Effectiveness of Coronavirus Disease 2019 Vaccines Against Hospitalization and Death in Canada: A Multiprovincial, Test-Negative Design Study.

BACKGROUND: A major goal of coronavirus disease 2019 (COVID-19) vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of messenger RNA (mRNA) and ChAdOx1 COVID-19 vaccines against severe outcomes in 4 Canadian provinces between December 2020 and September 2021. METHODS: We conducted this multiprovincial, retrospective, test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random-effects models. RESULTS: We included 2 508 296 tested participants, with 31 776 COVID-19 hospitalizations and 5842 deaths. Vaccine effectiveness was 83% after a first dose and 98% after a second dose against both hospitalization and death (separately). Against severe outcomes, effectiveness was 87% (95% confidence interval [CI], 71%-94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95% CI, 96%-99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95% CI, 75%-94%) ≥56 days after a first dose, increasing to 97% (95% CI, 91%-99%) ≥56 days after a second dose. Lower 1-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules and against Alpha, Gamma, and Delta variants. CONCLUSIONS: Two doses of mRNA or ChAdOx1 vaccine provide excellent protection against severe outcomes.

What explains racial/ethnic inequities in the uptake of differentiated influenza vaccines?

We investigated the role of individual, community and vaccinator characteristics in mediating racial/ethnic disparities in the uptake of differentiated influenza vaccines (DIVs; including high-dose, adjuvanted, recombinant and cell-based vaccines). We included privately-insured (commercial and Medicare Advantage) ≥65 years-old community-dwelling health plan beneficiaries in the US with >1 year of continuous coverage and who received ≥1 influenza vaccine during the study period (July 2014-June 2018). Of 2.8 million distinct vaccination claims, 60% were for DIVs; lower if received in physician offices (49%) compared to pharmacies/facilities (74%). Among those vaccinated in physician offices, non-whites had lower odds of receiving a DIV if they lived in a non-minority county (0.77;95%CI 0.75-0.80) and even lower odds if they lived in a minority county (0.62;0.60-0.63). Differences in education, household income, medical history, community and vaccinator characteristics did not fully explain the disparities. Similar patterns emerged for vaccinations in pharmacies/facilities, although disparities disappeared altogether after controlling for socio-economic and vaccinator characteristics. When vaccinated in physician offices, minority county residents were less likely to receive a DIV, especially for non-whites (0.72;0.67-0.78). These disparities disappeared for whites, but not for non-whites, after controlling for community and vaccinator characteristics. We found an alarming level of inequity in DIV vaccine uptake among fully insured older adults that could not be fully explained by differences in sociodemographic, medical, community, and vaccinator characteristics. New strategies are urgently needed to address these inequities.

A Call for Caution in Use of Pertussis Vaccine Effectiveness Studies to Estimate Waning Immunity: A Canadian Immunization Research Network Study.

BACKGROUND: Vaccine effectiveness (VE) studies provide essential evidence on waning vaccine-derived immunity, a major threat to pertussis control. We evaluated how study design affects estimates by comparing 2 case-control studies conducted in Ontario, Canada. METHODS: We compared results from a test-negative design (TND) with a frequency-matched design (FMD) case-control study using pertussis cases from 2005-2015. In the first study, we identified test-negative controls from the public health laboratory that diagnosed cases and, in the second, randomly selected controls from patients attending the same physicians that reported cases, frequency matched on age and year. We compared characteristics of cases and controls using standardized differences. RESULTS: In both designs, VE estimates for the early years postimmunization were consistent with clinical trials (TND, 84%; FMD, 89% at 1-3 years postvaccination) but diverged as time since last vaccination increased (TND, 41%; FMD, 74% by 8 years postvaccination). Overall, we observed lower VE and faster waning in the TND than the FMD. In the TND but not FMD, controls differed from cases in important confounders, being younger, having more comorbidities, and higher healthcare use. Differences between the controls of each design were greater than differences between cases. TND controls were more likely to be unvaccinated or incompletely vaccinated than FMD controls (P < .001). CONCLUSIONS: The FMD adjusted better for healthcare-seeking behavior than the TND. Duration of protection from pertussis vaccines is unclear because estimates vary by study design. Caution should be exercised by experts, researchers, and decision makers when evaluating evidence on optimal timing of boosters.

