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Background. The 2014–2015 influenza season was distinguished by an epidemic of antigenically-drifted A(H3N2) viruses and vaccine components identical to 2013–2014. We report 2014–2015 vaccine effectiveness (VE) from Canada and explore contributing agent–host factors. Methods. VE against laboratory-confirmed influenza was derived using a test-negative design among outpatients with influenza-like illness. Sequencing identified amino acid mutations at key antigenic sites of the viral hemagglutinin protein. Results. Overall, 815/1930 (42%) patients tested influenza-positive: 590 (72%) influenza A and 226 (28%) influenza B. Most influenza A viruses with known subtype were A(H3N2) (570/577; 99%); 409/460 (89%) sequenced viruses belonged to genetic clade 3C.2a and 39/460 (8%) to clade 3C.3b. Dominant clade 3C.2a viruses bore the pivotal mutations F159Y (a cluster-transition position) and K160T (a predicted gain of glycosylation) compared to the mismatched clade 3C.1 vaccine. VE against A(H3N2) was −17% (95% confidence interval [CI], −50% to 9%) overall with clade-specific VE of −13% (95% CI, −51% to 15%) for clade 3C.2a but 52% (95% CI, −17% to 80%) for clade 3C.3b. VE against A(H3N2) was 53% (95% CI, 10% to 75%) for patients vaccinated in 2014–2015 only, significantly lower at −32% (95% CI, −75% to 0%) if also vaccinated in 2013–2014 and −54% (95% CI, −108% to −14%) if vaccinated each year since 2012–2013. VE against clade-mismatched B(Yamagata) viruses was 42% (95% CI, 10% to 62%) with less-pronounced reduction from prior vaccination compared to A(H3N2). Conclusions. Variation in the viral genome and negative effects of serial vaccination likely contributed to poor influenza vaccine performance in 2014–2015.

Background. The antigenic distance hypothesis (ADH) predicts that negative interference from prior season's influenza vaccine (v1) on the current season's vaccine (v2) protection may occur when the antigenic distance is small between v1 and v2 (v1 ≈ v2) but large between v1 and the current epidemic (e) strain (v1 ≠ e). Methods. Vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza A(H3N2) illness was estimated by test-negative design during 3 A(H3N2) epidemics (2010–2011, 2012–2013, 2014–2015) in Canada. Vaccine effectiveness was derived with covariate adjustment across v2 and/or v1 categories relative to no vaccine receipt among outpatients aged ≥9 years. Prior vaccination effects were interpreted within the ADH framework. Results. Prior vaccination effects varied significantly by season, consistent with the ADH. There was no interference by v1 in 2010–2011 when v1 ≠ v2 and v1 ≠ e, with comparable VE for v2 alone or v2 + v1: 34% (95% confidence interval [CI] = −51% to 71%) versus 34% (95% CI = −5% to 58%). Negative interference by v1 was suggested in 2012–2013 with nonsignificant reduction in VE when v1 ≈ v2 and v1 ≠ e: 49% (95% CI = −47% to 83%) versus 28% (95% CI = −12% to 54%). Negative effects of prior vaccination were pronounced and statistically significant in 2014–2015 when v1 ≡ v2 and v1 ≠ e: 65% (95% CI = 25% to 83%) versus −33% (95% CI = −78% to 1%). Conclusions. Effects of repeat influenza vaccination were consistent with the ADH and may have contributed to findings of low VE across recent A(H3N2) epidemics since 2010 in Canada.

Objectives. We identified predictors of emergency department (ED) use among a population-based prospective cohort of homeless adults in Toronto, Ontario. Methods. We assessed ED visit rates using administrative data from the Institute for Clinical Evaluative Sciences (2005–2009). We then used logistic regression to identify predictors of ED use. Frequent users were defined as participants with rates in the top decile (≥ 4.7 visits per person-year). Results. Among 1165 homeless adults, 892 (77%) had at least 1 ED visit during the study. The average rate of ED visits was 2.0 visits per person-year, whereas frequent users averaged 12.1 visits per person-year. Frequent users accounted for 10% of the sample but contributed more than 60% of visits. Predictors of frequent use in adjusted analyses included birth in Canada, higher monthly income, lower health status, perceived unmet mental health needs, and perceived external health locus of control from powerful others; being accompanied by a partner or dependent children had a protective effect on frequent use. Conclusions. Among homeless adults with universal health insurance, a small subgroup accounted for the majority of visits to emergency services. Frequent use was driven by multiple predisposing, enabling, and need factors.

