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Background: The expansion of pharmacist scope of practice to include provision of immunizations has occurred or is being considered in various countries. There are limited data evaluating the experiences of Canadian pharmacists in their role as immunizers. Objective: To describe the experiences of pharmacists in the Canadian province of New Brunswick as immunizers, including vaccines administered and perceived barriers and facilitators to providing immunizations. Methods: An anonymous, self-administered, web-based questionnaire was offered via email by the New Brunswick Pharmacists’ Association to all its members. The survey tool was adapted, with permission, from a tool previously used by the American Pharmacists Association and validated using content validity and test-retest reproducibility. Pharmacist reported immunization activities and perceived facilitators and barriers to providing immunization services were assessed. Results: Responses from 168 (response rate of 26%) were evaluable. Approximately 90% of respondents worked in community practice full time, 65% were female and 44% were practicing for 20 or more years. Greater than 75% reported administering: hepatitis A and B, influenza, and zoster vaccines. The majority of respondents felt fully accepted (agreed or strongly agreed) as immunization providers by patients, local physicians, and the provincial health department (97%, 70%, and 78%, respectively). Most commonly reported barriers were: lack of a universally funded influenza immunization program, insufficient staffing and space, and concerns around reimbursement for services. Conclusions: Pharmacists in New Brunswick, Canada are actively participating in the provision of a variety of immunizations and felt fully supported by patients and other healthcare providers. Barriers identified may provide insight to other jurisdictions considering expanding the role of pharmacists as immunizers.

Since the 1990s, reports of Q fever in Nova Scotia, Canada, have declined. Passive surveillance for Q fever in Nova Scotia and its neighboring provinces in eastern Canada indicates that the clinical manifestation of Q fever in the Maritime provinces is pneumonia and that incidence of the disease may fluctuate. [ABSTRACT FROM AUTHOR]

This qualitative, cross-sectional study aimed to understand the barriers and facilitators related to the adherence and completion of the recombinant zoster vaccine (RZV) two-dose series in Canada, as perceived by healthcare providers (HCPs) and patients. Data collection occurred via 60-minute concept elicitation interviews with 12 HCPs (4 physicians, 2 nurse practitioners, 6 pharmacists) who had prescribed and/or administered RZV in Canada, and 21 patients aged ≥50 years who had received ≥1 dose of RZV. Patients were categorized as adherent (received both doses within the recommended 2-to-6-month timeframe; n  = 11) or non-adherent (received only one dose or second dose outside the recommended timeframe; n  = 10). Interview transcripts were coded and analyzed using a two-part thematic analysis approach. HCP-identified barriers to RZV adherence included high out-of-pocket cost, inconsistent/lack of health plan coverage, inconvenient processes for accessing RZV, and patient forgetfulness. HCP-identified facilitators included desire for shingles protection, HCP encouragement, and reminders. Barriers to RZV adherence identified by patients included lack of HCP knowledge/experience with RZV, receiving unreliable/confusing information, having unpleasant/severe side effects following the first dose, high out-of-pocket cost, lack of insurance coverage, and forgetfulness. Patient-identified facilitators included self-motivation, financial support, convenient processes for obtaining RZV, and reminders. In conclusion, many factors can influence RZV series completion and adherence among adults in Canada, including cost, insurance coverage, HCP knowledge and encouragement, and reminders. Awareness of these factors may inform HCPs in helping patients overcome barriers and identify opportunities for future consideration, facilitating protection against herpes zoster.

Background: The demand for COVID-19 vaccines has diminished as the pandemic lingers. Understanding vaccine hesitancy among essential workers is important in reducing the impact of future pandemics by providing effective immunization programs delivered expeditiously., Method: Two surveys exploring COVID-19 vaccine acceptance in 2021 and 2022 were conducted in cohorts of health care providers (HCP) and education workers participating in prospective studies of COVID-19 illnesses and vaccine uptake. Demographic factors and opinions about vaccines (monovalent and bivalent) and public health measures were collected in these self-reported surveys. Modified multivariable Poisson regression was used to determine factors associated with hesitancy., Results: In 2021, 3 % of 2061 HCP and 6 % of 3417 education workers reported hesitancy (p < 0.001). In December 2022, 21 % of 868 HCP and 24 % of 1457 education workers reported being hesitant to receive a bivalent vaccine (p = 0.09). Hesitance to be vaccinated with the monovalent vaccines was associated with earlier date of survey completion, later receipt of first COVID-19 vaccine dose, no influenza vaccination, and less worry about becoming ill with COVID-19. Factors associated with hesitance to be vaccinated with a bivalent vaccine that were common to both cohorts were receipt of two or fewer previous COVID-19 doses and lower certainty that the vaccines were safe and effective., Conclusion: Education workers were somewhat more likely than HCP to report being hesitant to receive COVID-19 vaccines but reasons for hesitancy were similar. Hesitancy was associated with non-receipt of previous vaccines (i.e., previous behaviour), less concern about being infected with SARS-CoV-2, and concerns about the safety and effectiveness of vaccines for both cohorts. Maintaining inter-pandemic trust in vaccines, ensuring rapid data generation during pandemics regarding vaccine safety and effectiveness, and effective and transparent communication about these data are all needed to support pandemic vaccination programs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brenda L Coleman reports financial support was provided by Canadian Institutes of Health Research. Allison McGeer reports financial support was provided by Canadian Institutes of Health Research. Allison McGeer reports financial support was provided by Physicians' Services Inc. Foundation. Dawn Bowdish reports financial support was provided by Weston Family Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We developed and validated the Influenza Severity Scale (ISS), a standardized risk assessment for influenza, to estimate and predict the probability of major clinical events in patients with laboratory-confirmed infection. Data from the Canadian Immunization Research Network's Serious Outcomes Surveillance Network (2011/2012-2018/2019 influenza seasons) enabled the selecting of all laboratory-confirmed influenza patients. A machine learning-based approach then identified variables, generated weighted scores, and evaluated model performance. This study included 12,954 patients with laboratory-confirmed influenza infections. The optimal scale encompassed ten variables: demographic (age and sex), health history (smoking status, chronic pulmonary disease, diabetes mellitus, and influenza vaccination status), clinical presentation (cough, sputum production, and shortness of breath), and function (need for regular support for activities of daily living). As a continuous variable, the scale had an AU-ROC of 0.73 (95% CI, 0.71-0.74). Aggregated scores classified participants into three risk categories: low (ISS < 30; 79.9% sensitivity, 51% specificity), moderate (ISS ≥ 30 but < 50; 54.5% sensitivity, 55.9% specificity), and high (ISS ≥ 50; 51.4% sensitivity, 80.5% specificity). ISS demonstrated a solid ability to identify patients with hospitalized laboratory-confirmed influenza at increased risk for Major Clinical Events, potentially impacting clinical practice and research., (© 2024. The Author(s).)

