Survival Benefit Associated With Participation in Clinical Trials of Anticancer Drugs: A Systematic Review and Meta-analysis.

Importance: Many cancer clinical investigators view clinical trials as offering better care for patients than routine clinical care. However, definitive evidence of clinical benefit from trial participation (hereafter referred to as the participation effect) has yet to emerge. Objective: To conduct a systematic review and meta-analysis of the evidence examining whether patient participation in cancer trials was associated with greater survival benefit compared with routine care. Data Sources: Studies were found through PubMed and Embase (January 1, 2000, until August 31, 2022), as well as backward and forward citation searching. Study Selection: Studies were included that compared overall survival of trial participants and routine care patients. Data Extraction and Synthesis: Data extraction and methodological quality assessment were completed by 2 independent coders using Covidence software. Data were pooled using a random-effects model and analyzed based on the quality of the comparison between trial participants and routine care patients (ie, extent to which studies controlled for bias and confounders). Main Outcomes and Measures: The hazard ratio (HR) for overall survival of trial participants vs routine care patients. Results: Thirty-nine publications were included, comprising 85 comparisons of trial participants and routine care patients. The meta-analysis revealed a statistically significant overall survival benefit for trial participants (HR, 0.76 [95% CI, 0.69-0.82]) when all studies were pooled, regardless of design or quality. However, survival benefits diminished in study subsets that matched trial participants and routine care patients for eligibility criteria (HR, 0.85 [95% CI, 0.75-0.97]) and disappeared when only high-quality studies were pooled (HR, 0.91 [95% CI, 0.80-1.05]). They also disappeared when estimates were adjusted for potential publication bias (HR, 0.94 [95% CI, 0.86-1.03]). Conclusions and Relevance: Many studies suggest a survival benefit for cancer trial participants. However, these benefits were not detected in studies using designs addressing important sources of bias and confounding. Pooled results of high-quality studies are not consistent with a beneficial effect of trial participation on its own.

Household Transmission Dynamics of Asymptomatic SARS-CoV-2-Infected Children: A Multinational, Controlled Case-Ascertained Prospective Study.

BACKGROUND: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. METHODS: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up. RESULTS: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC. CONCLUSIONS: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC.

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.

Characteristics and determinants of seasonal influenza vaccination in Manitoba, Canada: A population-wide record-linkage study.

Background: Seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba, Canada is consistently low notwithstanding vaccine availability and free-of-charge vaccination. Despite, there is a lack of published evidence on the determinants of uptake of the vaccine. We sought to assess the association between SIV uptake and certain population and primary care physician (PCP) characteristics in Manitoba. Methods: We conducted a longitudinal study utilizing Manitoba administrative health databases. We summarized SIV uptake from 2000/01-2019/20 influenza seasons across subpopulations defined by socioeconomic, health-related and PCP characteristics. Utilizing multivariable generalized estimating equation logistic regression models, we assessed the association between SIV uptake and the socioeconomic, health-related and PCP characteristics, stratified by age group (<5-, 5-17-, 18-44-, 45-64-, ≥65-year-olds) and sex. Results are adjusted odds ratios with associated 95 % confidence intervals. Results: SIV uptake percentage increased over time with 4.4 %, 13.1 %, 17.5 % and 21.7 % of < 5-year-olds, 2 %, 4.9 %, 9.7 % and 13.1 % of 5-17-year-olds, 5.4 %, 8.8 %, 10.7 % and 13.5 % of 18-44-year-olds, 16.8 %, 21.3 %, 23.6 % and 24.6 % of 45-64-year-olds receiving the SIV in 2000-2004, 2005-2009, 2010-2014 and 2015-2019, respectively. There was a decline among ≥ 65-year-olds from 58.5 % to 53.5 %. We observed a similar pattern across subpopulations. There were significantly increased odds of SIV uptake among females within the age groups ≥ 18 years, in higher income quintiles, mostly with increased contact with a PCP/hospitalization within age groups ≥ 18 years, among those who had older or female PCPs (the opposite observation among ≥ 65-year-olds) and whose PCP administered at least one SIV in prior influenza season. These observations were largely consistent irrespective of sex. Conclusion: SIV uptake in Manitoba appears to increase with age, and many socioeconomic, health-related and PCP characteristics appear to be associated with it. These findings may inform targeted vaccination programs to optimize influenza vaccination in Manitoba and similar Canadian jurisdictions.

