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The detection of Clostridioides difficile infections (CDI) relies on testing the stool of patients by toxin antigen detection or PCR methods. Although PCR and antigenic methods have significantly reduced the time to results, delays in stool collection can significantly add to the turnaround time. The use of rectal swabs to detect C. difficile could considerably reduce the time to diagnosis of CDI. We developed a new rapid PCR assay for the detection of C. difficile and evaluated this PCR assay on both stool and rectal swab specimens. We recruited a total of 623 patients suspected of C. difficile infection. Stool samples and rectal swabs were collected from each patient and tested by our PCR assay. Stool samples were also tested by the cell cytotoxicity neutralization assay (CCNA) as a reference. The PCR assay detected C. difficile in 60 stool specimens and 61 rectal swabs for the 64 patients whose stool samples were positive for C. difficile by CCNA. The PCR assay detected an additional 35 and 36 stool and rectal swab specimens positive for C. difficile , respectively, for sensitivity with stools and rectal swabs of 93.8% and 95.3%, specificity of 93.7% and 93.6%, positive predictive values of 63.2% and 62.9%, and negative predictive values of 99.2% and 99.4%. Detection of C. difficile using PCR on stools or rectal swabs yielded reliable and similar results. The use of PCR tests on rectal swabs could reduce turnaround time for CDI detection, thus improving CDI management and control of C. difficile transmission., Importance: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, resulting in high morbidity, mortality, and economic burden. In clinical laboratories, CDI testing is currently performed on stool samples collected from patients with diarrhea. However, the diagnosis of CDI can be delayed by the time required to collect stool samples. Barriers to sample collection could be overcome by using a rectal swab instead of a stool sample. Our study showed that CDI can be identified rapidly and reliably by a new PCR assay developed in our laboratory on both stool and rectal swab specimens. The use of PCR tests on rectal swabs could reduce the time for the detection of CDI and improve the management of this infection. It should also provide a useful alternative for infection-control practitioners to better control the spread of C. difficile ., Competing Interests: The authors declare no conflict of interest.

Background: Measuring the ability of SARS-CoV-2 antibodies to neutralize live viruses remains an effective approach to quantify the level of protection of individuals. We assessed the neutralization activity against the ancestral SARS-CoV-2, Delta, Omicron BA.1, BA.2, BA.2.12.1, BA.4 and BA.5 strains, in 280 vaccinated restaurant/bar, grocery and hardware store workers in Québec, Canada., Methods: Participants were recruited during the emergence of Omicron BA.1 variant. The neutralizing activity of participant sera was assessed by microneutralization assay., Results: Serum neutralizing antibody (NtAb) titers of all participants against the ancestral SARS-CoV-2 strain were comparable with those against Delta variant (ranges of titers 10-2032 and 10-2560, respectively), however, their response was significantly reduced against Omicron BA.1, BA2, BA.2.12.1, BA.4 and BA.5 (10-1016, 10-1016, 10-320, 10-80 and 10-254, respectively). Individuals who received 2 doses of vaccine had significantly reduced NtAb titers against all SARS-CoV-2 strains compared to those infected and then vaccinated (≥1 dose), vaccinated (≥2 doses) and then infected, or those who received 3 doses of vaccine. Participants vaccinated with 2 or 3 doses of vaccine and then infected had the highest NtAb titers against all SARS-CoV-2 strains tested., Conclusion: We assessed for the first time the NtAb response in food and retail workers. We found that vaccination prior to the emergence of Omicron BA.1 was associated with higher neutralizing activity against pre-Omicron variants, suggesting the importance of updating vaccines to increase antibody response against new SARS-CoV-2 variants. Vaccination followed by infection was associated with higher neutralizing activity against all SARS-CoV-2 strains tested., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