Background: The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like-illnesses from >100 participating clinical sites worldwide based on a core protocol and consistent case definitions., Methods: We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income level., Results: The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2., Conclusions: Our study provides new information on influenza severity in underresourced populations, particularly those in LMICs., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Influenza and RSV coinfections are not commonly seen but are concerning as they can lead to serious illness and adverse clinical outcomes among vulnerable populations. Here we describe the clinical features and outcomes of influenza and RSV coinfections in hospitalized adults., Methods: A cohort study was performed with pooled active surveillance in hospitalized adults ≥ 50 years from the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) during the 2012/13, 2013/14, and 2014/15 influenza seasons. Descriptive statistics summarized the characteristics of influenza/RSV coinfections. Kaplan-Meier estimated the probability of survival over the first 30 days of hospitalization., Results: Over three influenza seasons, we identified 33 cases of RSV and influenza coinfection, accounting for 2.39 cases per 1,000 hospitalizations of patients with acute respiratory illnesses. Adults aged 50 + years commonly reported cough (81.8%), shortness of breath (66.7%), sputum production (45.5%), weakness (33.3%), fever (27.3%), and nasal congestion (24.2%) as constitutional and lower respiratory tract infection symptoms. The mortality rate was substantial (12.1%), and age, comorbidity burden, and frailty were associated with a higher risk for adverse clinical outcomes., Conclusions: Older adults are at higher risk for complications from influenza and RSV coinfections, especially those over 65 with a high comorbidity burden and frailty., (© 2024. The Author(s).)

Importance: In hospitals during the COVID-19 pandemic, laboratory testing was important to reduce SARS-CoV-2 transmissions, while facilitating patient flow in the emergency department and pre-operative settings, and allowing for the safe return to work of exposed healthcare workers. Delayed test results from laboratory nucleic acid amplification tests (NAATs) posed a barrier to maximizing efficient patient flow and minimizing staffing shortages. This quality improvement project sought to evaluate the analytical and clinical performance of the Lucira Check-It COVID-19 Test, a point-of-care test that used NAAT technology, in the perioperative setting, emergency department, and community testing sites. We found the Lucira Check-It to have comparable performance to laboratory NAATs. It can be employed with little training for specimen collection, processing, and interpretation, and at a cost justifiable from the resources saved from avoiding sample transport and laboratory testing., Competing Interests: The authors declare no conflict of interest.