Regional Disparities in the Uptake of Differentiated Influenza Vaccines in the United States.

Significant racial/ethnic inequities in the uptake of differentiated influenza vaccines (DIVs) have been previously reported, though less is known about regional disparities. We conducted a retrospective longitudinal study (2014/15-2017/18 influenza seasons) among privately insured adults aged 65 + years in the US. The exposure was the beneficiary's area of residence (US Census Bureau division) and the outcome was the type of influenza vaccine: differentiated (high-dose [HDV], adjuvanted, recombinant, and cell-based) versus conventional standard-dose egg-based. Multilevel logistic regression modeling, guided by a causal diagram, was used to assess the influence of socio-demographics, medical, healthcare utilization, community, and vaccinator characteristics in confounding or mediating regional disparities. Among those vaccinated in physician offices, beneficiaries in the East North Central region were twice as likely to receive a DIV vs those in the South Atlantic, whereas those in the East and West South Central were least likely. Disparities became more pronounced in models adjusted for individual and community characteristics, suggesting that crude uptake estimates understate the true magnitude of disparities. A vaccinator's previous HDV use was most influential in explaining regional differences. Similar but less pronounced patterns emerged for vaccinations in pharmacies/facilities. Regional disparities remained even in fully adjusted models, pointing to currently poorly understood factors that may include quality of healthcare, client health literacy and engagement, and other political and cultural factors.

Impact of the universal seasonal influenza vaccination policy in the province of Manitoba, Canada: A population-based, province-wide record-linkage study.

INTRODUCTION: In 2010, the government of the province of Manitoba, Canada introduced universal seasonal influenza vaccination policy (USIVP), providing free-of-charge vaccination to all registered residents of the province at least six months of age. Impact of the policy on seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba remains unclear, as there is a lack of published evaluations. METHODS: We conducted an ecological study, utilizing population-wide data from several linked de-identified Manitoba Health and Seniors Care administrative health databases. The study period was from 2000/01-2019/20 influenza seasons. The primary exposure was USIVP (five influenza seasons pre-policy [2005/06-2009/10] compared with post-policy [2010/11-2014/15]). The outcome was SIV uptake. We conducted pre/post logistic regression analysis stratified by age group (<5-, 5-17-, 18-44-, 45-64-, ≥65-year-olds) and certain population socioeconomic and health-related characteristics. Results are adjusted odds ratios with associated 95 % confidence intervals. RESULTS: We observed significantly increased adjusted odds of SIV uptake post-policy relative to pre-policy in all age groups except ≥65-year-olds already covered from inception of the vaccination programme. The adjusted odds ratios ranged from 0.76 (0.75-0.76) among ≥65-year-olds to 2.15 (2.13-2.18) among 5-17-year-olds, and were largely homogeneous within age groups across sex, income quintiles, regions of residence, and categories of number of visits to primary care physician/hospitalization one year prior to an influenza season except among <5- and 5-17-year-olds. These findings were mostly consistent irrespective of sex and region of residence although there was variability across income quintiles in Northern Manitoba region. CONCLUSIONS: Introduction of the USIVP in Manitoba was followed by a significant increase in SIV uptake in the five years post policy among <65-year-olds, with similar increased relative odds of vaccination observed within age groups across subpopulations. The observed variations in the relative odds of vaccination across income quintiles in Northern Manitoba region requires administrative attention.

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.

Patterns and predictors of referral to the specialized chronic lymphocytic leukemia clinic in Manitoba, Canada.

BACKGROUND: Better CLL patient survival has been reported for specialized CLL clinics/hematologists (compared to other CLL patients). It is possible that improved survival is driven by a better prognosis of referred patients. METHODS: We used logistic regression to calculate the odds ratios (ORs) and 95 % confidence intervals 95 %CIs) of the association between patient characteristics and CLL referral of all persons diagnosed in 2005-2016 with a pathologically-confirmed CLL or SLL. RESULTS: Two-thirds of 1293 patients were referred to the CLL clinic. Referred patients were younger (16 % vs 44 % were 80 +) and in better health (47 % vs 56 % with a chronic diseases) than non-referred patients. Referral increased over time: in 2005-2010, about 60 % of patients were referred; in 2011-2016, this increased to 76 %. Gender did not affect referral (the OR for females is 1.0, 95 %CI 0.8-1.2), but age played a major role; CLL patients diagnosed at age 80 + were less likely to be referred than patients diagnosed < 60, 0.2 (0.1-0.3). CONCLUSION: Because referral to Manitoba's specialized CLL clinic is associated with age and the patient's overall health before referral, one should be careful in interpreting differences in outcomes between CLL patients based on referral status alone.

