care and implement preventive measures.

Background: The novel coronavirus disease 2019 (COVID-19) has infected 1.9% of the world population by May 2, 2021. Since most previous studies that examined risk factors for mortality and severity were based on hospitalized individuals, population-based cohort studies are called for to provide evidence that can be extrapolated to the general population. Therefore, we aimed to examine the associations of comorbidities with mortality and disease severity in individuals with COVID-19 diagnosed in 2020 in Ontario, Canada., Methods and Findings: We conducted a retrospective cohort study of all individuals with COVID-19 in Ontario, Canada diagnosed between January 15 and December 31, 2020. Cases were linked to health administrative databases maintained in the ICES which covers all residents in Ontario. The primary outcome is all-cause 30-day mortality after the first COVID-19 diagnosis, and the secondary outcome is a composite severity index containing death and hospitalization. To examine the risk factors for the outcomes, we employed Cox proportional hazards regression models and logistic regression models to adjust for demographic, socio-economic variables and comorbidities. Results were also stratified by age groups. A total of 167,500 individuals were diagnosed of COVID-19 in 2020 and included in the study. About half (43.8%, n = 73,378) had at least one comorbidity. The median follow-up period were 30 days. The most common comorbidities were hypertension (24%, n = 40,154), asthma (16%, n = 26,814), and diabetes (14.7%, n = 24,662). Individuals with comorbidity had higher risk of mortality compared to those without (HR = 2.80, 95%CI 2.35-3.34; p<0.001), and the risk substantially was elevated from 2.14 (95%CI 1.76-2.60) to 4.81 (95%CI 3.95-5.85) times as the number of comorbidities increased from one to five or more. Significant predictors for mortality included comorbidities such as solid organ transplant (HR = 3.06, 95%CI 2.03-4.63; p<0.001), dementia (HR = 1.46, 95%CI 1.35-1.58; p<0.001), chronic kidney disease (HR = 1.45, 95%CI 1.34-1.57; p<0.001), severe mental illness (HR = 1.42, 95%CI%, 1.12-1.80; p<0.001), cardiovascular disease (CVD) (HR = 1.22, 95%CI, 1.15-1.30), diabetes (HR = 1.19, 95%, 1.12-1.26; p<0.001), chronic obstructive pulmonary disease (COPD) (HR = 1.19, 95%CI 1.12-1.26; p<0.001), cancer (HR = 1.17, 95%CI, 1.09-1.27; p<0.001), hypertension (HR = 1.16, 95%CI, 1.07-1.26; p<0.001). Compared to their effect in older age groups, comorbidities were associated with higher risk of mortality and severity in individuals under 50 years old. Individuals with five or more comorbidities in the below 50 years age group had 395.44 (95%CI, 57.93-2699.44, p<0.001) times higher risk of mortality compared to those without. Limitations include that data were collected during 2020 when the new variants of concern were not predominant, and that the ICES databases do not contain detailed individual-level socioeconomic and racial variables., Conclusion: We found that solid organ transplant, dementia, chronic kidney disease, severe mental illness, CVD, hypertension, COPD, cancer, diabetes, rheumatoid arthritis, HIV, and asthma were associated with mortality or severity. Our study highlights that the number of comorbidities was a strong risk factor for deaths and severe outcomes among younger individuals with COVID-19. Our findings suggest that in addition of prioritizing by age, vaccination priority groups should also include younger population with multiple comorbidities., Competing Interests: The authors have declared that no competing interests exist.

Bacteremia is an important complication after kidney transplantation. We examined bacteremia and its outcomes in a large cohort of kidney transplant recipients. Kidney transplants from 1-Jul-2004 to 1-Dec-2014 at the Toronto General Hospital were eligible for study inclusion. Bacteremia was defined as two blood culture positives for common skin contaminants or one blood culture positive for other organisms. The cumulative incidence of first bacteremia was estimated using the Kaplan-Meier method, and risk factors were examined in a Cox proportional hazards model. The risk of graft failure or death was assessed in a time-dependent Cox model. Over follow-up, 154 of 1333 patients had at least one bacteremia episode. The cumulative incidence of first bacteremia was 6.8% (6 months) and 11.9% (5 years). Risk factors included recipient diabetes mellitus, time on dialysis, dialysis modality, delayed graft function, donor age, and donor eGFR. Bacteremia increased the risk of total graft failure (hazard ratio 2.11 [95% CI: 1.50, 2.96]), death-censored graft failure (1.73 [0.99, 3.02]), and death with graft function (2.52 [1.63, 3.89]). In conclusion, bacteremia is common after kidney transplantation and impacts both graft and patient survival. Identifying high-risk patients for targeted preventive strategies may reduce the burden and adverse consequences of this important complication., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context: An increasing demand for kidney transplantation has enticed some patients with end-stage renal disease (ESRD) to venture outside their country of residence, but their posttransplant outcomes may be suboptimal., Objective: We compared the risks and clinical outcomes among tourists, or patients who pursue a kidney transplant abroad, versus patients who received a transplant at the Toronto General Hospital (TGH)., Methods: A single-center, 1:3 matched (based on age at transplant, time on dialysis, and year of transplant) cohort study was conducted. Forty-five tourists were matched with 135 domestic transplant recipients between January 1, 2000, and December 31, 2011. Multivariable Cox proportional hazards models were fitted to assess graft and patient outcomes., Results: Among the 45 tourists, the majority (38 of 45) traveled to the Middle East or Far East Asia, and most received living donor kidney transplants (35 of 45). Multivariable Cox proportional hazards models showed that tourists had a higher risk for the composite outcome of acute rejection, death-censored graft failure, or death with graft function (DWGF; hazard ratio [HR] 2.08, 95% confidence interval [CI]: 1.06-4.07). Tourists also showed a higher risk for the individual end points of acute rejection, DWGF, and posttransplant hospitalizations., Conclusion: Patients going abroad for kidney transplantation may have inferior outcomes compared to domestic patients receiving kidney transplants. Patients who are contemplating an overseas transplant need to be aware of the increased risk of adverse posttransplant outcomes and should be appropriately counseled by transplant professionals during the pretransplant evaluation process., (© 2016, NATCO.)

Background: Prognostic models, such as the Seattle Heart Failure Model (SHFM), have been developed to predict patient survival. The extent to which they predict medical resource use and costs has not been explored. In this study, we evaluated relationships between baseline SHFM scores and 1-year resource use and costs using data from a clinical trial., Methods and Results: We applied generalized linear models to examine the relative impact of a 1-unit increase in SHFM scores on counts of medical resource use and direct medical costs at 1 year of follow-up. Of 2331 randomized patients, 2288 (98%) had a rounded integer SHFM score between -1 and 2, consistent with predicted 1-year survival of 98% and 74%, respectively. At baseline, median age was 59 years, 28% of patients were women, and nearly two-thirds of the cohort had New York Heart Association class II heart failure and one-third had class III heart failure. Higher SHFM scores were associated with more hospitalizations (rate ratio per 1-unit increase, 1.86; P < .001), more inpatient days (2.30; P < .001), and higher inpatient costs (2.28; P < .001), outpatient costs (1.54; P < .001), and total medical costs (2.13; P < .001)., Conclusion: Although developed to predict all-cause mortality, SHFM scores also predict medical resource use and costs., (Copyright © 2014 Elsevier Inc. All rights reserved.)