Background: Influenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults., Methods: A test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI)., Results: Of 7,101 adults aged ≥ 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%-51.1%) for naTIV and 53.5% (42.8%-62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%-66.8%) for aTIV and 44.8% (39.1%-50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61-0.92), demonstrating statistically significant benefit favoring aTIV., Conclusions: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HP reports grant funding from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. MKA reports grant funding from the GSK group of companies, Pfizer and Sanofi Pasteur and honoraria from Sanofi, Seqirus and Pfizer for past ad hoc advisory activities. TFH reports grants from Pfizer and GSK, outside the submitted work. AMcG reports payments to her institution from the GSK group of companies for the conduct of this study, and payments from GSK, Seqirus and Sanofi Pasteur, outside the submitted work. ML reports payments from Sanofi, Medicago, Sequirus, and Pfizer outside the submitted work. AP reports payments from Actelion, Sanofi-Pasteur, and Genentech outside the submitted work. JP reports payments from the GSK group of companies, Merck, Roche, and Synthetic Biologics, outside the submitted work. MS reports payments from the GSK group of companies and Pfizer during the study. SAM reports grants and payments from Pfizer, GSK, Merck, Novartis and Sanofi, outside the submitted work. outside the submitted work. ZS, MKN, JJL, ME, GB, WB, PL-W, LV, GT, LY, AA, JJ, KK, DR, DW, DS, GS, ST, SS, AMcC and KK report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Respiratory syncytial virus (RSV) disease in older adults is undercharacterized. To help inform future immunization policies, this study aimed to describe the disease burden in Canadian adults aged ≥50 years hospitalized with RSV., Methods: Using administrative data and nasopharyngeal swabs collected from active surveillance among adults aged ≥50 years hospitalized with an acute respiratory illness (ARI) during the 2012-2013, 2013-2014, and 2014-2015 influenza seasons, RSV was identified using a respiratory virus multiplex polymerase chain reaction test to describe the associated disease burden, incidence, and healthcare costs., Results: Of 7797 patients tested, 371 (4.8%) were RSV positive (2.2% RSV-A and 2.6% RSV-B). RSV prevalence varied by season from 4.2% to 6.2%. Respiratory virus coinfection was observed in 11.6% (43/371) of RSV cases, with influenza A being the most common. RSV hospitalization rates varied between seasons and increased with age, from 8-12 per 100 000 population in adults aged 50-59 years to 174-487 per 100 000 in adults aged ≥80 years. The median age of RSV cases was 74.9 years, 63.7% were female, and 98.1% of cases had ≥1 comorbidity. Among RSV cases, the mean length of hospital stay was 10.6 days, 13.7% were admitted to the intensive care unit, 6.4% required mechanical ventilation, and 6.1% died. The mean cost per RSV case was $13 602 (Canadian dollars) but varied by age and Canadian province., Conclusions: This study adds to the growing literature on adult RSV burden by showing considerable morbidity, mortality, and healthcare costs in hospitalized adults aged ≥50 years with ARIs such as influenza., Competing Interests: Potential conflicts of interest. M. K. A. reports grant funding from the GSK group of companies, Pfizer, and Sanofi Pasteur, outside the submitted work, and past payments for ad hoc advisory activities from Seqirus, Pfizer, and Sanofi. T. F. H. reports grant funding from the GSK group of companies, and payments from Pfizer and AbbVie, outside the submitted work. S. A. H. reports payments from the GSK group of companies, during the conduct of the study and outside the submitted work. J. M. L. reports payments from the GSK group of companies and CIHR, during the conduct of the study, and reports payment from the GSK group of companies, outside the submitted work. J. J. L. reports payments from Pfizer, Merck, Janssen, and Sanofi, outside the submitted work. J. E. M. reports payments to her institution from GlaxoSmithKline group of companies, and Sanofi Pasteur, outside the submitted work. J. P. reports payments from the GSK group of companies, Merck, Roche, and Synthetic Biologics, outside the submitted work. M. S. reports payments from the GSK group of companies and Pfizer, during the conduct of the study. S. T. reports payments from CIHR, during the conduct of the study. L. V. reports payments from the GSK group of companies, during the conduct of the study. S. A. M. reports payments from the GSK group of companies, during the conduct of the study; and reports payments from Pfizer, Merck, Novartis, and Sanofi, outside the submitted work. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The Global Influenza Hospital Surveillance Network (GIHSN) was established in 2012 to conduct coordinated worldwide influenza surveillance. In this study, we describe underlying comorbidities, symptoms, and outcomes in patients hospitalized with influenza., Methods: Between November 2018 and October 2019, GIHSN included 19 sites in 18 countries using a standardized surveillance protocol. Influenza infection was laboratory-confirmed with reverse-transcription polymerase chain reaction. A multivariate logistic regression model was utilized to analyze the extent to which various risk factors predict severe outcomes., Results: Of 16 022 enrolled patients, 21.9% had laboratory-confirmed influenza; 49.2% of influenza cases were A/H1N1pdm09. Fever and cough were the most common symptoms, although they decreased with age ( P < .001). Shortness of breath was uncommon among those <50 years but increased with age ( P < .001). Middle and older age and history of underlying diabetes or chronic obstructive pulmonary disease were associated with increased odds of death and intensive care unit (ICU) admission, and male sex and influenza vaccination were associated with lower odds. The ICU admissions and mortality occurred across the age spectrum., Conclusions: Both virus and host factors contributed to influenza burden. We identified age differences in comorbidities, presenting symptoms, and adverse clinical outcomes among those hospitalized with influenza and benefit from influenza vaccination in protecting against adverse clinical outcomes. The GIHSN provides an ongoing platform for global understanding of hospitalized influenza illness., Competing Interests: Potential conflicts of interest. MKA reports honoraria for advisory activities from Pfizer, Sanofi, and Seqirus and grant funding from Sanofi, GSK, Pfizer, Canadian Frailty Network, and Canadian Institutes of Health Research, unrelated to the current study. HP reports grant funding from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. SSC works for Sanofi when not seconded to the Foundation for Influenza Epidemiology. GD reports research grant funding to his institution from Pfizer, Sanofi, and MSD and honoraria from Pfizer, MSD, Sanofi. MCN reports grants from the Bill & Melinda Gates Foundation, European & Developing Countries Clinical Trials Partnership, Pfizer, AstraZeneca, and Sanofi, and honoraria for advisory activities from Sanofi. JRO reports that his institution has received research grants from Pfizer and National Institutes of Health for vaccine research, and he has received honoraria for advisory activities from GSK, Moderna, Pfizer, and Seqirus, outside the submitted work. SM reports honoraria and consulting fees from Sanofi and GlaxoSmithKline. PV reports honoraria from Pfizer. JP and LS report grant funding from Sanofi Pasteur, unrelated to the current work. HIGG and SMR report conference attendance funding from Sanofi. SAM reports grant and clinical trials funding from GSK, Merck, Pfizer, and Sanofi and payments from GSK, Pfizer, Sanofi, and Merck outside the submitted work. Acd reports grant funding from the EU/EFPIA Innovative medicine Initiative 2 Joint Undertaking (DRIVE Grant Number 777363). TZ reports grants from Pfizer and MSD. BL serves as chair of the scientific committee of Immuniser Lyon and co-chair of the Global Influenza Initiative. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Understanding the burden of influenza is necessary to optimize recommendations for influenza vaccination. We describe the epidemiology of severe influenza in 50- to 64-year-old residents of metropolitan Toronto and Peel region, Canada, over 7 influenza seasons., Methods: Prospective population-based surveillance for hospitalization associated with laboratory-confirmed influenza was conducted from September 2010 to August 2017. Conditions increasing risk of influenza complications were as defined by Canada's National Advisory Committee on Immunization. Age-specific prevalence of medical conditions was estimated using Ontario health administrative data. Population rates were estimated using Statistics Canada data., Results: Over 7 seasons, 1228 hospitalizations occurred in patients aged 50-64 years: 40% due to A(H3N2), 30% A(H1N1), and 22% influenza B. The average annual hospitalization rate was 15.6, 20.9, and 33.2 per 100 000 in patients aged 50-54, 55-59, and 60-64 years, respectively; average annual mortality was 0.9/100 000. Overall, 33% of patients had received current season influenza vaccine; 963 (86%) had ≥1 underlying condition increasing influenza complication risk. The most common underlying medical conditions were chronic lung disease (38%) and diabetes mellitus (31%); 25% of patients were immunocompromised. The average annual hospitalization rate was 6.1/100 000 in those without and 41/100 000 in those with any underlying condition, and highest in those with renal disease or immunocompromise (138 and 281 per 100 000, respectively). The case fatality rate in hospitalized patients was 4.4%; median length of stay was 4 days (interquartile range, 2-8 days)., Conclusions: The burden of severe influenza in 50- to 64-year-olds remains significant despite our universal publicly funded vaccination program. These data may assist in improving estimates of the cost-effectiveness of new strategies to reduce this burden., Competing Interests: Potential conflicts of interest. S. A. M. reports grant and clinical trials funding from GSK, Merck, Pfizer and Sanofi, and payments from GSK, Pfizer, Sanofi, and Merck outside the submitted work. B. C. reports payments from Seqirus outside the submitted work. A. J. M. reports grant funding from Pfizer, Sanofi and Seqirus, and payments from GSK, Merck, Moderna, Pfizer, and Sanofi outside of the submitted work. All other authors report no potential conflicts., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Seasonal respiratory viral infections are associated with exacerbations and morbidity among patients with COPD. The real-world clinical outcomes associated with seasonal viral infections are less well established among hospitalized patients., Research Question: To estimate the association between seasonal respiratory viral infections, 30-day mortality, and intensive care unit (ICU) admission among hospitalized COPD patients., Study Design and Methods: We conducted an analysis of a national prospective multicenter cohort of COPD patients hospitalized with acute respiratory illness during winter seasons (2011-2015) in Canada. Nasopharyngeal swabs were performed on all patients at the onset of hospital admission for diagnosis of viral infection. Primary outcomes were 30-day mortality and ICU admissions. Secondary outcomes included invasive/non-invasive ventilation use., Results: Among 3931 hospitalized patients with COPD, 28.5% (1122/3931) were diagnosed with seasonal respiratory viral infection. Viral infection was associated with increased admission to ICU (OR 1.5, 95% CI 1.2-1.9) and need for mechanical ventilation (OR 1.9, 95% CI 1.4-2.5), but was not associated with mortality (OR 1.1, 95% CI 0.8-1.4). Patients with respiratory syncytial virus (RSV) were equally likely to require ICU admission (OR 1.09, 95% CI 0.67-1.78), and more likely to need non-invasive ventilation (OR 3.1; 95% CI 1.8-5.1) compared to patients with influenza., Interpretation: Our results suggest COPD patients requiring hospitalization for respiratory symptoms should routinely receive viral testing at admission, especially for RSV and influenza, to inform prognosis, clinical management, and infection control practices during winter seasons. Patients with COPD will be an important target population for newly developed RSV therapeutics., Clinical Trial Registration: ClinicalTrials.gov ID: NCT01517191., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: We report characteristics and outcomes of adults admitted to Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network hospitals with COVID-19 in 2020., Methods: Patients with laboratory-confirmed COVID-19 admitted to 11 sites in Ontario, Quebec, Alberta, and Nova Scotia up to December 31, 2020 were enrolled in this prospective observational cohort study. Measures included age, sex, demographics, housing, exposures, Clinical Frailty Scale, comorbidities; in addition, length of stay, intensive care unit (ICU) admission, mechanical ventilation, and survival were assessed. Descriptive analyses and multivariable logistic regressions were conducted., Results: Among 2,011 patients, mean age was 71.0 (range 19-105) years. 29.7% were admitted from assisted living or long-term care facilities. The full spectrum of frailty was represented in both younger and older age groups. 81.8% had at least one underlying comorbidity and 27.2% had obesity. Mortality was 14.3% without ICU admission, and 24.6% for those admitted to ICU. Older age and frailty were independent predictors of lower ICU use and higher mortality; accounting for frailty, obesity was not an independent predictor of mortality, and associations of comorbidities with mortality were weakened., Conclusions: Frailty is a critical clinical factor in predicting outcomes of COVID-19, which should be considered in research and clinical settings., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood the Canadian Geriatrics Journal’s policy on conflicts of interest disclosure and declare the following interests: MKA reports grant funding from the Public Health Association of Canada, CIHR, Canadian Frailty Network, Sanofi Pasteur and GSK group of companies, and payments from Pfizer, Sanofi Pasteur and Seqirus outside the submitted work. AM reports payments from GSK, Seqirus and Sanofi Pasteur, outside the submitted work. JEM reports payments from RestorBio, Sanofi, GSK, Merck and Medicago outside of the submitted work. TFH reports grants from Pfizer and GSK. ML reports payments from Sanofi, Medicago, Sequirus, and Pfizer outside the submitted work. SAM reports grants and payments from Pfizer, GSK, Merck, Novartis and Sanofi, outside the submitted work. JG, JJL, GB, LV, ME, DM-C, AA, KW, ST, SS, AMc and KK report no conflicts of interest., (© 2022 Author(s). Published by the Canadian Geriatrics Society.)