Introduction: Some studies have found hot temperatures to be associated with exacerbations of schizophrenia, namely psychoses. As climate changes faster in Northern countries, our understanding of the association between temperature and hospital admissions (HA) for psychosis needs to be deepened., Objectives: 1) Among adults diagnosed with schizophrenia, measure the relationship between mean temperatures and HAs for psychosis during summer. 2) Determine the influence of individual and ecological characteristics on this relationship., Methods: A cohort of adults diagnosed with schizophrenia (n = 30,649) was assembled using Quebec's Integrated Chronic Disease Surveillance System (QICDSS). The follow-up spanned summers from 2001 to 2019, using hospital data from the QICDSS and meteorological data from the National Aeronautics and Space Administration's (NASA) Daymet database. In four geographic regions of the province of Quebec, a conditional logistic regression was used for the case-crossover analysis of the relationship between mean temperatures (at lags up to 6 days) and HAs for psychosis using a distributed lag non-linear model (DLNM). The analyses were adjusted for relative humidity, stratified according to individual (age, sex, and comorbidities) and ecological (material and social deprivation index and exposure to green space) factors, and then pooled through a meta-regression., Results: The statistical analyses revealed a statistically significant increase in HAs three days (lag 3) after elevated mean temperatures corresponding to the 90th percentile relative to a minimum morbidity temperature (MMT) (OR 1.040; 95% CI 1.008-1.074), while the cumulative effect over six days was not statistically significant (OR 1.052; 95% IC 0.993-1.114). Stratified analyses revealed non statistically significant gradients of increasing HAs relative to increasing material deprivation and decreasing green space levels., Conclusions: The statistical analyses conducted in this project showed the pattern of admissions for psychosis after hot days. This finding could be useful to better plan health services in a rapidly changing climate., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic inflammation persists in some people living with human immunodeficiency virus (HIV) during antiretroviral therapy and is associated with premature aging. The glycoprotein 120 (gp120) subunit of HIV-1 envelope sheds and can be detected in plasma, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasma soluble gp120 (sgp120) and a family of gp120-specific anti-cluster A antibodies, linked to CD4 depletion in vitro, contribute to chronic inflammation, immune dysfunction, and subclinical cardiovascular disease in participants of the Canadian HIV and Aging Cohort Study with undetectable viremia., Methods: Cross-sectional assessment of sgp120 and anti-cluster A antibodies was performed in 386 individuals from the cohort. Their association with proinflammatory cytokines and subclinical coronary artery disease was assessed using linear regression models., Results: High levels of sgp120 and anti-cluster A antibodies were inversely correlated with CD4+ T cell count and CD4/CD8 ratio. The presence of sgp120 was associated with increased levels of interleukin 6. In participants with detectable atherosclerotic plaque and detectable sgp120, anti-cluster A antibodies and their combination with sgp120 levels correlated positively with the total volume of atherosclerotic plaques., Conclusions: This study showed that sgp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of people living with HIV, contributing to the development of premature comorbid conditions., Competing Interests: Potential conflicts of interest. W. M., C. T., M. P., and A. F. received funding from ViiV Healthcare. A. C. is a full-time employee of ViiV Healthcare. All other authors report no potential 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.)

Objectives: Our objective was to report the baseline characteristics of participants in the Canadian HIV and Aging Cohort Study (CHACS) and present amendments to the initial protocol., Methods: CHACS is a multi-centred prospective cohort study that was initially set from 2011 to 2016 and will now continue recruitment until 2024. Four additional years of follow-up have been added, and additional outcomes and covariates will be prospectively collected. Frailty will be assessed using a modified version of the Fried's frailty phenotype. The four interrelated aspects of gender-gender roles, gender identity, gender relationships, and institutionalized gender-will be measured using the GENESIS-PRAXY questionnaire. Diet will be assessed using a validated, web-based, self-administered food frequency questionnaire., Results: A total of 1049 participants (77% people living with HIV) were recruited between September 2011 and September 2019. Median age at baseline was 54 years (interquartile range 50-61). Most participants were male (84%) and white (83%). Compared with participants without HIV, those with HIV were more likely to be male; to report lower education levels and incomes; to be more sedentary; to use tobacco, recreational, and prescription drugs; to report a personal history of cardiovascular diseases; and to be frail., Conclusions: The new assessments added to the CHACS protocol will allow for an even more detailed portrait of the pathways leading to accentuated aging for people living with HIV. Participants in the CHACS cohort display important differences in socio-economic and cardiovascular risk factors according to HIV serostatus. These imbalances must be taken into account for all further inferential analyses., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

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.)

Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretroviral therapy (ART). Our goal was to study the impact of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on bone mineral density (BMD) in peri- and early postmenopausal women living with HIV. This is a randomized international multicenter study of an early versus delayed (48-week) switch. BMD was measured by dual energy X-ray absorptiometry scan. Thirty-four women were enrolled: 19 in the immediate and 15 in the delayed switch arm from September 2017 to April 2019; 30 completed the 96-week protocol. The study closed for futility during the COVID-19 pandemic. The median (intraquartile range [IQR]) age was 51 years (47, 53), with a median (IQR) of 16.5 years (14, 23) since HIV diagnosis, median (IQR) 14 years (11, 20) of ART, and mean 8.6 years TDF. At enrollment, TDF was used in combination with a boosted protease inhibitor ( n  = 7), a non-nucleoside reverse transcriptase inhibitor ( n  = 13), an integrase inhibitor ( n  = 11), or more than one ART class ( n  = 3). The median (95% confidence interval [CI]) percentage change in BMD at the lumbar spine from 0 to 48 weeks in the immediate switch group was 1.97% (-1.15 to 5.49) compared with a median (95% CI) decrease of 2.32% (-5.11 to 0.19) in the delayed arm. The median (95% CI) percentage change in BMD from 0 to 96 weeks was 2.33% (0-4.51) in the immediate arm compared with 0.70% (-3.19 to 2.47) in the delayed arm. We demonstrated a trend to increased BMD at the lumbar spine after a switch from TDF to TAF in peri- and early postmenopausal women living with HIV. Clinical Trials.gov: NCT02815566.