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.

Methods to account for measured and unmeasured confounders in influenza relative vaccine effectiveness studies: A brief review of the literature.

Observational seasonal influenza relative vaccine effectiveness (rVE) studies employ a variety of statistical methods to account for confounding and biases. To better understand the range of methods employed and implications for policy, we conducted a brief literature review. Across 37 included rVE studies, 10 different types of statistical methods were identified, and only eight studies reported methods to detect residual confounding, highlighting the heterogeneous state of the literature. To improve the comparability and credibility of future rVE research, researchers should clearly explain methods and design choices and implement methods to detect and quantify residual confounding.

Incidence of anogenital warts after the introduction of the quadrivalent HPV vaccine program in Manitoba, Canada.

BACKGROUND: The incidence of anogenital warts (AGW) decreased after the introduction of the quadrivalent human papillomavirus (qHPV) vaccine in multiple jurisdictions. We studied how comparing AGW incidence rates with different outcomes affects the interpretation of the qHPV vaccination program. To do this, we replicated multiple study designs within a single jurisdiction (Manitoba). METHODS: We measured the incidence rates of AGW, AGW-related prescriptions, chlamydia, and gonorrhea (the latter two as sham outcomes) between 2001 and 2017 using several clinical and administrative health databases from Manitoba. We then used incidence rate ratios (IRRs) to compare, for each outcome, the rate for the 1997-1998 birth cohort (the first cohorts eligible for the publicly funded qHPV vaccination program) and the older 1995-1996 birth cohort. RESULTS: AGW incidence in Manitoba dropped 72% (95% confidence interval 54-83%) among 16-18 year-old girls and 51% (14-72%) among boys after the introduction of the female-only qHPV vaccination program. Trends in AGW-related prescriptions were different from trends in AGW diagnoses as these prescriptions peaked shortly after the introduction of the publicly funded qHPV vaccine program. Chlamydia and gonorrhea incidence rates also decreased 12% (5-18%) and 16% (-1-30%), respectively, for 16-18 year-old girls. CONCLUSIONS: The publicly funded school-based qHPV vaccine program reduced AGW incidence in Manitoba by three-quarters in young females. AGW-related prescriptions are a poor proxy for medically attended AGW after the introduction of the publicly funded qHPV vaccination program. Different sexual habits in adolescents are, at most, responsible for a small portion of the reduction in AGW incidence.

Influenza vaccine in chronic obstructive pulmonary disease among elderly male veterans.

BACKGROUND: Prior studies have established those elderly patients with chronic obstructive pulmonary disease (COPD) are at elevated risk for developing influenza-associated complications such as hospitalization, intensive-care admission, and death. This study sought to determine whether influenza vaccination could improve survival among elderly patients with COPD. MATERIALS/METHODS: This study included Veterans (age ≥ 65 years) diagnosed with COPD that received care at the United States Veterans Health Administration (VHA) during four influenza seasons, from 2012-2013 to 2015-2016. We linked VHA electronic medical records and Medicare administrative files to Centers for Disease Control and Prevention National Death Index cause of death records as well as influenza surveillance data. A multivariable time-dependent Cox proportional hazards model was used to compare rates of mortality of recipients of influenza vaccination to those who did not have records of influenza vaccination. We estimated hazard ratios (HRs) adjusted for age, gender, race, socioeconomic status, comorbidities, and healthcare utilization. RESULTS: Over a span of four influenza seasons, we included 1,856,970 person-seasons of observation where 1,199,275 (65%) had a record of influenza vaccination and 657,695 (35%) did not have a record of influenza vaccination. After adjusting for comorbidities, demographic and socioeconomic characteristics, influenza vaccination was associated with reduced risk of death during the most severe periods of influenza seasons: 75% all-cause (HR = 0.25; 95% CI: 0.24-0.26), 76% respiratory causes (HR = 0.24; 95% CI: 0.21-0.26), and 82% pneumonia/influenza cause (HR = 0.18; 95% CI: 0.13-0.26). A significant part of the effect could be attributed to "healthy vaccinee" bias as reduced risk of mortality was also found during the periods when there was no influenza activity and before patients received vaccination: 30% all-cause (HR = 0.70; 95% CI: 0.65-0.75), 32% respiratory causes (HR = 0.68; 95% CI: 0.60-0.78), and 51% pneumonia/influenza cause (HR = 0.49; 95% CI: 0.31-0.78). However, as a falsification study, we found that influenza vaccination had no impact on hospitalization due to urinary tract infection (HR = 0.97; 95% CI: 0.80-1.18). CONCLUSIONS: Among elderly patients with COPD, influenza vaccination was associated with reduced risk for all-cause and cause-specific mortality.