Effectiveness of school-based and high-risk human papillomavirus vaccination programs against cervical dysplasia in Manitoba, Canada.

The effectiveness of a vaccination program is influenced by its design and implementation details and by the target population characteristics. Using routinely collected population-based individual-level data, we assessed the effectiveness (against cervical dysplasia) of Manitoba's quadrivalent human papillomavirus (qHPV) routine school-based vaccination program and a short-lived campaign that targeted women at high-risk of developing cervical cancer. Females ≥9 years old who received the qHPV vaccine in Manitoba (Canada) between September 1, 2006, and March 31, 2013 (N = 31,442) were matched on age and area of residence to up to three unvaccinated females. Cox proportional hazards models were used to estimate qHPV VE against high-grade (HSILs) and low-grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of undetermined significance (ASCUS). Among 14-17-year-old participants who had Pap cytology after enrollment, the adjusted qHPV VE estimates were 30% (17-58%) and 36% (21-48%) against the detection of HSILs and LSILs, respectively. There was, however, no evidence of program effectiveness among females vaccinated at ≥18 years of age and among those with a history of abnormal cytology, who were mostly vaccinated as part of the high-risk program. Estimates of VE for females vaccinated in the school-based program are consistent with the expected benefits from qHPV vaccination. No similar benefits were detected among women vaccinated at an older age, and those with abnormal cytology, who were targeted by the high-risk program. Further efforts should be targeted at achieving higher vaccine coverage among preadolescents, prior to the initiation of sexual activity.

Early Evidence of the Effectiveness of the Human Papillomavirus Vaccination Program Against Anogenital Warts in Manitoba, Canada: A Registry Cohort Study.

BACKGROUND: We assessed the effectiveness of the quadrivalent human papillomavirus vaccine (qHPV) vaccination program in Manitoba, Canada, in reducing incident anogenital warts (AGWs) and to what extent effectiveness depends on age at vaccination and number of doses. METHODS: Female participants 9 years or older who received the qHPV in Manitoba between September 2006 and March 2013 (n = 31,464) through the publicly funded school-based program and a high-risk catch-up program were included. They were matched on age and area of residence to unvaccinated female participants. Information on incident AGWs was obtained from provincial administrative databases using validated algorithms. Using stratified Cox regression models, we estimate hazard ratios (HRs) for the association between qHPV and AGWs. RESULTS: For female participants vaccinated at age 18 years or younger, receipt of qHPV was associated with a 40% reduction in AGW risk (HR, 0.6; 95% confidence interval [CI], 0.4-0.8). Further adjustment for socioeconomic and medical history did not alter this estimate. For women vaccinated at age 19 years or older, we saw an increase in AGW incidence, especially among those who were sexually active (HR, 2.8; 95% CI, 2.1-3.7). Among female participants vaccinated at age 18 years or younger, risk of AGWs was lowest among those who received 3 doses, corresponding to a vaccine effectiveness of 56% (95% CI, 30%-70%). For women vaccinated at older age, risk of AGWs remained increased regardless of the number of doses. CONCLUSIONS: Women vaccinated at an older (≥19 years) age may be less protected against AGWs, particularly if sexually active before vaccine administration. Further efforts should be targeted at increasing vaccine uptake among preadolescents before the initiation of sexual activity.

Distinct and shared three-dimensional chromosome organization patterns in lymphocytes, monoclonal gammopathy of undetermined significance and multiple myeloma.

The consistent appearance of specific chromosomal translocations in multiple myeloma has suggested that the positioning of chromosomes in the interphase nucleus might play a role in the occurrence of particular chromosomal rearrangements associated with malignant transformation. Using fluorescence in situ hybridization, we have determined the positions of selected chromosome pairs (18 and 19, 9 and 22, 4 and 14, 14 and 16, 11 and 14) in interphase nuclei of myeloma cells compared to normal lymphocytes of treatment-naïve patients. All chromosome pairs were arranged in a nonrandom pattern. Chromosomes commonly involved in myeloma-associated translocations (4 and 14, 14 and 16, 11 and 14) were found in close spatial proximity, and this is correlated with the occurrence of overlapping chromosome territories. The spatial distribution of chromosomes may increase the possibility of chromosomal translocations in multiple myeloma.