COVID-19 represents a multi-system infectious disease with broad-spectrum manifestations, including changes in host metabolic processes connected to the disease pathogenesis. Understanding biochemical dysregulation patterns as a consequence of COVID-19 illness promises to be crucial for tracking disease course and clinical outcomes. Surface-enhanced Raman scattering (SERS) has attracted considerable interest in biomedical diagnostics for the sensitive detection of intrinsic profiles of unique fingerprints of serum biomolecules indicative of SARS-CoV-2 infection in a label-free format. Here, we applied label-free SERS and chemometrics for rapid interrogation of temporal metabolic dynamics in longitudinal sera of mildly infected non-hospitalized patients ( n = 22), at 4 and 16 weeks post PCR-positive diagnosis, and compared them with negative controls ( n = 8). SERS spectral markers revealed distinct metabolic profiles in patient sera that significantly deviated from the healthy metabolic state at the two sampling time intervals. Multivariate and univariate analyses of the spectral data identified abundance dynamics in amino acids, lipids, and protein vibrations as the key spectral features underlying the metabolic differences detected in convalescent samples and perhaps associated with patient recovery progression. A validation study performed using spontaneous Raman spectroscopy yielded spectral data results that corroborated SERS spectral findings and confirmed the detected disease-specific molecular phenotypes in clinical samples. Label-free SERS promises to be a valuable analytical technique for rapid screening of the metabolic phenotype induced by SARS-CoV-2 infection to allow appropriate healthcare intervention.

Introduction: Early in the COVID-19 pandemic, reagent availability was not uniform, and infrastructure had to be urgently adapted to undertake COVID-19 surveillance., Methods: Before the validation of centralized testing, two enzyme-linked immunosorbent assays (ELISA) were established independently at two decentralized sites using different reagents and instrumentation. We compared the results of these assays to assess the longitudinal humoral response of SARS-CoV-2-positive (i.e., PCR-confirmed), non-hospitalized individuals with mild to moderate symptoms, who had contracted SARSCoV-2 prior to the appearance of variants of concern in Québec, Canada., Results: The two assays exhibited a high degree of concordance to identify seropositive individuals, thus validating the robustness of the methods. The results also confirmed that serum immunoglobulins persist ≥ 6 months post-infection among non-hospitalized adults and that the antibodies elicited by infection cross-reacted with the antigens from P.1 (Gamma) and B.1.617.2 (Delta) variants of concern., Discussion: Together, these results demonstrate that immune surveillance assays can be rapidly and reliably established when centralized testing is not available or not yet validated, allowing for robust immune surveillance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Djaïleb, Lavallée, Parker, Cayer, Desautels, de Grandmont, Stuible, Gervais, Durocher, Trottier, Boudreau, Masson, Brouard and Pelletier.)