Foreign-born children may face greater barriers to accessing routine immunizations in Canada or their country of birth, but provincial surveillance data on immigration status are lacking. Using our provincial immunization repository linked to administrative data, we assessed immunization coverage among immigrant and refugee children in Ontario, Canada, compared with Ontario-born children and identified factors associated with being up-to-date (UTD). We conducted a retrospective cohort study of children entering school during the 2012/13-2014/15 school years. We calculated UTD coverage for measles (2 doses), diphtheria (4 doses), and polio (3 doses) vaccines at school entry and two years after school attendance. We compared UTD coverage between immigrant/refugee children and Ontario-born children using standardized differences (SD). In a cohort of 363,662 children, 15,114 (4.2%) were immigrants/refugees (82.1% immigrants, 17.9% refugees). UTD coverage for all antigens combined was 59.2% among immigrant/refugee children compared with 87.9% among Ontario-born children at school entry (SD = 0.69), increasing to 84.9% and 94.3%, respectively, two years after school entry (SD = 0.31). Coverage was lower with greater disparities between immigrant/refugee and Ontario-born children for measles (87.9% vs. 94.8%, SD = 0.25) and diphtheria (94.6% vs. 97.4%, SD = 0.15) after two years than polio (97.1% vs. 98.4%, SD = 0.09). Among immigrant/refugee children, coverage was lowest in refugees (vs. immigrants), recent immigrants, and those born in certain regions. Immunization coverage among foreign-born children lagged behind their Ontario-born peers, even after two years of school attendance. Findings varied by vaccine, immigration category, time spent in Ontario, and country of birth.

Background. Canada's Sentinel Physician Surveillance Network links genetic, antigenic, and vaccine effectiveness (VE) measures in an integrated platform of influenza monitoring, described here for the 2013-2014 influenza season of resurgent A(H1N1)pdm09 and late-season type B activity. Methods. VE was estimated as [1 — odds ratio] × 100% and compared vaccination status between individuals who tested positive (cases) and those who tested negative (controls) for influenza virus. Vaccine-virus relatedness was assessed by genomic sequence analysis and hemagglutination inhibition assays. Results. Analyses included 1037 controls (of whom 33% were vaccinated) and 663 cases (of whom 14% were vaccinated). A total of 415 cases tested positive for A(H1N1)pdm09 virus, 15 tested positive for A(H3N2) virus, 191 tested positive for B/Yamagata-lineage virus, 6 tested positive for B/Victoria-lineage virus, and 36 tested positive for viruses of unknown subtype or lineage. A(H1N1)pdm09 viruses belonged to clade 6B, distinguished by a K163Q substitution, but remained antigenically similar to the A/California/07/2009-like vaccine strain, with an adjusted VE of 71% (95% confidence interval [CI], 58%-80%). Most B/Yamagata-lineage viruses (83%) clustered phylogenetically with the prior (ie, 2012-2013) season's B/Wisconsin/01/2010-like clade 3 vaccine strain, while only 17% clustered with the current (ie, 2013-2014) season's B/Massachusetts/02/2012-like clade 2 vaccine strain. The adjusted VE for B/Yamagata-lineage virus was 73% (95% CI, 57%-84%), with a lower VE obtained after partial calendar-time adjustment for clade-mismatched B/Wisconsin/01/2010-like virus (VE, 63%; 95% CI, 41%-77%), compared with that for clade-matched B/Massachusetts/02/2012-like virus (VE, 88%; 95% CI, 48%-97%). No A(H3N2) viruses clustered with the A/Texas/50/2012-like clade 3C.1 vaccine strain, and more than half were antigenically mismatched, but sparse data did not support VE estimation. Conclusions. VE corresponded with antigenically conserved A(HIN1)pdm09 and lineage-matched B/Yamagata viruses with clade-level variation. Surveillance linking genotypic, phenotypic, and epidemiologie measures of vaccine-virus relatedness and effectiveness could better inform predictions of vaccine performance and reformulation.