DNA Superresolution Structure of Reed-Sternberg Cells Differs Between Long-Lasting Remission Versus Relapsing Hodgkin's Lymphoma Patients.

Recent developments in microscopy have led to superresolution microscopy images of cells. Structured illumination microscopy was used before to reveal new details in the DNA structure and the structure of the DNA-free space in the DAPI-stained cell nuclei of the Hodgkin's lymphoma HDLM-2 cell line. This study extends this technology to primary pre-treatment classical Hodgkin's lymphoma samples of ten patients. Significant differences in both the DNA structure and the structure of the DNA-free space were detected between lymphocytes and malignant cells. Both types of structures were similar for lymphocytes of different patients. When the patients were un-blinded and grouped based on their clinical outcome, either non-relapsed or relapsed, a significant difference in the DNA structure of their Reed-Sternberg (RS) cells was found. Since, RS cells develop from mono-nucleated Hodgkin (H) cells, these data suggest distinct architectural restructuring of nuclei during RS cell formation in patients going to long-lasting remission versus relapse. J. Cell. Biochem. 117: 1633-1637, 2016. © 2015 Wiley Periodicals, Inc.

Quantitative superresolution microscopy reveals differences in nuclear DNA organization of multiple myeloma and monoclonal gammopathy of undetermined significance.

The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three-dimensional structured illumination microscopy (3D-SIM) increases the spatial resolution beyond the limits of conventional widefield fluorescence microscopy. 3D-SIM reveals new insights into the nuclear architecture of cancer as we show for the first time that it resolves organizational differences in intranuclear DNA organization of myeloma cells in MGUS and in MM patients. In addition, we report a significant increase in nuclear submicron DNA structure and structure of the DNA-free space in myeloma nuclei compared to normal lymphocyte nuclei. Our study provides previously unknown details of the nanoscopic DNA architecture of interphase nuclei of the normal lymphocytes, MGUS and MM cells. This study opens new avenues to understanding the disease progression from MGUS to MM.

Measuring murine chromosome orientation in interphase nuclei.

The nuclear architecture of a cell may change as a result of various diseases, including cancer. A variety of nuclear features are, therefore, of interest to cell biologists. Recently, several studies have investigated the orientation of chromosomes in the interphase nucleus either visually or semi-automatically. In this article an automated method to measure this orientation is presented. The theoretical difference between performing these measurements in two and three dimensions is discussed and experimentally verified. The results computed from measurements of murine nuclei correspond with results from visual inspection. We found significant differences in the orientation of chromosome 11 between nuclei from a PreB cell line of BALB/c origin and primary B nuclei from congenic [T38HxBALB/c]N wild-type mice. Since our new automatic method concurs with both the visual and semi-automatic methods, we conclude that the automatic method can replace these methods in assessing chromosome orientation.

Distinct nuclear orientation patterns for mouse chromosome 11 in normal B lymphocytes.

BACKGROUND: Characterizing the nuclear orientation of chromosomes in the three-dimensional (3D) nucleus by multicolor banding (mBANDing) is a new approach towards understanding nuclear organization of chromosome territories. An mBANDing paint is composed of multiple overlapping subchromosomal probes that represent different regions of a single chromosome. In this study, we used it for the analysis of chromosome orientation in 3D interphase nuclei. We determined whether the nuclear orientation of the two chromosome 11 homologs was random or preferential, and if it was conserved between diploid mouse Pre B lymphocytes of BALB/c origin and primary B lymphocytes of congenic [T38HxBALB/c]N wild-type mice. The chromosome orientation was assessed visually and through a semi-automated quantitative analysis of the radial and angular orientation patterns observed in both B cell types. RESULTS: Our data indicate that there are different preferential patterns of chromosome 11 orientation, which are not significantly different between both mouse cell types (p > 0.05). In the most common case for both cell types, both copies of chromosome 11 were oriented in parallel with the nuclear border. The second most common pattern in both types of B lymphocytes was with one homolog of chromosome 11 positioned with its telomeric end towards the nuclear center and with its centromeric end towards the periphery, while the other chromosome 11 was found parallel with the nuclear border. In addition to these two most common orientations present in approximately 50% of nuclei from each cell type, other orientations were observed at lower frequencies. CONCLUSIONS: We conclude that there are probabilistic, non-random orientation patterns for mouse chromosome 11 in the mouse B lymphocytes we investigated (p < 0.0001).