Background: Many people living with HIV struggle to consistently adhere to antiretroviral therapy, fail to achieve long-term virologic control and remain at risk for HIV-related disease progression, development of resistance and may transmit HIV infection to others., Objective: To determine if switching from current multi-tablet (curART) to single-tablet antiretroviral therapy (abacavir/lamivudine/dolutegravir; ABC/3TC/DTG), both combined with individualized adherence support, would improve HIV suppression in non-adherent vulnerable populations., Methods: TriiADD was an investigator-initiated randomized, multicentre, open label study. HIV+ adults with documented non-adherence on curART were randomized in a 1:1 ratio to immediately switch to ABC/3TC/DTG or to continue curART. Both arms received adherence support. The primary outcome was the proportion of participants in each arm with HIV RNA < 50 copies/mL 24 weeks after randomization., Results: In total, 50 people were screened and 27 randomized from 11 sites across Canada before the trial was stopped early due to slow recruitment. Participants were predominantly from ethnocultural communities, Indigenous people and/or had a history of injection drug use. The proportion achieving HIV RNA < 50 copies/mL at week 24 was 4/12 (33%) in the curART arm vs 7/13 (54%) in the ABC/3TC/DTG arm; median Bayesian risk difference, 5% (95% CrI, -17 to 28%) higher for those randomized to ABC/3TC/DTG. We encountered difficulties with recruitment of participants without prior drug resistance, retention despite intensive support, reliably measuring adherence and in overcoming entrenched adherence barriers., Conclusion: Results of our trial are consistent with a slight improvement in viral suppression in a vulnerable population when a single tablet regimen is combined with patient-level adherence support. Beyond treatment simplicity and tolerability, tailored interventions addressing stigma and social determinants of health are still needed. The numerous challenges we encountered illustrate how randomised trials may not be the best approach for assessing adherence interventions in vulnerable populations., Competing Interests: M.B.K. has received research support and consulting fees from ViiV Healthcare, AbbVie and Gilead. S.W. has received grants, consulting fees, lecture fees, nonfinancial support, and fees for the development of educational presentations from ViiV Health Care, GSK, Merck, Janssen, and Gilead Sciences. A.W. received consulting fees and honoraria from Merck, Gilead, ViiV Healthcare, and AbbVie. V.M.-L. has received research support from Gilead and Merck and consulting fees from AbbVie. N.P. has received honoraria from Gilead and ViiV Healthcare. B.C. is a board member, consultant, and has received grants and payment for lectures from AbbVie, Gilead, and Merck, and payment for educational presentations from AbbVie. J.A. serves on Advisory Boards for Gilead and ViiV and has performed contract research and other work for Gilead, ViiV and Merck. J.-G.B. has received consulting fees from Gilead Sciences, Merck, ViiV Healthcare, grants from Gilead Sciences, Merck, ViiV Healthcare, and payment for lectures from Gilead Sciences, Merck, ViiV Healthcare. C.F. has received grants from AbbVie, Gilead Sciences, Merck, and ViiV Healthcare. B.L. has received for investigator-initiated studies from ViiV Healthcare, Merck, and Gilead; consulting fees from ViiV Healthcare, Merck, and Gilead. He is the holder of a Canadian Institutes for Health Research, Strategy for Patient-Oriented Research Mentorship Chair in Innovative Clinical Trials for HIV Care. D.H.S.T. has received investigator-initiated research grants from AbbVie, Gilead Sciences inc. and ViiV Healthcare. D.H.S.T. is a Site Principal Investigator for clinical trials sponsored by Glaxo Smith Kline. Also, D.H.S.T. reports grants, personal fees from Canadian Institutes of Health Research, grants from Canada Research Chairs, grants from CIHR Canadian HIV Trials Network, during the conduct of the study. S.T. reports grants from GSK, outside the submitted work. The authors report no other conflicts of interest to declare., (© 2022 Klein et al.)

Background: Women living with HIV (WLWH) experience higher rates of human papillomavirus (HPV) infection and cervical cancer than women without HIV. Changes in the vaginal microbiome have been implicated in HPV-related disease processes such as persistence of high-risk HPV infection but this has not been well defined in a population living with HIV., Methods: Four hundred and 20 girls and WLWH, age ≥9, across 14 clinical sites in Canada were enrolled to receive three doses of quadrivalent HPV vaccine for assessment of vaccine immunogenicity. Blood, cervical cytology, and cervico-vaginal swabs were collected. Cervico-vaginal samples were tested for HPV DNA and underwent microbiota sequencing., Results: Principal component analysis (PCA) and hierarchical clustering generated community state types (CSTs). Relationships between taxa and CSTs with HPV infection were examined using mixed-effects logistic regressions, Poisson regressions, or generalized linear mixed-effects models, as appropriate. Three hundred and fifty-six cervico-vaginal microbiota samples from 172 women were sequenced. Human papillomavirus DNA was detected in 211 (59%) samples; 110 (31%) contained oncogenic HPV. Sixty-five samples (18%) were taken concurrently with incident oncogenic HPV infection and 56 (16%) were collected from women with concurrent persistent oncogenic HPV infection., Conclusions: No significant associations between taxa, CST, or microbial diversity and HPV-related outcomes were found. However, we observed weak associations between a dysbiotic microbiome and specific species, including Gardnerella , Porphyromonas , and Prevotella species, with incident HPV infection.