Objective(s): In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017., Methods: S. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16-49, 50-64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]., Results: 11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50-64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP., Conclusion(s): Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: MKA reports grants from the Canadian Frailty Network, CIHR, Public Health Agency of Canada, Sanofi, Pfizer, Merck and GSK, and payments from Pfizer, Sanofi and Seqirus outside the submitted work. SAM reports grants and payments from Pfizer, GSK, Merck, Novartis and Sanofi, outside the submitted work.

Background & Aims: Patients with inflammatory bowel disease (IBD) may be at increased risk of some vaccine-preventable diseases. The effectiveness and safety of vaccinations may be altered by immunosuppressive therapies or IBD itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on live vaccines., Methods: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative process and voted on by a multidisciplinary panel. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients., Results: Three good practice statements included reviewing a patient's vaccination status at diagnosis and at regular intervals, giving appropriate vaccinations as soon as possible, and not delaying urgently needed immunosuppressive therapy to provide vaccinations. There are 4 recommendations on the use of live vaccines. Measles, mumps, rubella vaccine is recommended for both adult and pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). Varicella vaccine is recommended for pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). For adults, recommendations are conditionally in favor of varicella vaccine for those not on immunosuppressive therapy, and against for those on therapy. No recommendation was made regarding the use of live vaccines in infants born to mothers using biologics because the desirable and undesirable effects were closely balanced and the evidence was insufficient., Conclusions: Maintaining appropriate vaccination status in patients with IBD is critical to optimize patient outcomes. In general, live vaccines are recommended in patients not on immunosuppressive therapy, but not for those using immunosuppressive medications. Additional studies are needed to evaluate the safety and efficacy of live vaccines in patients on immunosuppressive therapy., (Copyright © 2021. Published by Elsevier Inc.)

Background and Aims: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines., Methods: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients., Results: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years., Conclusions: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility., Methods: Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus., Findings: Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis., Competing Interests: Mary K. Foley – Ms. Foley has nothing to disclose. Samuel D. Searle - Dr. Searle received PhD and fellowship funding from the Canadian Frailty Network, Dalhousie Medical Research Foundation, Dalhousie University Internal Medicine Research Foundation and the QE II Innovation Fund. Ali Toloue – Toloue has nothing to disclose. Ryan Booth -Ryan Booth has nothing to disclose. Alec Falkenham – Dr. Falkenham has nothing to disclose. Darryl Falzarano – Dr. Falzarano has nothing to disclose. Salvatore Rubino – Dr. Rubino has nothing to disclose. Magen E. Francis – Ms. Francis has nothing to disclose. Mara McNeil – Ms. McNeil has nothing to disclose. Christopher Richardson – Dr. Richardson has nothing to disclose. Jason LeBlanc – Dr. LeBlanc has nothing to disclose. Sharon Oldford – Dr. Oldford has nothing to disclose. Volker Gerdts – Dr. Gerdts has nothing to disclose. Melissa K. Andrew – Dr. Andrew reports grants from Sanofi, grants from GSK, grants from Pfizer, grants from Canadian Frailty Network, grants from CIHR, grans from Public Health Agency of Canada, personal fees from Sanofi, from Pfizer, personal fees from Seqirus, outside the submitted work. Shelly A. McNeil – Dr. McNeil reports grants, personal fees and other from Pfizer, other from Medicago, personal fees and other from Sanofi, grants, personal fees and other from GlaxoSmithKline, grants personal fees and other from Merck, other from CanSino, other from IMV, other from Janssen, outside the submitted work. Barry Clarke – Dr. Clarke has nothing to disclose. Kenneth Rockwood – Dr. Rockwood reports personal fees from Clinical Cardio Day – Cape Breton University, personal fees from CRUIGM-Montreal, from Speaker at Jackson Lab, Bar Harbor MA, personal fees from Speaker at MouseAge Rome Italy, personal fees from Frontemporal Dementia Study Group, personal fees from SunLife Insurance Japan, outside the submitted work and Kenneth Rockwood is President and Co-founder of Ardea Outcomes, which in the last three years (as DGI Clinical) has contracts with pharma and device manufacturers (Shire, Hollister, Nutricia, Roche, Otsuka) on individualized outcome measurement. Otherwise any personal fees are for invited guest lectures and academic symposia, received directly from event organizers, chiefly for presentations on frailty. He is Associate Director of the Canadian Consortium on Neurodegeneration in Aging, which is funded by the Canadian Institutes of Health Research, and with additional funding from the Alzheimer Society of Canada and several other charities. He receives career support from the Dalhousie Medical Research Foundation as the Kathryn Allen Weldon Professor of Alzheimer Research, and research support from the Canadian Institutes of Health Research, The Canadian Frailty Network, the QEII Health Science centre Foundation, the Nova Scotia Health Research Fund and the Fountain Family Innovation Fund of the QEII Health Science centre Foundation. David J. Kelvin – Dr. Kelvin has nothing to disclose. Alyson A. Kelvin – Dr. A. Kelvin has nothing to disclose., (© 2021 The Authors.)

Background: In 2017, the two-dose recombinant zoster vaccine (RZV) was authorized for use in Canada for the prevention of herpes zoster (HZ) in adults ≥ 50 years of age (YOA), which is administered 2-6 months apart. The National Advisory Committee on Immunization (NACI) states that a 0, 12-month schedule may be considered if flexibility in the timing of the second dose is needed to improve coverage. This retrospective database study evaluated the second-dose completion of RZV in Canada from January 2018 to May 2019., Methods: Data were obtained from the IQVIA LRx Longitudinal Prescription Database which tracks retail prescriptions of anonymized patients. Patients were followed for 6- or 12-months to evaluate the second dose completion aligned with the licensed RZV dosing schedule and NACI's option for greater flexibility. The primary outcomes were time from first to second dose and the proportion of patients who received the second dose., Results: In the 6-month (155,747 patients) and 12-month (55,524 patients) analytic cohorts, 65.0% and 74.9% received the second RZV dose within 2-6 months and 2-12 months after the first dose with a truncated mean time of 97.8 days and 109.8 days between doses, respectively. Variation in completion rates was observed across age and geography, but sex, rurality, and pharmacy type did not impact results., Conclusion: Second dose completion of RZV in Canada is high but suboptimal. Further research to understand the factors influencing second dose timing and completion will be an important next step to improve series completion., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Ashleigh McGirr and Michael Wortzman are employees and hold shares of the GSK Group of Companies. Shelly A. McNeil reports grants, personal fees and other from GSK, personal fees and other from Merck, grants, personal fees and other from Pfizer and Sanofi, outside the submitted work. Tara Bourgoin and Brad Millson are employed by IQVIA which was contracted by GSK to conduct the study related to the present work.], (Copyright © 2021 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.)