The impact of pertussis vaccine programme changes on pertussis disease burden in Manitoba, 1992-2017-an age-period-cohort analysis.

BACKGROUND: Changes to pertussis vaccination programmes can have impacts on disease burden that should be estimated independently from factors such as age- and period-related trends. We used age-period-cohort (APC) models to explore pertussis incidence in Manitoba over a 25-year period (1992-2017). METHODS: We identified all laboratory-confirmed cases of pertussis from Manitoba's Communicable Diseases Database and calculated age-standardized incidence rates. We used APC models to investigate trends in pertussis incidence. RESULTS: During the study period, 2479 cases were reported. Age-standardized rates were highest during a large outbreak in 1994 (55 cases/100 000 person-years), with much lower peaks in 1998, 2012 and 2016. We saw strong age and cohort effects in the APC models, with a steady decrease in incidence with increasing age and increased risk in the cohort born between 1980 and 1995. CONCLUSIONS: The highest risk for pertussis was consistently in young children, regardless of birth cohort or time period. The 1981 programme change to an adsorbed whole-cell pertussis vaccine with low effectiveness resulted in reduced protection in the 1981-95 birth cohort and contributed to the largest outbreak of disease during the 25-year study period.

Exploring the reasons for low pertussis vaccine effectiveness in Ontario, Canada, 2006-2008: a Canadian Immunization Research Network study.

OBJECTIVES: Although pertussis vaccines have been widely used for many decades, a burden of illness persists. Resurgences in Ontario, Canada, have not been substantial in the past decade, but an outbreak of pertussis occurred in Toronto between 1 October 2005 and 31 March 2006. Previous Ontario studies found high vaccine effectiveness (VE) in the initial years post-immunization. In order to explore the impact of outbreaks and external factors on VE, we investigated pertussis VE during the period 2006-2008. METHODS: We assessed pertussis VE using a frequency-matched case-control study for the period 1 March 2006 to 31 December 2008. We used logistic regression to estimate VE by age, time since last vaccination, and vaccination status according to the Ontario recommended schedule. We compared analyses including and excluding cases from Toronto, and to two recent Ontario pertussis VE studies. RESULTS: We included 1797 confirmed cases and 7188 matched controls. Most cases were under 4 years of age during the study period. Pertussis VE was 3.8% (95% CI: - 21.0, 24.0) in the period 15-364 days following the last pertussis vaccine dose, and increased with increasing time since vaccination. Pertussis VE in the first 15-364 days excluding Toronto increased to 57.1% (95% CI: 26.0, 75.1), but the trend of increasing VE with time since vaccination persisted. Although VE was higher in older (6-11 years) than younger (0-5 years) children, it was lower at 12-13 years than after 14 years. CONCLUSION: VE was lower in comparison with other studies conducted in Ontario, particularly in younger children. Various factors occurring during the study period may have influenced the results, including clinical testing of asymptomatic contacts, laboratory testing and methods and reporting practice, and a sensitive case definition. Further studies are needed to optimize methods for measuring VE to inform pertussis vaccine policy.