Rare earth elements (REEs) are considered critical elements for technology and their extraction through mining activities is expected to increase in the future. Due to their chemical similarities, they often co-occur in minerals and thus their ecotoxicity should be assessed as a group/family. However, the available ecotoxicological studies focused mainly on the evaluation of the potential toxicological impacts of individual REEs rather than their mixtures. The aim of this study was therefore to evaluate the toxicity of a representative mixture of five REEs (La, Ce, Pr, Nd and Sm) spanning environmentally relevant concentrations ranging from 0.05X (29 µg REEs L -1 ) to 5X (2926 µg REEs L -1 ) to the test organism, Hydra vulgaris, at the morphological, reproductive and regenerative levels. The data showed that lethality occurred at concentrations near (2.5 fold) to those inducing sublethal effects after chronic exposure of 7 days. The mixture affected reproduction and head regeneration and even lethality at concentrations even below those reported at environmental concentration (0.5X = 293 µg REEs L -1 ) in lakes. This suggests that REEs concentrations found in lakes near mining activities could disrupt regeneration and impair embryonic development. Our data also revealed that combining the 5 REEs results in an antagonistic effect, suggesting that those elements share the same receptor and that low molecular weight and high radius elements (approaching iron) were less toxic. Taken together, hydra could be used as a sensitive model organism for the assessment of aquatic ecotoxicological risks of REE mixtures but further analyses of biochemical and gene expressions should improve our understanding of the long-term effects of REEs mixtures., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

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.)

Objectives: To evaluate the spermicidal efficacy of non-hormonal vaginal gel in vitro and in a post-coital test, and to evaluate its contraceptive efficacy in Canadian women of childbearing age., Methods: We conducted single-centre trial to assess spermicidal and contraceptive efficacy of vaginal gel. Participants were healthy, sexually active women aged 18-49 years and their regular male sexual partners (30 couples). Measured outcomes included effect of vaginal gel on sperm motility in vitro, its effect on sperm in a post-coital test, and its effect on pregnancy prevention over 3 months., Results: For in vitro spermicidal effect, 98% and 67% of sperm were immotile in the presence of the gel with sodium lauryl sulfate (gel-SLS) and gel alone, respectively. For the post-coital test, 99% and 93% of sperm were immotile in the presence of gel-SLS and gel alone, respectively. In the second part of trial, a total of 410 instances of vaginal intercourse in 95 menstrual cycles were protected (during 3-month period of gel-SLS use before each sexual intercourse with probability of 24 conceptions prevented according to Wilcox's table). Four women became pregnant during the study period; 2 during unprotected vaginal intercourse around the time of ovulation, and 2 attributed to user failure., Conclusion: Based on our results, the vaginal gel demonstrated important spermicidal and contraceptive effect. A larger phase III contraceptive efficacy trial is warranted. The vaginal gel may represent a non-hormonal spermicide/contraceptive option for women., (Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

SARS-CoV-2 variants of concern (VOCs) have emerged worldwide, with implications on the spread of the pandemic. Characterizing the cross-reactivity of antibodies against these VOCs is necessary to understand the humoral response of non-hospitalized individuals previously infected with SARS-CoV-2, a population that remains understudied. Thirty-two SARS-CoV-2-positive (PCR-confirmed) and non-hospitalized Canadian adults were enrolled 14-21 days post-diagnosis in 2020, before the emergence of the B.1.351 (also known as Beta), B.1.617.2 (Delta) and P.1 (Gamma) VOCs. Sera were collected 4 and 16 weeks post-diagnosis. Antibody levels and pseudo-neutralization of the ectodomain of SARS-CoV-2 spike protein/human ACE-2 receptor interaction were analyzed with native, B.1.351, B.1.617.2 and P.1 variant spike proteins. Despite a lower response observed for the variant spike proteins, we report evidence of a sustained humoral response against native, B.1.351, B.1.617.2 and P.1 variant spike proteins among non-hospitalized Canadian adults. Furthermore, this response inhibited the interaction between the spike proteins from the different VOCs and ACE-2 receptor for ≥ 16 weeks post-diagnosis, except for individuals aged 18-49 years who showed no inhibition of the interaction between B.1.617.1 or B.1.617.2 spike and ACE-2. Interestingly, the affinity (K D ) measured between the spike proteins (native, B.1.351, B.1.617.2 and P.1) and antibodies elicited in sera of infected and vaccinated (BNT162b2 and ChAdOx1 nCoV-19) individuals was invariant. Relative to sera from vaccine-naïve (and previously infected) individuals, sera from vaccinated individuals had higher antibody levels (as measured with label-free SPR) and more efficiently inhibited the spike-ACE-2 interactions, even among individuals aged 18-49 years, showing the effectiveness of vaccination., (© 2021. The Author(s).)

Background: Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection., Methods: In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks., Results: The median age of the participants was 38 years, and 60% were women; 78% were White and 22% Black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-β receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer., Conclusions: In this phase 1, open-label clinical trial, a DNA vaccine elicited anti-ZIKV immune responses. Further studies are needed to better evaluate the safety and efficacy of the vaccine. (Funded by GeneOne Life Science and others; ZIKA-001 ClinicalTrials.gov number, NCT02809443.)., (Copyright © 2017 Massachusetts Medical Society.)