Differences in nuclear DNA organization between lymphocytes, Hodgkin and Reed-Sternberg cells revealed by structured illumination microscopy.

Advances in light microscopy have enabled the visualization of DNA in the interphase nucleus with more detail than is visible with conventional light microscopy. The nuclear architecture is assumed to be different in cancer cells compared to normal cells. In this paper we have studied, for the first time, the organization of nuclear DNA and that of DNA-free space in control lymphocytes, Hodgkin cells and Reed-Sternberg cells using 3D structured illumination microscopy (SIM). We have observed detail in these SIM images that was not observed in conventional widefield images. We have measured the size distribution of the DNA structure using granulometry and noted a significant, progressive increase in the amount of sub-micron structures from control lymphocytes to Hodgkin cells to Reed-Sternberg cells. The DNA-free space changes as well; "holes" in the DNA distribution start to appear in the malignant cells. We have studied whether these "holes" are nucleoli by staining for upstream binding factor (UBF), a protein associated with the nucleolus. We have found that the relative UBF content progressively and significantly decreases-or is absent-in the DNA-free space when measured as either the Pearson correlation coefficient with the DNA-free space or as the number of "holes" that contain UBF. Similar differences exist within the population of Reed-Sternberg cells between binucleated and multinucleated cells with four or more subnuclei. To our knowledge, this is the first study that investigates the changes of the nuclear DNA structure in any disease with superresolution light microscopy.

Three-dimensional structured illumination microscopy using Lukosz bound apodization reduces pixel negativity at no resolution cost.

The quality of the reconstructed image in structured illumination microscopy (SIM) depends on various aspects of the image filtering process. To optimize the trade-off between resolution and ringing artifacts, which lead to negative intensities, we extend Lukosz-bound filtering to 3D SIM and derive the parametrization of the 3D SIM cut-off. We compare the use of the Lukosz-bound as apodization filter to triangular apodization and find a tenfold reduction in the most negative pixel value with a minimal resolution loss. We test this algorithm on experimental SIM images of tubulin filaments and DAPI stained DNA structure in cancer cells and find a substantial reduction in the most negative pixel value and the percentage of pixels with a negative value. This means that there is no longer a need to clip the final image to avoid these negative pixel values.

Differential nuclear organization of translocation-prone genes in nonmalignant B cells from patients with t(14;16) as compared with t(4;14) or t(11;14) myeloma.

Gene organization in nonmalignant B cells from t(4;14) and t(11;14) multiple myeloma (MM) patients differs from that of healthy donors. Among recurrent IGH translocations in MM, the frequency of t(4;14) (IGH and FGFR3) or t(11;14) (IGH and CCND1) is greater than the frequency of t(14;16) (IGH and MAF). Gene organization in t(14;16) patients may influence translocation potential of MAF with IGH. In patients, three-dimensional FISH revealed the positions of IGH, CCND1, FGFR3, and MAF in nonmalignant B cells that are likely similar to those when MM first arose, compared with B cells from healthy donors. Overall, IGH occupies a more central nuclear position while MAF is more peripherally located. However, for B cells from t(4;14) and t(11;14) patients, IGH and FGFR3, or IGH and CCND1 are found in spatial proximity: IGH and MAF are not. This differs in B cells from t(14;16) patients and healthy donors where IGH is approximately equidistant to FGFR3, CCND1, and MAF, suggesting that gene organization in t(14;16) patients is different from that in t(4;14) or t(11;14) patients. Translocations between IGH and MAF may arise only in the absence of close proximity to the more frequent partners, as appears to be the case for individuals who develop t(14;16) MM.

Trends in Cemented Fixation in Hemiarthroplasty for Hip Fractures in Canada.