Older adults are at high risk from influenza and its complications, and are therefore an important population for prevention efforts. In Canada, public health efforts targeting influenza are multi-pronged and include vaccination programs as well as surveillance which informs the national surveillance reporting platform FluWatch run by the Public Health Agency of Canada. Recommendations regarding use of vaccines are made nationally by the National Advisory Committee on Immunization (NACI) and by the Comité sur l'immunisation du Québec in Quebec, while vaccination programs are planned and delivered at the provincial/territorial level as opposed to as a harmonized national immunization program. NACI performs rigorous targeted literature reviews to inform their statements, and recommendations also vary by whether they apply on Individual (pertaining to decisions for individual patients) vs. Programmatic (informing policy decisions for implementation of publicly funded vaccination programs) levels. This unique context results in inter-provincial variation in vaccine schedules and funded vaccine products. In this paper, the importance of influenza vaccination for older adults is discussed; to provide insights from the Canadian context, the evolution of NACI evidence reviews and recommendations on influenza vaccination is presented., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: No funding or payment was involved in the preparation of this review. MKA and SAM report grant funding from the Public Health Agency of Canada through Service Canada, Canadian Institutes of Health Research, and Canadian Immunization Research Network in the conduct of the Serious Outcomes Surveillance Network. MKA reports grant funding from the Canadian Frailty Network, Sanofi, GSK, and Pfizer, and payments from Sanofi and Pfizer outside the submitted work. SAM reports grant and clinical trials funding from GSK, Merck, Pfizer and Sanofi, and payments from GSK, Pfizer, Sanofi and Merck outside the submitted work., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background/objectives: Frail participants are often under-represented in randomized trials, raising questions about outcomes of interventions in real-world settings. Frailty is strongly associated with vulnerability to illness and adverse health outcomes. We studied the impact of frailty on recombinant zoster vaccine (RZV) clinical outcomes., Design/setting: Data from two previously conducted phase III randomized trials of RZV were pooled. These two parent trials were conducted concurrently at the same study sites using the same methods., Participants/intervention: In the two parent studies, participants aged ≥50 years (ZOE-50 study) and ≥70 years (ZOE-70 study), respectively, were randomized 1:1 to receive two doses of RZV or placebo., Measurements: In the current ZOE-Frailty study (NCT03563183), a frailty index was created using previously validated methods. Clinical outcomes assessed by frailty status included vaccine efficacy, immunogenicity, reactogenicity, and safety., Results: Of 29,305 participants from the pooled ZOE-50 and ZOE-70 total vaccinated cohort, 92% were included in this study. Mean age was 68.8 years; 58.1% were women; 45.6% were pre-frail and 11.3% frail. The percentage of frail participants increased with age from 5.7% aged 50-59 years to 22.7% aged ≥80 years. RZV vaccine efficacy against herpes zoster was >90% for all frailty subgroups (non-frail: 95.8% (95% confidence interval = 91.6-98.2), pre-frail: 90.4% (84.4-94.4), frail: 90.2% (75.4-97.0)). The RZV group demonstrated robust anti-gE antibody and gE-specific CD4 2+ responses, with mean concentrations remaining above pre-vaccination levels at least 3 years post-dose two, in all frailty subgroups. In the RZV group, the percentage of participants reporting solicited adverse events tended to decrease with increasing frailty., Conclusion: The relatively nonrestrictive inclusion/exclusion criteria in the parent ZOE studies resulted in a range of participants that included frail and pre-frail older adults. RZV significantly reduced the risk of herpes zoster across all frailty subgroups., (© 2020 The Authors Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background/objectives: Influenza is associated with significant morbidity and mortality, particularly for older adults. Persistent functional decline following hospitalization has important impacts on older adults' wellbeing and independence, but has been under-studied in relation to influenza. We aimed to investigate persistent functional change in older adults admitted to hospital with influenza and other acute respiratory illness (ARI)., Design: Protective observational cohort study., Setting: Canadian Immunization Research Network Serious Outcomes Surveillance Network 2011 to 2012 influenza season., Participants: A total of 925 patients aged 65 and older admitted to hospital with influenza and other ARI., Measurements: Influenza was laboratory-confirmed. Frailty was measured using a Frailty index (FI). Functional status was measured using the Barthel index (BI); moderate persistent functional decline was defined as a clinically meaningful loss of ≥10 to <20 points on the 100-point BI. Catastrophic disability (CD) was defined as a loss of ≥20 points, equivalent to full loss of independence in two basic activities of daily living., Results: Five hundred and nineteen (56.1%) were women; mean age was 79.4 (standard deviation=8.4) years. Three hundred and forty-six (37.4%) had laboratory-confirmed influenza. Influenza cases had lower baseline function (BI = 77.0 vs 86.9, P < .001) and higher frailty (FI = 0.23 vs 0.20, P < .001) than those with other ARI. A total of 8.4% died, 8.2% experienced persistent moderate functional decline, and 9.9% experienced CD. Higher baseline frailty was associated with increased odds of experiencing functional decline, CD, and death. The experience of functional decline and CD, and its association with frailty, was the same for influenza and other ARI., Conclusion: Functional loss in hospital is common among older adults; for some this functional loss is persistent and catastrophic. This highlights the importance of prevention and optimal management of acute declines in health, including influenza, to avoid hospitalization. In the case of influenza, for which vaccines exist, this raises the potential of vaccine preventable disability., (© 2021 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: Clinically meaningful change (CMC) for frailty index (FI) scores is little studied. We estimated the CMC by associating changes in FI scores with changes in the Clinical Frailty Scale (CFS) in hospitalized patients., Methods: The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network enrolled older adults (65+ years) admitted to hospital with acute respiratory illness (mean age = 79.6 ± 8.4 years; 52.7% female). Patients were assigned CFS and 39-item FI scores in-person at admission and via telephone at 1-month postdischarge. Baseline frailty state was assessed at admission using health status 2 weeks before admission. We classified those whose CFS scores remained unchanged (n = 1,534) or increased (n = 4,390) from baseline to hospital admission, and whose CFS scores remained unchanged (n = 1,565) or decreased (n = 2,546) from admission to postdischarge. For each group, the CMC was represented as the FI score change value that best predicted one level CFS change, having the largest Youden J value in comparison to no change., Results: From baseline to admission, 74.1% increased CFS by ≥1 level. From admission to postdischarge, 61.9% decreased CFS by ≥1 levels. A change in FI score of 0.03 best predicted both one-level CFS increase (sensitivity = 70%; specificity = 69%) and decrease (sensitivity = 66%; specificity = 61%) in comparison to no change. Of those who changed CFS by ≥1 levels, 70.9% (baseline to admission) and 72.4% (admission to postdischarge) changed their FI score by at least 0.03., Conclusions: A clinically meaningful change of 0.03 in the frailty index score holds promise as a benchmark for assessing the meaningfulness of frailty interventions., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We examined frailty as a predictor of recovery in older adults hospitalized with influenza and acute respiratory illness., Methods: A total of 5011 patients aged ≥65 years were admitted to Canadian Serious Outcomes Surveillance Network hospitals during the 2011/2012, 2012/2013, and 2013/2014 influenza seasons. Frailty was measured using a previously validated frailty index (FI). Poor recovery was defined as death by 30 days postdischarge or an increase of more than 0.06 (≥2 persistent new health deficits) on the FI. Multivariable logistic regression controlled for age, sex, season, influenza diagnosis, and influenza vaccination status., Results: Mean age was 79.4 (standard deviation = 8.4) years; 53.1% were women. At baseline, 15.0% (n = 750) were nonfrail, 39.3% (n = 1971) were prefrail, 39.8% (n = 1995) were frail, and 5.9% (n = 295) were most frail. Poor recovery was experienced by 21.4%, 52.0% of whom had died. Frailty was associated with lower odds of recovery in all 3 seasons: 2011/2012 (odds ratio [OR] = 0.70; 95% confidence interval [CI], 0.59-0.84), 2012/2013 (OR = 0.72; 95% CI, 0.66-0.79), and 2013/2014 (OR = 0.75; 95% CI, 0.69-0.82); results varied by season, influenza status, vaccination status, and age., Conclusions: Increasing frailty is associated with lower odds of recovery, and persistent worsening frailty is an important adverse outcome of acute illness., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Since 2011, the Global Influenza Hospital Surveillance Network (GIHSN) has used active surveillance to prospectively collect epidemiological and virological data on patients hospitalized with influenza virus infection. Here, we describe influenza virus strain circulation in the GIHSN participant countries during 2017-2018 season and examine factors associated with complicated hospitalization among patients admitted with laboratory-confirmed influenza illness., Methods: The study enrolled patients who were hospitalized in a GIHSN hospital in the previous 48 h with acute respiratory symptoms and who had symptoms consistent with influenza within the 7 days before admission. Enrolled patients were tested by reverse transcription-polymerase chain reaction to confirm influenza virus infection. "Complicated hospitalization" was defined as a need for mechanical ventilation, admission to an intensive care unit, or in-hospital death. In each of four age strata (< 15, 15-< 50, 50-< 65, and ≥ 65 years), factors associated with complicated hospitalization in influenza-positive patients were identified by mixed effects logistic regression and those associated with length of hospital stay using a linear mixed-effects regression model., Results: The study included 12,803 hospitalized patients at 14 coordinating sites in 13 countries, of which 4306 (34%) tested positive for influenza. Influenza viruses B/Yamagata, A/H3N2, and A/H1N1pdm09 strains dominated and cocirculated, although the dominant strains varied between sites. Complicated hospitalization occurred in 10.6% of influenza-positive patients. Factors associated with complicated hospitalization in influenza-positive patients included chronic obstructive pulmonary disease (15-< 50 years and ≥ 65 years), diabetes (15-< 50 years), male sex (50-< 65 years), hospitalization during the last 12 months (50-< 65 years), and current smoking (≥65 years). Chronic obstructive pulmonary disease (50-< 65 years), other chronic conditions (15-< 50 years), influenza A (50-< 65 years), and hospitalization during the last 12 months (< 15 years) were associated with a longer hospital stay. The proportion of patients with complicated influenza did not differ between influenza A and B., Conclusions: Complicated hospitalizations occurred in over 10% of patients hospitalized with influenza virus infection. Factors commonly associated with complicated or longer hospitalization differed by age group but commonly included chronic obstructive pulmonary disease, diabetes, and hospitalization during the last 12 months.