We report on the development of surface plasmon resonance (SPR) sensors and matching ELISAs for the detection of nucleocapsid and spike antibodies specific against the novel coronavirus 2019 (SARS-CoV-2) in human serum, plasma and dried blood spots (DBS). When exposed to SARS-CoV-2 or a vaccine against SARS-CoV-2, the immune system responds by expressing antibodies at levels that can be detected and monitored to identify the fraction of the population potentially immunized against SARS-CoV-2 and support efforts to deploy a vaccine strategically. A SPR sensor coated with a peptide monolayer and functionalized with various sources of SARS-CoV-2 recombinant proteins expressed in different cell lines detected human anti-SARS-CoV-2 IgG antibodies in clinical samples. Nucleocapsid expressed in different cell lines did not significantly change the sensitivity of the assays, whereas the use of a CHO cell line to express spike ectodomain led to excellent performance. This bioassay was performed on a portable SPR instrument capable of measuring 4 biological samples within 30 minutes of sample/sensor contact and the chip could be regenerated at least 9 times. Multi-site validation was then performed with in-house and commercial ELISA, which revealed excellent cross-correlations with Pearson's coefficients exceeding 0.85 in all cases, for measurements in DBS and plasma. This strategy paves the way to point-of-care and rapid testing for antibodies in the context of viral infection and vaccine efficacy monitoring.

Extracellular vesicles (EVs) and their contents (proteins, lipids, messenger RNA, microRNA, and DNA) are viewed as intercellular signals, cell-transforming agents, and shelters for viruses that allow both diagnostic and therapeutic interventions. EVs circulating in the blood of individuals infected with human immunodeficiency virus (HIV-1) may provide insights into pathogenesis, inflammation, and disease progression. However, distinguishing plasma membrane EVs from exosomes, exomeres, apoptotic bodies, virions, and contaminating proteins remains challenging. We aimed at comparing sucrose and iodixanol density and velocity gradients along with commercial kits as a means of separating EVs from HIV particles and contaminating protein like calprotectin; and thereby evaluating the suitability of current plasma EVs analysis techniques for identifying new biomarkers of HIV-1 immune activation. Multiple analysis have been performed on HIV-1 infected cell lines, plasma from HIV-1 patients, or plasma from HIV-negative individuals spiked with HIV-1. Commercial kits, the differential centrifugation and density or velocity gradients to precipitate and separate HIV, EVs, and proteins such as calprotectin, have been used. EVs, virions, and contaminating proteins were characterized using Western blot, ELISA, RT-PCR, hydrodynamic size measurement, and enzymatic assay. Conversely to iodixanol density or velocity gradient, protein and virions co-sedimented in the same fractions of the sucrose density gradient than AChE-positive EVs. Iodixanol velocity gradient provided the optimal separation of EVs from viruses and free proteins in culture supernatants and plasma samples from a person living with HIV (PLWH) or a control and revealed a new population of large EVs enriched in microRNA miR-155 and mitochondrial DNA. Although EVs and their contents provide helpful information about several key events in HIV-1 pathogenesis, their purification and extensive characterization by velocity gradient must be investigated thoroughly before further use as biomarkers. By revealing a new population of EVs enriched in miR-155 and mitochondrial DNA, this study paves a way to increase our understanding of HIV-1 pathogenesis.

Introduction and Hypothesis: To determine prevalence and quality of life impact of lower urinary tract symptoms (LUTS) in women living with HIV (WLWH)., Methods: Cross-sectional urinary questionnaires were included in a multicenter national prospective study of the HPV vaccine in WLWH. Demographic and clinical information was abstracted from the parent study. The Urinary Distress Inventory (UDI-6) and Urinary Impact Questionnaire (UIQ-7) were administered. Wilcoxon rank sum, two-sample chi-square or Fisher's exact tests were used as appropriate to compare women with UDI-6 score ≥ 25 to those with lower UDI-6 scores on demographic and HIV-related factors. Significant categorical variables were followed up with logistic regression to estimate odds ratios (OR)., Results: One hundred seventy-seven women completed urinary questionnaires (85.5% of cohort). Median age was 44.1 (37.2-50.6). Mean CD4 count was 621 (410-785), and 132 women (74.6%) were virologically suppressed. Median UDI-6 score was 4.2 (0-25). Fifty-one women (28.8%) had a UIQ-7 score > 0. Among those with a UDI-6 score of at least 25, median UIQ-7 was 9.5 (0-47.6). UDI-6 ≥ 25 was significantly associated with increasing age, higher BMI, Canada as country of origin, peri-/postmenopausal status (OR 3.37, 95% CI = 1.71 to 6.75) and being parous (OR 2.92, 95% CI = 1.27 to 7.59) (all p < 0.05). HIV-related factors were not associated with UDI-6 ≥ 25., Conclusions: LUTS were common, but we did not demonstrate a negative impact on quality of life in this sample of WLWH. Large comparative studies are needed to determine whether HIV is a risk factor for bothersome LUTS in women.