RéSUMé: OBJECTIFS: Bien que les vaccins anticoquelucheux soient couramment utilisés depuis des dizaines d'années, la charge de morbidité de la coqueluche persiste. Sa réapparition en Ontario, au Canada, a été modérée au cours des 10 dernières années, mais une éclosion de coqueluche s'est produite à Toronto entre le 1er octobre 2005 et le 31 mars 2006. Des études antérieures menées en Ontario ont fait état d'une efficacité vaccinale (EV) élevée dans les premières années qui suivent l'immunisation. Pour explorer l'impact des éclosions et des facteurs externes sur l'EV, nous avons étudié l'efficacité des vaccins anticoquelucheux pour la période 2006-2008. MéTHODE: Nous avons évalué l'efficacité des vaccins anticoquelucheux à l'aide d'une étude cas-témoins assortie par fréquence pour la période du 1er mars 2006 au 31 décembre 2008. Nous avons procédé par régression logistique pour estimer l'EV selon l'âge, le temps écoulé depuis la dernière vaccination et le statut vaccinal d'après le calendrier recommandé en Ontario. Nous avons comparé les analyses en incluant et en excluant les cas de Toronto et par rapport à deux récentes études ontariennes sur l'efficacité des vaccins anticoquelucheux. RéSULTATS: Nous avons inclus 1 797 cas confirmés et 7 188 témoins assortis. La plupart des cas avaient moins de 4 ans durant la période de l'étude. L'efficacité des vaccins anticoquelucheux était de 3,8 % (IC de 95 % : -21,0, 24,0) au cours des 15 à 364 jours suivant la dernière dose de vaccin anticoquelucheux et augmentait avec le temps après la vaccination. En excluant Toronto, l'efficacité des vaccins anticoquelucheux au cours des 15 à 364 premiers jours passait à 57,1 % (IC de 95 % : 26,0, 75,1), mais la tendance d'augmentation de l'EV avec le temps après la vaccination était toujours présente. Bien que l'EV ait été supérieure chez les enfants plus vieux (6 à 11 ans) que chez les plus jeunes (0 à 5 ans), elle était plus faible chez les 12-13 ans qu'après 14 ans. CONCLUSION: Nous avons observé une EV plus faible que dans d'autres études menées en Ontario, surtout chez les jeunes enfants. Divers facteurs survenus durant la période de l'étude pourraient en avoir influencé les résultats, dont les tests cliniques menés sur les contacts asymptomatiques, les épreuves et les méthodes de laboratoire, les pratiques de déclaration et l'usage d'une définition de cas sensible. D'autres études sont nécessaires pour optimiser la méthode de mesure de l'EV afin d'éclairer la politique vaccinale contre la coqueluche.

Economic Assessment of High-Dose Versus Adjuvanted Influenza Vaccine: An Evaluation of Hospitalization Costs Based on a Cohort Study.

Two influenza vaccines are licensed in the U.S. exclusively for the 65 years and older population: a trivalent inactivated high-dose influenza vaccine (HD-IIV3) and a trivalent inactivated adjuvanted influenza vaccine (aIIV3). In a recent publication, we estimated a relative vaccine effectiveness (rVE) of HD-IIV3 vs. aIIV3 of 12% (95% CI: 3.3-20%) for influenza-related hospitalizations using a retrospective study design, but did not report the number of prevented hospitalizations nor the associated avoided cost. In this paper we report estimations for both. METHODS: Leveraging the rVE of a cohort study over two influenza seasons (2016/17 and 2017/18), we collected cost data for healthcare provided to the same study population. Vaccine costs were obtained from the Medicare pricing schedule. Our economic assessment compared cost of vaccination and hospital care for patients experiencing acute respiratory or cardiovascular illness. RESULTS: We analyzed 1.9 million HD-IIV3 and 223,793 aIIV3 recipients. Average vaccine list prices were $46.23 for HD-IIV3 and $48.26 for aIIV3. The hospitalization rates for respiratory disease in HD-IIV3 and aIIV3 recipients were 187 (95% CI: 185-189) and 212 (195-231) per 10,000 persons-years, respectively. Attributing the average cost per hospitalization of $12,652 ($12,214-$13,090) to the difference in hospitalization rates, we estimate net savings of HD-IIV3 to be $34 ($10-$62) per recipient. CONCLUSION: Pooled over two predominantly A/H3N2 respiratory seasons, vaccination with HD-IIV3 was associated with lower hospitalization rates and associated costs compared to aIIV3 in senior members of a large national managed health care company in the U.S. Reduced hospitalizations affect healthcare utilization overall, and therefore other costly health outcomes.