Compared to the standard two-tiered testing (STTT) algorithm for Lyme disease serology using an enzyme immunoassay (EIA) followed by Western blotting, data from the United States suggest that a modified two-tiered testing (MTTT) algorithm employing two EIAs has improved sensitivity to detect early localized Borrelia burgdorferi infections without compromising specificity. From 2011 to 2014, in the Canadian province of Nova Scotia, where Lyme disease is hyperendemic, sera submitted for Lyme disease testing were subjected to a whole-cell EIA, followed by C6 EIA and subsequently IgM and/or IgG immunoblots on sera with EIA-positive or equivocal results. Here, we evaluate the effectiveness of the MTTT algorithm compared to the STTT approach in a Nova Scotian population. Retrospective chart reviews were performed on patients testing positive with the whole-cell and C6 EIAs (i.e., the MTTT algorithm). Patients were classified as having Lyme disease if they had a positive STTT result, a negative STTT result but symptoms consistent with Lyme disease, or evidence of seroconversion on paired specimens. Of the 10,253 specimens tested for Lyme disease serology, 9,806 (95.6%) were negative. Of 447 patients who tested positive, 271 charts were available for review, and 227 were classified as patients with Lyme disease. The MTTT algorithm detected 25% more early infections with a specificity of 99.56% (99.41 to 99.68%) compared to the STTT. These are the first Canadian data to show that serology using a whole-cell sonicate EIA followed by a C6 EIA (MTTT) had improved sensitivity for detecting early B. burgdorferi infection with specificity similar to that of two-tiered testing using Western blots., (Copyright © 2020 American Society for Microbiology.)

Older adults have been disproportionately affected by the COVID-19 pandemic, with many outbreaks occurring in Long Term Care Facilities (LTCFs). We discuss this vulnerability among LTCF residents using an ecological framework, on levels spanning from the individual to families and caregivers, institutions, health services and systems, communities, and contextual government policies. Challenges abound for fully understanding the burden of COVID-19 in LTCF, including differences in nomenclature, data collection systems, cultural differences, varied social welfare models, and (often) under-resourcing of the LTC sector. Registration of cases and deaths may be limited by testing capacity and policy, record-keeping and reporting procedures. Hospitalization and death rates may be inaccurate depending on atypical presentations and whether or not residents' goals of care include escalation of care and transfer to hospital. Given the important contribution of frailty, use of the Clinical Frailty Scale (CFS) is discussed as a readily implementable measure, as are lessons learned from the study of frailty in relation to influenza. Biomarkers hold emerging promise in helping to predict disease severity and address the puzzle of why some frail LTCF residents are resilient to COVID-19, either remaining test-negative despite exposure or having asymptomatic infection, while others experience the full range of illness severity including critical illness and death. Strong and coordinated surveillance and research focused on LTCFs and their frail residents is required. These efforts should include widespread assessment of frailty using feasible and readily implementable tools such as the CFS, and rigorous reporting of morbidity and mortality in LTCFs., Competing Interests: MKA and SAM report grant funding from the Public Health Agency of Canada through Service Canada, Canadian Institutes of Health Research, and Canadian Immunization Research Network in the conduct of the Serious Outcomes Surveillance Network. MKA reports funding and honoraria from the Canadian Frailty Network, Sanofi, GSK, and Pfizer outside the submitted work. JEM’s institution has received honoraria for consultancies with GSK, Sanofi, Merck, Pfizer, Medicago and RestorBio, outside of the submitted work. SAM reports funding and honoraria from GSK, Merck, Pfizer and Sanofi outside the submitted work. KR founded and is Chief Science Officer of DGI Clinical, which has several contracts with pharma and medical device manufacturers. He developed the CFS and has asserted copyright through Dalhousie University; it is made available for free clinical and academic use including through a downloadable App. SDS, BC and DJK report no conflict of interest, (Copyright (c) 2020 Melissa Andrew, Samuel D Searle, Janet E McElhaney, Shelly A McNeil, Barry Clarke, Kenneth Rockwood, David J Kelvin.)