Although clinical trials are necessary for vaccine approval, observational epidemiology will be required to evaluate the long-term effectiveness, safety, and population impacts of newly approved COVID-19 vaccines under real-world field conditions. In this commentary, I argue that a hybrid approach that combines new data sources and tools, including COVID-19 vaccine registries, with traditional epidemiological methods will be needed to evaluate COVID-19 vaccines using observational epidemiology. Wherever possible, primary data collection, active surveillance, and linkage with existing population-based cohorts should be leveraged to supplement secondary data sources and passive surveillance systems. Evidence-informed public health decision making around provincial COVID-19 immunization programs will need to account for potential biases, incomplete or conflicting information, and heterogeneity across subpopulations. Des essais cliniques sont nécessaires à l’approbation des vaccins, mais il faudra recourir à l’épidémiologie d’observation pour évaluer en conditions réelles de terrain l’efficacité à long terme, l’innocuité et les effets sur les populations des vaccins contre la COVID-19 nouvellement approuvés. Dans ce commentaire, je fais valoir qu’il faudra adopter une démarche hybride combinant de nouvelles sources de données et de nouveaux outils, dont les registres de vaccins anti-COVID-19, et des méthodes épidémiologiques classiques pour évaluer les vaccins anti-COVID-19 à l’aide de l’épidémiologie d’observation. Dans la mesure du possible, il faudra utiliser la collecte de données primaires, la surveillance active et les maillages avec les cohortes populationnelles existantes pour compléter les sources de données secondaires et les systèmes de surveillance passive. Les décisions de santé publique éclairées par les données probantes sur les programmes d’immunisation provinciaux contre la COVID-19 devront tenir compte des biais possibles, des informations incomplètes ou contradictoires et de l’hétérogénéité des sous-populations.

Introduction: People living with HIV (PLWH) and/or who inject drugs may experience lower vaccine effectiveness (VE) against SARS‐CoV‐2 infection. Methods: A validated algorithm was applied to population‐based, linked administrative datasets in the British Columbia COVID‐19 Cohort (BCC19C) to ascertain HIV status and create a population of PLWH and matched HIV‐negative individuals. The study population was limited to individuals who received an RT‐PCR laboratory test for SARS‐CoV‐2 between 15 December 2020 and 21 November 2021 in BC, Canada. Any history of injection drug use (IDU) was ascertained using a validated administrative algorithm. We used a test‐negative study design (modified case−control analysis) and multivariable logistic regression to estimate adjusted VE by HIV status and history of IDU. Results: Our analysis included 2700 PLWH and a matched population of 375,043 HIV‐negative individuals, among whom there were 351 and 103,049 SARS‐CoV‐2 cases, respectively. The proportion of people with IDU history was much higher among PLWH compared to HIV‐negative individuals (40.7% vs. 4.3%). Overall VE during the first 6 months after second dose was lower among PLWH with IDU history (65.8%, 95% CI = 43.5–79.3) than PLWH with no IDU history (80.3%, 95% CI = 62.7–89.6), and VE was particularly low at 4–6 months (42.4%, 95% CI = −17.8 to 71.8 with IDU history vs. 64.0%; 95% CI = 15.7–84.7 without), although confidence intervals were wide. In contrast, overall VE was 88.6% (95% CI = 88.2–89.0) in the matched HIV‐negative population with no history of IDU and remained relatively high at 4–6 months after second dose (84.6%, 95% CI = 83.8–85.4). Despite different patterns of vaccine protection by HIV status and IDU history, peak estimates were similar (≥88%) across all populations. Conclusions: PLWH with a history of IDU may experience lower VE against COVID‐19 infection, although findings were limited by a small sample size. The lower VE at 4–6 months may have implications for booster dose prioritization for PLWH and people who inject drugs. The immunocompromising effect of HIV, substance use and/or co‐occurring comorbidities may partly explain these findings.