Patterns and descriptors of COVID-19 testing and lab-confirmed COVID-19 incidence in Manitoba, Canada, March 2020-May 2021: A population-based study.

BACKGROUND: We studied lab-confirmed COVID-19 infection (LCCI) testing, incidence, and severity. METHODS: We included all Manitoba residents and limited our severity analysis to LCCI patients. We calculated testing, incidence and vaccination rates between March 8, 2020 and June 1, 2021. We estimated the association between patient characteristics and testing (rate ratio [RR]; Poisson regression), including the reason for testing (screening, symptomatic, contact/outbreak asymptomatic), incidence (hazard ratio [HR]; Cox regression), and severity (prevalence ratio [PR], Cox regression). FINDINGS: The overall testing rate during the second/third wave was 570/1,000 person-years, with an LCCI rate of 50/1,000 person-years. The secondary attack rate during the second/third wave was 16%. Across regions, young children (<10) had the lowest positivity for symptomatic testing, the highest positivity for asymptomatic testing, and the highest risk of LCCI as asymptomatic contact. People in the lowest income quintile had the highest risk of LCCI, 1.3-6x the hazard of those in the highest income quintile. Long-term care (LTC) residents were particularly affected in the second wave with HRs>10 for asymptomatic residents. INTERPRETATION: Although the severity of LCCI in children was low, they have a high risk of asymptomatic positivity. The groups most vulnerable to LCCI, who should remain a focus of public health, were residents of Manitoba's North, LTC facilities, and low-income neighbourhoods. FUNDING: Canada Research Chair Program.

Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study.

OBJECTIVE: To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death). DESIGN: Test negative design study. SETTING: Ontario, Canada between 14 December 2020 and 19 April 2021. PARTICIPANTS: 324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2. INTERVENTIONS: BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. MAIN OUTCOME MEASURES: Laboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes. RESULTS: Of 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation. CONCLUSIONS: Two doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.

Pertussis vaccine effectiveness and duration of protection - A systematic review and meta-analysis.

A comprehensive review of observational pertussis vaccine effectiveness (VE) studies is needed to update gaps from previous reviews. We conducted a systematic review of VE and duration of protection studies for the whole-cell (wP) and acellular (aP) pertussis vaccines and conducted a formal meta-analysis using random effects models. Evidence continues to suggest that receipt of any pertussis vaccine confers protection in the short-term against disease although this protection wanes rapidly for aP vaccine. We detected significant heterogeneity in pooled estimates due, in part, to factors such as bias and confounding which may be mitigated by study design. Our review of possible sources of heterogeneity may help interpretation of other VE studies and aid design decisions in future pertussis VE research.

A multisite study of pertussis vaccine effectiveness by time since last vaccine dose from three Canadian provinces: A Canadian Immunization Research Network study.

BACKGROUND: Pertussis remains poorly controlled relative to other diseases targeted by childhood vaccination programs. We combined estimates from four population-based studies of pertussis vaccine effectiveness (VE) in three Canadian provinces using a meta-analytic approach to improve precision and explore regional variation in VE and durability of protection. METHODS: Studies were conducted in Alberta, Manitoba, and Ontario over periods ranging from 1996 to 2015. Adjusted log odds ratios (OR; VE = 100*[1-OR]) of the effect of vaccination on pertussis risk were estimated by time since last vaccination in each study and pooled using DerSimonian and Laird random-effects models. We used the I2 statistic to estimate between-study heterogeneity and assessed methodological and clinical heterogeneity through subgroup analyses of study design and age. RESULTS: Data on 3,270 pertussis cases and 23,863 controls were available. Pertussis VE declined from 86% (95% CI 79%-90%, I2 = 81.5%) at < 1 year since last vaccination to 51% (11%-74%, I2 = 80.9%) by ≥ 8 years. Effect estimates were the most heterogeneous in the least and most elapsed time periods since last vaccine dose. This was attributable mostly to variation between provinces in the distribution of age groups and number of vaccine doses received within time periods, as well as study design and small numbers in the most elapsed time period. INTERPRETATION: Consistent trends of decreasing pertussis VE with increasing time since last vaccination across three Canadian provinces indicate the need for immunization schedules and vaccine development to optimize protection for all individuals, especially for adolescents and young adults at greatest risk of infection.