Objective: Older adults often have atypical presentation of illness and are particularly vulnerable to influenza and its sequelae, making the validity of influenza case definitions particularly relevant. We sought to assess the performance of influenza-like illness (ILI) and severe acute respiratory illness (SARI) criteria in hospitalized older adults., Design: Prospective cohort study., Setting: The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network undertakes active surveillance for influenza among hospitalized adults., Methods: Data were pooled from 3 influenza seasons: 2011/12, 2012/13, and 2013/14. The ILI and SARI criteria were defined clinically, and influenza was laboratory confirmed. Frailty was measured using a validated frailty index., Results: Of 11,379 adult inpatients (7,254 aged ≥65 years), 4,942 (2,948 aged ≥65 years) had laboratory-confirmed influenza. Their median age was 72 years (interquartile range [IQR], 58-82) and 52.6% were women. The sensitivity of ILI criteria was 51.1% (95% confidence interval [CI], 49.6-52.6) for younger adults versus 44.6% (95% CI, 43.6-45.8) for older adults. SARI criteria were met by 64.1% (95% CI, 62.7-65.6) of younger adults versus 57.1% (95% CI, 55.9-58.2) of older adults with laboratory-confirmed influenza. Patients with influenza who were prefrail or frail were less likely to meet ILI and SARI case definitions., Conclusions: A substantial proportion of older adults, particularly those who are frail, are missed by standard ILI and SARI case definitions. Surveillance using these case definitions is biased toward identifying younger cases, and does not capture the true burden of influenza. Because of the substantial fraction of cases missed, surveillance definitions should not be used to guide diagnosis and clinical management of influenza.

Background: Viral respiratory illnesses are common causes of outbreaks and can be fatal to some patients., Aim: To investigate the association between laboratory-confirmed viral respiratory infections and potential sources of exposure during the previous 7 days., Methods: In this nested case-control analysis, healthcare personnel from nine Canadian hospitals who developed acute respiratory illnesses during the winters of 2010/11-2013/14 submitted swabs that were tested for viral pathogens. Associated illness diaries and the weekly diaries of non-ill participants provided information on contact with people displaying symptoms of acute respiratory illness in the previous week. Conditional logistic regression assessed the association between cases, who were matched by study week and site with controls with no respiratory symptoms., Findings: There were 814 laboratory-confirmed viral respiratory illnesses. The adjusted odds ratio (aOR) of a viral illness was higher for healthcare personnel reporting exposures to ill household members [7.0, 95% confidence interval (CI) 5.4-9.1], co-workers (3.4, 95% CI 2.4-4.7) or other social contacts (5.1, 95% CI 3.6-7.1). Exposures to patients with respiratory illness were not associated with infection (aOR 0.9, 95% CI 0.7-1.2); however, healthcare personnel with direct patient contact did have higher odds (aOR 1.3, 95% CI 1.1-1.6). The aORs for exposure and for direct patient contact were similar for illnesses caused by influenza., Conclusion: Community and co-worker contacts are important sources of viral respiratory illness in healthcare personnel, while exposure to patients with recognized respiratory infections is not associated. The comparatively low risk associated with direct patient contact may reflect transmission related to asymptomatic patients or unrecognized infections., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Emergency vaccination programs often are needed to control outbreaks of meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) on college campuses. Such campaigns expend multiple campus and public health resources. We conducted a randomized, controlled, multicenter, observer-blinded trial comparing immunogenicity and tolerability of an accelerated vaccine schedule of 0 and 21 days to a longer interval of 0 and 60 days for 4-component MenB vaccine (MenB-4C) in students 17-25 years of age. At day 21 after the first MenB-4C dose, we observed protective human serum bactericidal titers >4 to MenB strains 5/99, H44/76, and NZ 98/254 in 98%-100% of participants. Geometric mean titers increased >22-fold over baseline. At day 180, >95% of participants sustained protective titers regardless of their vaccine schedule. The most common adverse event was injection site pain. An accelerated MenB-4C immunization schedule could be considered for rapid control of campus outbreaks.

Background: In Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age., Methods: Surveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16-49, 50-64, ≥65 and ≥50 years)., Results: Of 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively., Conclusions: Adults hospitalised with pCAP in the age cohort of 50-64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada., Competing Interests: Competing interests: SAM received research grants and personal fees from GlaxoSmithKline, Pfizer and Sanofi Pasteur and personal fees from Merck; JL and TH participated on investigator-initiated grants sponsored by GSK and Pfizer; JL received grants from Merck; LV received research grants from GlaxoSmithKline, Pfizer, Optimer, Cubist and Merck, and personal fees from Merck, Optimer and Cubist. ML received grants from Pfizer. CL was a former employee for Pfizer Canada, Kirkland Québec, Québec. No other conflicts were declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Streptococcus pyogenes (group A Streptococcus, Strep A) is a widespread pathogen that continues to pose a significant threat to human health. The development of a Strep A vaccine remains an unmet global health need. One of the major vaccine strategies is the use of M protein, which is a primary virulence determinant and protective antigen. Multivalent recombinant M protein vaccines are being developed with N-terminal M peptides that contain opsonic epitopes but do not contain human tissue cross-reactive epitopes., Methods: We completed a Phase I trial of a recombinant 30-valent M protein-based Strep A vaccine (Strep A vaccine, StreptAnova™) comprised of four recombinant proteins containing N-terminal peptides from 30 M proteins of common pharyngitis and invasive and/or rheumatogenic serotypes, adjuvanted with aluminum hydroxide. The trial was observer-blinded and randomized in a 2:1 ratio for intramuscular administration of Strep A vaccine or an alum-based comparator in healthy adult volunteers, at 0, 30 and 180 days. Primary outcome measures were assessments of safety, including assays for antibodies that cross-reacted with host tissues, and immunogenicity assessed by ELISA with the individual vaccine peptides and by opsonophagocytic killing (OPK) assays in human blood., Results: Twenty-three Strep A-vaccinated participants and 13 controls completed the study. The Strep A vaccine was well-tolerated and there was no clinical evidence of autoimmunity and no laboratory evidence of tissue cross-reactive antibodies. The vaccine was immunogenic and elicited significant increases in geometric mean antibody levels to 24 of the 30 component M antigens by ELISA. Vaccine-induced OPK activity was observed against selected M types of Strep A in vaccinated participants that seroconverted to specific M peptides., Conclusion: The Strep A vaccine was well tolerated and immunogenic in healthy adults, providing strong support for further clinical development. [ClinicalTrials.gov NCT02564237]., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elodie Pastural is a former project manager for PREVENT, a funder of the study. Luis H. Martin is a former officer of PREVENT. Scott Halperin is a member of the Board of Directors of PREVENT. James B. Dale is an inventor on patent applications licensed to, and owns shares of, Vaxent, a funder of the study. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Background . The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed. Methods . Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses. Results . In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages. Conclusions . Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