Bacground: The use of cemented fixation is widely recommended in hip arthroplasty for hip fractures, although it is not used universally. Methods: We describe the trends in cementing prevalence in hemiarthroplasty for hip fractures in Canada for patients ≥55 years old between April 2017 and March 2022. Results: The national prevalence of cemented fixation increased from 43% in 2017/18 to 58% in 2021/22, but there was a large variety of both the baseline prevalence and the trends across the country and between individual hospitals. The proportion of surgeons only performing cementless fixation fell from 30% to 21% between 2018/19 and 2021/22. Conclusions: As cemented fixation is now universally recommended, more coordination is needed to track these trends and to help drive implementation of this evidence-based practice across Canada.

Consistent Factors Influence Body Mass Index Thresholds for Total Joint Arthroplasty Across Health-Care Systems: A Qualitative Study.

BACKGROUND: Body mass index (BMI) thresholds are used as eligibility criteria to reduce complication risk in total joint arthroplasty (TJA). This approach oversimplifies preoperative risk assessment and inadvertently restricts access to effective surgical treatment for osteoarthritis. A prior survey of orthopaedic surgeons in the United States identified complex underlying factors that influence BMI considerations. To understand whether similar factors exist and influence surgeons in a different health-care system setting, we investigated Canadian surgeons' views and use of BMI criterion thresholds for TJA access. METHODS: A cross-sectional online qualitative survey was conducted with orthopaedic surgeons performing TJA in the Canadian health-care system. Responses were anonymous and questions were open-ended to allow for candid perspectives. Survey data were coded and a systematic process was followed to identify major themes. Findings were compared with U.S. surgeon perspectives. RESULTS: Sixty-nine respondents had a mean age of 49.0 ± 11.4 years (range, 33 to 79 years), with a mean surgical experience duration of 15.7 ± 11.4 years (range, 2 to 50 years). Surgeons reported variable use of BMI thresholds in practice. Twelve interconnected factors that influence BMI considerations were identified: (1) variable evidence interpretation, (2) surgical challenge, (3) surgeon beliefs and biases, (4) hospital differences, (5) access to resources, (6) health system bias, (7) patient health status, (8) patient body fat distribution, (9) patient decisional burden (to lose weight or accept risk), (10) evidence gaps and uncertainties, (11) need for innovation, and (12) societal views. Nine themes matched with findings from U.S. surgeons. CONCLUSIONS: Parallel to the United States, complex, interconnected factors influence Canadian orthopaedic surgeons' variable use of BMI restrictions for TJA eligibility. Despite different health-care systems and reimbursement models, similar technical and personal factors were identified. With TJA practice guidelines advising against hard BMI criteria, attention regarding access to resources, surgical training, and innovations to address TJA complexity in patients with large bodies are critically needed. Future advancements in this sphere must balance barrier removal with risk reduction to ensure safe and equitable surgical care. CLINICAL RELEVANCE: This study may influence surgeon behaviors with regard to hard BMI cutoffs for TJA and encourage critical thought about factors that influence decisions about surgical eligibility for patients with high BMI.

Randomized controlled trial comparing traditional versus enhanced-fixation designs of a novel cemented total knee arthroplasty tibial component.

Aims: A novel enhanced cement fixation (EF) tibial implant with deeper cement pockets and a more roughened bonding surface was released to market for an existing total knee arthroplasty (TKA) system.This randomized controlled trial assessed fixation of the both the EF (ATTUNE S+) and standard (Std; ATTUNE S) using radiostereometric analysis. Methods: Overall, 50 subjects were randomized (21 EF-TKA and 23 Std-TKA in the final analysis), and had follow-up visits at six weeks, and six, 12, and 24 months to assess migration of the tibial component. Low viscosity bone cement with tobramycin was used in a standardized fashion for all subjects. Patient-reported outcome measure data was captured at preoperative and all postoperative visits. Results: The patient cohort mean age was 66 years (SD seven years), 59% were female, and the mean BMI was 32 kg/m2 (SD 6 kg/m2). Mean two-year subsidence of the EF-TKA was 0.056 mm (95% confidence interval (CI) 0.025 to 0.086) versus 0.006 mm (95% CI -0.029 to 0.040) for the Std-TKA, and the two-year maximum total point motion (MTPM) was 0.285 mm (95% upper confidence limit (UCL) ≤ 0.363) versus 0.346 mm (95% UCL ≤ 0.432), respectively, for a mean difference of -0.061 mm (95% CI -0.196 to 0.074). Inducible displacement also did not differ between groups. The MTPMs between 12 and 24 months for each group was below the published threshold of 0.2 mm for predicting early aseptic loosening (p < 0.001 and p = 0.001, respectively). Conclusion: Both the enhanced fixation and the standard tibial implant design showed fixation with a predicted low risk of long-term aseptic loosening.