COVID-19 breakthrough infection (BTI) can occur despite vaccination. Using a multi-centre, prospective, observational Canadian cohort of people with HIV (PWH) receiving ≥2 COVID-19 vaccines, we compared the SARS-CoV-2 spike (S) and receptor-binding domain (RBD)-specific IgG levels 3 and 6 months post second dose, as well as 1 month post third dose, in PWH with and without BTI. BTI was defined as positivity based on self-report measures (data up to last study visit) or IgG data (up to 1 month post dose 3). The self-report measures were based on their symptoms and either a positive PCR or rapid antigen test. The analysis was restricted to persons without previous COVID-19 infection. Persons without BTI remained COVID-19-naïve until ≥3 months following the third dose. Of 289 participants, 92 developed BTI (31.5 infections per 100 person-years). The median days between last vaccination and BTI was 128 (IQR 67, 176), with the most cases occurring between the third and fourth dose (n = 59), corresponding to the Omicron wave. In analyses adjusted for age, sex, race, multimorbidity, hypertension, chronic kidney disease, diabetes and obesity, a lower IgG S/RBD (log10 BAU/mL) at 1 month post dose 3 was significantly associated with BTI, suggesting that a lower IgG level at this time point may predict BTI in this cohort of PWH.

Objectives. We comprehensively assessed health care utilization in a population-based sample of homeless adults and matched controls under a universal health insurance system. Methods. We assessed health care utilization by 1165 homeless single men and women and adults in families and their age- and gender-matched low-income controls in Toronto, Ontario, from 2005 to 2009, using repeated-measures general linear models to calculate risk ratios and 95% confidence intervals (CIs). Results. Homeless participants had mean rates of 9.1 ambulatory care encounters (maximum = 141.1), 2.0 emergency department (ED) encounters (maximum = 104.9), 0.2 medical–surgical hospitalizations (maximum = 14.9), and 0.1 psychiatric hospitalizations per person-year (maximum = 4.8). Rate ratios for homeless participants compared with matched controls were 1.76 (95% CI = 1.58, 1.96) for ambulatory care encounters, 8.48 (95% CI = 6.72, 10.70) for ED encounters, 4.22 (95% CI = 2.99, 5.94) for medical–surgical hospitalizations, and 9.27 (95% CI = 4.42, 19.43) for psychiatric hospitalizations. Conclusions. In a universal health insurance system, homeless people had substantially higher rates of ED and hospital use than general population controls; these rates were largely driven by a subset of homeless persons with extremely high-intensity usage of health services.

Background Research on discrimination in healthcare settings has primarily focused on health implications of race-based discrimination among ethno-racial minority groups. Little is known about discrimination experiences of other marginalized populations, particularly groups facing multiple disadvantages who may be subjected to other/multiple forms of discrimination. Objectives : (1) To examine the prevalence of perceived discrimination due to homelessness/poverty, mental illness/alcohol/drug related problems, and race/ethnicity/skin color while seeking healthcare in the past year among racially diverse homeless adults with mental illness; (2) To identify whether perceiving certain types of discrimination is associated with increased likelihood of perceiving other kinds of discrimination; and (3) To examine association of these perceived discrimination experiences with socio-demographic characteristics, self-reported measures of psychiatric symptomatology and substance use, and Emergency Department utilization. Methods We used baseline data from the Toronto site of the At Home/Chez Soi randomized controlled trial of Housing First for homeless adults with mental illness (n = 550). Bivariate statistics and multivariable logistic regression models were used for the analysis. Results Perceived discrimination related to homelessness/poverty (30.4%) and mental illness/alcohol/substance use (32.5%) is prevalent among ethnically diverse homeless adults with mental illness in healthcare settings. Only 15% of the total participants reported discrimination due to race/ethnicity/skin color. After controlling for relevant confounders and presence of psychosis, all types of discrimination in healthcare settings were associated with more frequent ED use, a greater - 3 - severity of lifetime substance abuse, and mental health problems. Perceiving discrimination of one type was associated with increased likelihood of perceiving other kinds of discrimination. Conclusions Understanding the experience of discrimination in healthcare settings and associated healthcare utilization is the first step towards designing policies and interventions to address health disparities among vulnerable populations. This study contributes to the knowledge base in this important area. Trial registration number This study has been registered with the International Standard Randomized Control Trial Number Register and assigned ISRCTN42520374 .