Background: Extracellular vesicles (EVs) are intercellular messengers with epigenetic potential since they can shuttle microRNA (miRNA). EVs and miRNA play a role in human immunodeficiency virus (HIV) infection immunopathogenesis. Chronic immune activation and systemic inflammation during HIV infection despite effective antiretroviral therapy (ART) are associated with non-acquired immunodeficiency syndrome (AIDS) comorbidities in people living with HIV (PLWH). Analysis of plasma EVs and their miRNA content may be useful as immune activation or inflammatory biomarkers in PLWH receiving ART. In this study, we hypothesized that the number, size, and miRNA of large and small EVs could reflect immune activation associated with an elevated CD8 T-cell count or a low CD4/CD8 ratio in PLWH., Methods: Plasma EVs subtype purified from PLWH and uninfected controls were sized using dynamic light scattering and quantified using flow cytometry and acetylcholine esterase (AChE) activity. Expression of mature miRNAs miR-92, miR-155, miR-223 was measured by quantitative reverse-transcriptase polymerase chain reaction in EVs and leucocytes., Results: HIV infection induces increased production of small EVs in plasma. EV subtypes were differentially enriched in miR-92, miR-155, and miR-223. Positive correlations between CD8 T-cell count and large EVs abundance and small EVs AChE activity were observed. CD4/CD8 ratio was negatively correlated with small EV AChE activity, and miRNA-155 level per small EV was negatively correlated with CD8 T-cell count., Conclusions: These findings suggest that quantifying large or small EVs and profiling miRNA content per EV might provide new functional biomarkers of immune activation and inflammation., Competing Interests: The authors declare that no competing interests exist. The funders had no role in study design, data collection and analysis, decision to publish, or manuscript preparation., (Copyright © Pathogens and Immunity 2021.)

Objective: To describe prevalent and persistent oncogenic human papillomavirus (HPV) types detected in women living with HIV (WLWH) in Canada, including women with cervical dyskaryosis, and to determine predictors of type-specific HPV persistence., Methods: Women and girls living with HIV, recruited from 14 sites of HIV care across Canada, were included in a sub-analysis of a prospective vaccine immunogenicity cohort study (two HPV DNA results, at least one cervical cytology result pre-vaccination). Demographic and clinical data were collected alongside cervical samples for cytology and HPV DNA typing between November 25, 2008, and May 19, 2015., Results: Pre-vaccination, HPV16 and HPV52 were the most prevalent oncogenic HPV types. Of the 252 women and girls who met the eligibility criteria, 45% were infected with at least one oncogenic HPV type and one-third of participants had a persistent oncogenic infection. HPV16, 45, and 52 were the most frequently persistent types. Seventeen percent of women had persistent infections with oncogenic HPV types not within currently available vaccines (HPV35/39/51/56/59/68/82). Lower CD4 count significantly predicted HPV persistence (P=0.024). Cervical cytology results were normal for 82.9% of participants, atypical squamous cells of undetermined significance for 2.4%, low-grade squamous intraepithelial lesions for 11.5%, and high-grade squamous intraepithelial lesions for 2.8%., Conclusion: Unvaccinated WLWH were infected with a wide range of oncogenic HPV types. The findings highlighted the importance of optimal treatment of HIV and continued cervical cancer screening as key steps toward the global elimination of cervical cancer., (© 2020 International Federation of Gynecology and Obstetrics.)

Background: Asymptomatic patients colonized with Clostridioides difficile are at risk of developing C. difficile infection (CDI), but the factors associated with disease onset are poorly understood. Our aims were to identify predictors of hospital-onset CDI (HO-CDI) among colonized patients and to explore the potential benefits of primary prophylaxis to prevent CDI., Methods: We conducted a retrospective cohort study in a tertiary academic institution. Colonized patients were identified by detecting the tcdB gene by polymerase chain reaction on a rectal swab. Univariate and multivariate logistic regression analyses were used to identify predictors of HO-CDI., Results: There were 19 112 patients screened, from which 960 (5%) colonized patients were identified: 513 met the inclusion criteria. Overall, 39 (7.6%) developed a HO-CDI, with a 30-day attributable mortality of 15%. An increasing length of stay (adjusted odds ratio [aOR] per day, 1.03; P = .006), exposure to multiple classes of antibiotics (aOR per class, 1.45; P = .02), use of opioids (aOR, 2.78; P = .007), and cirrhosis (aOR 5.49; P = .008) were independently associated with increased risks of HO-CDI, whereas the use of laxatives was associated with a lower risk of CDI (aOR 0.36; P = .01). Among the antimicrobials, B-lactam with B-lactamase inhibitors (OR 3.65; P < .001), first-generation cephalosporins (OR 2.38; P = .03), and carbapenems (OR 2.44; P = .03) correlated with the greatest risk of HO-CDI. By contrast, patient age, the use of proton pump inhibitors, and the use of primary prophylaxis were not significant predictors of HO-CDI., Conclusions: This study identifies several factors that are associated with CDI among colonized patients. Whether modifying these variables could decrease the risk of CDI should be investigated., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