Socioeconomic, health-related, and primary care physician characteristics associated with adherence to seasonal influenza vaccination in Manitoba, Canada: A population-wide record-linkage cohort study.

OBJECTIVE: There is a lack of published evidence on factors associated with adherence (maintenance of cumulative vaccination) to seasonal influenza vaccination (SIV) in Manitoba, Canada. We sought to assess the associations. METHODS: A cohort study utilizing Manitoba administrative health databases. Participants received SIV in 2010/11 influenza season, remained registered Manitoba residents and received at least one SIV during the 2011/12‒2019/20 seasons. We dichotomized adherence into "more adherent" (6‒9 SIVs) and "less adherent" (1‒5 SIVs) and used multivariable adjusted generalized estimating equation logistic regression models to assess association between adherence and socioeconomic, health-related, and primary care physician (PCP) characteristics, stratified by age group (< 5, 5‒17, 18‒44, 45‒64, ≥ 65) and sex. Results are adjusted odds ratios with 95% confidence intervals. RESULTS: There were 152,493 participants. Males had lower odds of being more adherent except among ≥ 65-year-olds (1.03, 95% CI 1.01‒1.05). Compared with the lowest income quintile, those in higher income quintiles had higher odds of being more adherent. The odds mostly increased with increase in income quintile. Those with more contact with their PCP/hospitalization one year prior had higher odds of being more adherent. The odds increased with increased contact among those 18‒44, 45‒64 and ≥ 65 years old. Those who had PCP with more years of practice had higher odds of being more adherent. The odds increased as years of practice increased. These observations were mostly consistent irrespective of sex. CONCLUSION: Female gender, having higher income, having more contact with the health system, and having an experienced PCP may determine increased adherence to SIV in Manitoba. These findings require attention.

RéSUMé: OBJECTIF: Il y a un manque de données publiées sur les facteurs associés à l'adhésion vaccinale (le maintien de la vaccination cumulée) pour le vaccin contre la grippe saisonnière (VGS) au Manitoba (Canada). Nous avons cherché à évaluer ces associations. MéTHODE: Étude de cohorte utilisant les bases de données administratives sur la santé du Manitoba. Les participantes et les participants ont reçu le VGS durant la saison grippale 2010‒2011, ont continué d'être des résidents inscrits du Manitoba et ont reçu au moins un VGS au cours des saisons 2011‒2012 à 2019‒2020. Nous avons dichotomisé l'adhésion en « adhésion importante ¼ (6 à 9 VGS) et en « faible adhésion ¼ (1 à 5 VGS) et utilisé des modèles de régression logistique ajustés multivariés avec des équations d'estimation généralisées pour déterminer l'association entre l'adhésion et les caractéristiques liées au statut socioéconomique, à l'état de santé et au médecin de premier recours (MPR), stratifiées par groupe d'âge (< 5 ans, 5‒17 ans, 18‒44 ans, 45‒64 ans et ≥ 65 ans) et par sexe. Les résultats sont des rapports de cotes ajustés avec des intervalles de confiance de 95%. RéSULTATS: Il y a eu 152 493 personnes participantes. La probabilité d'une adhésion importante était inférieure chez les hommes, sauf chez les ≥ 65 ans (1,03, IC 95% 1,01‒1,05). La probabilité d'une adhésion importante était aussi plus élevée dans les quintiles de revenu supérieurs que dans le quintile de revenu inférieur. Cette probabilité augmentait principalement avec l'augmentation du quintile de revenu. Les personnes ayant eu plus de contacts avec leur MPR ou ayant été hospitalisées au cours de l'année antérieure étaient plus susceptibles d'afficher une adhésion importante. Cette probabilité augmentait avec l'augmentation des contacts dans les groupes d'âge de 18‒44 ans, de 45‒64 ans et de ≥ 65 ans. Les personnes dont le MPR exerçait depuis un grand nombre d'années étaient plus susceptibles d'afficher une adhésion importante. Cette probabilité augmentait avec le nombre d'années d'exercice. Ces observations étaient pour la plupart cohérentes quel que soit le sexe. CONCLUSION: Le sexe féminin, le revenu élevé, le fait d'avoir plus de contacts avec le système de santé et le fait d'avoir un MPR d'expérience peuvent déterminer l'adhésion accrue à la vaccination contre la grippe saisonnière au Manitoba. Ces constats méritent d'être pris en considération.