Background: The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy., Methods: In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1-2 months (M) apart 4-18M posttransplant. Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post-dose 1, and 1M and 12M post-dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post-dose 2., Results: Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post-dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups., Conclusions: RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose., Clinical Trials Registration: NCT02058589., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Increased susceptibility to the serious complications of influenza is common in older adults. It is often ascribed to weakening of the immune system with age, and 90% of influenza-related deaths occur in older adults despite widespread vaccination programs. Common chronic conditions not only contribute to the loss of immune protection after vaccination and increase the risk for serious outcomes of influenza, but also increase the long-term consequences following hospitalization. Interactions of T and B cell ageing, chronic elevation of inflammatory cytokines (sometimes dubbed "inflammaging"), and dysregulated acute cytokine production pose major challenges to the development of new and more effective vaccines. However, these age-related problems are modifiable, as we have shown, and provide a clear margin for improvement. This chapter describes how an exclusive focus on developing influenza vaccines to stimulate strain-specific antibody responses against the hemagglutinin surface glycoprotein of the influenza virus, to the exclusion of other potentially important mechanisms, is missing the mark in terms of preventing the serious complications of influenza in older adults. Novel approaches are needed to enhance antibody-mediated protection against infection and stimulate cell-mediated immune responses to clear influenza virus from the lungs. These strategies for improving vaccine effectiveness will address the public health need for "vaccine prevention of disability" to mitigate the global pressures of aging populations on health and social care systems., (© 2020 S. Karger AG, Basel.)

Background: The adjuvanted recombinant zoster vaccine (Shingrix) can prevent herpes zoster in older adults and autologous haemopoietic stem cell transplant recipients. We evaluated the safety and immunogenicity of this vaccine in adults with haematological malignancies receiving immunosuppressive cancer treatments., Methods: In this phase 3, randomised, observer-blind, placebo-controlled study, done at 77 centres worldwide, we randomly assigned (1:1) patients with haematological malignancies aged 18 years and older to receive two doses of the adjuvanted recombinant zoster vaccine or placebo 1-2 months apart during or after immunosuppressive cancer treatments, and stratified participants according to their underlying diseases. The co-primary objectives of the study were the evaluation of safety and reactogenicity of the adjuvanted recombinant zoster vaccine compared with placebo from the first vaccination up to 30 days after last vaccination in all participants; evaluation of the proportion of participants with a vaccine response in terms of anti-glycoprotein E humoral immune response to the adjuvanted recombinant zoster vaccine at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia; and evaluation of the anti-glycoprotein E humoral immune responses to the vaccine compared with placebo at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. We assessed immunogenicity in the per-protocol cohort for immunogenicity and safety in the total vaccinated cohort. The study is registered with ClinicalTrials.gov, number NCT01767467, and with the EU Clinical Trials Register, number 2012-003438-18., Findings: Between March 1, 2013, and Sept 10, 2015, we randomly assigned 286 participants to adjuvanted recombinant zoster vaccine and 283 to placebo. 283 in the vaccine group and 279 in the placebo group were vaccinated. At month 2, 119 (80·4%, 95% CI 73·1-86·5) of 148 participants had a humoral vaccine response to adjuvanted recombinant zoster vaccine, compared with one (0·8%, 0·0-4·2) of 130 participants in the placebo group, and the adjusted geometric mean anti-glycoprotein E antibody concentration was 23 132·9 mIU/mL (95% CI 16 642·8-32 153·9) in the vaccine group and 777·6 mIU/mL (702·8-860·3) in the placebo group (adjusted geometric mean ratio 29·75, 21·09-41·96; p<0·0001) in all patients, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. Humoral and cell-mediated immune responses persisted above baseline until month 13 in all strata and, as expected, vaccine was more reactogenic than placebo (within 7 days after vaccination pain was reported by 221 [79·5%] of 278 vaccine group participants and 45 [16·4%] of 274 placebo group participants; fatigue was reported by 162 [58·3%] of 278 vaccine group participants and 102 [37·2%] of 274 placebo group participants). Incidences of unsolicited or serious adverse events, potential immune-mediated diseases, disease-related events, and fatal serious adverse events were similar between the groups., Interpretation: The immunocompromised adult population with haematological malignancies is at high risk for herpes zoster. The adjuvanted recombinant zoster vaccine, which is currently licensed in certain countries for adults aged 50 years and older, is likely to benefit this population., Funding: GlaxoSmithKline Biologicals SA., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Patients who are immunocompromised because of malignancy have an increased risk of herpes zoster and herpes zoster-related complications. We aimed to investigate the efficacy and safety of an inactivated varicella zoster virus (VZV) vaccine for herpes zoster prevention in patients with solid tumour or haematological malignancies., Methods: This phase 3, two-arm, randomised, double-blind, placebo-controlled, multicentre trial with an adaptive design was done in 329 centres across 40 countries. The trial included adult patients with solid tumour malignancies receiving chemotherapy and those with haematological malignancies, either receiving or not receiving chemotherapy. Patients were randomly assigned (1:1) to receive four doses of VZV vaccine inactivated by γ irradiation or placebo approximately 30 days apart. The patients, investigators, trial site staff, clinical adjudication committee, and sponsor's clinical and laboratory personnel were masked to the group assignment. The primary efficacy endpoint was herpes zoster incidence in patients with solid tumour malignancies receiving chemotherapy, which was assessed in the modified intention-to-treat population (defined as all randomly assigned patients who received at least one dose of inactivated VZV vaccine or placebo). The primary safety endpoint was serious adverse events up to 28 days after the fourth dose in patients with solid tumour malignancies receiving chemotherapy. Safety endpoints were assessed in all patients who received at least one dose of inactivated VZV vaccine or placebo and had follow-up data. This trial is registered (NCT01254630 and EudraCT 2010-023156-89)., Findings: Between June 27, 2011, and April 11, 2017, 5286 patients were randomly assigned to receive VZV vaccine inactivated by γ irradiation (n=2637) or placebo (n=2649). The haematological malignancy arm was terminated early because of evidence of futility at a planned interim analysis; therefore, all prespecified haematological malignancy endpoints were deemed exploratory. In patients with solid tumour malignancies in the modified intention-to-treat population, confirmed herpes zoster occurred in 22 of 1328 (6·7 per 1000 person-years) VZV vaccine recipients and in 61 of 1350 (18·5 per 1000 person-years) placebo recipients. Estimated vaccine efficacy against herpes zoster in patients with solid tumour malignancies was 63·6% (97·5% CI 36·4 to 79·1), meeting the prespecified success criterion. In patients with solid tumour malignancies, serious adverse events were similar in frequency across treatment groups, occurring in 298 (22·5%) of 1322 patients who received the vaccine and in 283 (21·0%) of 1346 patients who received placebo (risk difference 1·5%, 95% CI -1·7 to 4·6). Vaccine-related serious adverse events were less than 1% in each treatment group. Vaccine-related injection-site reactions were more common in the vaccine group than in the placebo group. In the haematological malignancy group, VZV vaccine was well tolerated and estimated vaccine efficacy against herpes zoster was 16·8% (95% CI -17·8 to 41·3)., Interpretation: The inactivated VZV vaccine was well tolerated and efficacious for herpes zoster prevention in patients with solid tumour malignancies receiving chemotherapy, but was not efficacious for herpes zoster prevention in patients with haematological malignancies., Funding: Merck & Co, Inc., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011-2012 through 2014-2015) in Canada., Methods: Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B)., Results: Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012-2013 and 2014-2015. Conversely, in 2011-2012, during which B viruses circulated, and in 2013-2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype., Conclusions: Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults., Clinical Trials Registration: NCT01517191., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)