A population-based, province-wide, record-linkage interrupted time series analysis of impact of the universal seasonal influenza vaccination policy on seasonal influenza vaccine uptake among 5-64-year-olds in the province of Manitoba, Canada.

INTRODUCTION: Universal seasonal influenza vaccination policy (USIVP) was introduced in Manitoba, Canada in 2010. Its impact on seasonal influenza vaccine (SIV) uptake remains underexplored. METHODS: We used population-wide data from Manitoba to assess the impact of the USIVP on SIV uptake. The study covered twenty influenza seasons (2000/01-2019/20). We summarized SIV uptake for influenza seasons before and after the USIVP. Utilizing a single-group interrupted time series analysis and appropriately accounting for autocorrelation, we estimated absolute change and annual trend in SIV uptake percentages among 5-17-, 18-44-, and 45-64-year-olds across strata of certain population socioeconomic and health-related characteristics following the USIVP. RESULTS: Average SIV uptake percentage in all age groups was significantly higher after compared with before the USIVP. Following the USIVP, there was no significant absolute change in SIV uptake percentage among 18-44- and 45-64-year-olds overall; however, a significant decrease was observed among 18-44-year-old males in the higher income quintiles, across healthcare utilization, and in some regions of residence. A significant increase was observed among 5-17-year-olds in the lowest income quintiles, in Northern Manitoba, and among those with less healthcare utilization, and no chronic disease. Overall, there was mostly no significant annual trend in SIV uptake percentage among 18-44-year-olds, and while a significant upward and downward trend was observed among 5-17-year-olds and 45-64-year-olds, respectively, a significant downward trend was observed across all strata of population characteristics within all age groups in Northern Manitoba. CONCLUSIONS: The USIVP in Manitoba was followed by an absolute increase in SIV uptake percentage only in some socioeconomically disadvantaged subpopulations among 5-17-year-olds. While there was mostly an upward annual trend in SIV uptake percentage among 5-17-year-olds, a downward trend was observed among 45-64-year-olds and across all age groups and subpopulations in socioeconomically disadvantaged Northern Manitoba. These findings are novel for Manitoba and require investigation and public health attention.

Leveraging a clinical emergency department dataset to estimate two-dose COVID-19 vaccine effectiveness and duration of protection in Canada.

BACKGROUND: During the COVID-19 pandemic, clinical care shifted toward virtual and Emergency Department care. We explored the feasibility of mRNA vaccine effectiveness (VE) estimation against SARS-CoV-2-related Emergency Department visits and hospitalizations using prospectively collected Emergency Department data. METHODS: We estimated two-dose VE using a test-negative design and data from 10 participating sites of the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN). We included Emergency Department patients presenting with COVID-19 symptoms and nucleic acid amplification testing for SARS-CoV-2 between July 19 and December 31, 2021. We excluded patients with unclear vaccination and one or more than 2 vaccine doses by their Emergency Department visit. RESULTS: Among 3,405 eligible patients, adjusted two-dose mRNA VE against SARS-CoV-2-related Emergency Department visits was 93.3 % (95 % CI 87.9-96.3 %) between 7-55 days, sustained over 80 % through 139 days post-vaccination. In stratified analyses, VE was similar among patients with select immune-compromising conditions, chronic kidney disease, lung disease, unstable housing, and reported illicit substance use. CONCLUSIONS: Two-dose mRNA VE against SARS-CoV-2-related Emergency Department visit was high and sustained, including among vulnerable subgroups. Compared to administrative datasets, active Emergency Department enrolment enables standardization for testing access and indication and supports separate VE assessment among special population subgroups. Compared to other active enrolment settings, Emergency Departments more consistently function during crises when alternate healthcare sectors become variably closed. TRIAL REGISTRATION: Clinicaltrials.gov, NCT0470294.