HPV vaccination schedules have changed as evidence has supported reduced dosing and extended intervals. Women living with HIV (WLWH) represent an important population with no data on alternative dosing. Girls and WLWH received quadrivalent HPV (qHPV) vaccine in a pan-Canadian study of immunogenicity and efficacy. Serology was performed at months 0/2/7/12/18/24. Medical and sexual history was collected throughout. Linear regression was used to determine if spacing of doses was associated with peak antibody titer. Multivariable analyses demonstrated significant relationships between peak antibody titer and time to blood draw post last vaccine dose, naivety to the relevant HPV type, and HIV viral load for all qHPV types. There was a significant relationship between peak HPV16/18 antibody titer and age. Taking age, time to serology, CD4 cell count, CD4 nadir, HIV viral load, and HPV naivety into account, spacing of the three qHPV vaccine doses did not significantly impact peak antibody titers., 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. Disclosure of Interests Ms. McClymont has no conflicts. Dr. Ogilvie is a co-investigator on an investigator-led trial funded by Hologic Inc and Roche. Dr. Albert has no conflicts. Dr. Johnston has no conflicts. Dr. Raboud is a co-investigator on three projects outside the submitted work, with in-kind contributions or financial support from Merck and Gilead Sciences. Dr. Walmsley has received grants, personal fees and non-financial support from Merck Canada Inc., ViiV Healthcare, Gilead, AbbVie, Janssen and Bristol Meyers Squibb for participation on advisory boards, presentations, meetings, studies, workshops and symposia for each, outside the submitted work. Ms. Lipsky has no conflicts. Dr. Loutfy has received grant and honoraria funding from Merck Canada Inc., ViiV Healthcare, and Gilead, unrelated to the submitted work. Dr. Trottier has received grants from ViiV Healthcare, Gilead, GlaxoSmithKline, and Merck, outside the submitted work. Dr. Smaill received grant and honoraria funding from Merck Canada Inc., ViiV Healthcare, and Gilead, unrelated to the submitted work. Dr. Yudin has no conflicts. Dr. Klein has received funding for investigator-initiated research from ViiV and Merck, unrelated to this work, and honoraria for participation in advisory boards from Merck, ViiV, and BMS. Dr. Harris has received grants, paid to the institution, from the Canadian Institutes of Health Research (CIHR) and honoraria for consultancy and/or speaking engagements from Gilead Sciences Canada Inc., Merck Canada Inc., and ViiV Healthcare, outside the submitted work. Dr. Wobeser has received grants, paid to the institution, from CIHR and Merck Canada Inc., as well as honoraria for consultancy and/or speaking engagements from ViiV Healthcare, Gilead, AbbVie, and Janssen outside of the submitted work. Dr. Bitnun has no conflicts. Dr. Kakkar has no conflicts. Dr. Samson has no conflicts. Dr. Brophy has received honoraria for consultancy work from Merck Canada Inc., outside the submitted work. Dr. Karatzios has no conflicts. Dr. Money has received grants from GSK and Merck Canada Inc. for conducting sponsored vaccine trials. She also reports grants from Novartis and Sanofi for conducting sponsored vaccine trials in an unrelated area. She has received personal fees for symposium participation from Merck Canada Inc., outside the submitted work., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Human papillomavirus (HPV) vaccines have promising safety and immunogenicity data in women living with HIV (WLWH). However, it is critical to understand the residual burden of oncogenic HPV within WLWH to inform postvaccination cervical screening needs. We assessed rates of persistent infection with nonquadrivalent HPV (qHPV) oncogenic types in a cohort of qHPV-vaccinated WLWH., Setting: Multicentre, longitudinal cohort across Canada., Methods: WLWH were scheduled to receive 3 doses of qHPV vaccine. Participants provided health data and HPV DNA samples. Persistent cases of HPV were defined as new HPV in samples from ≥2 consecutive visits or as HPV present in the last sample. HPV31/33/35/39/45/51/52/56/58/59/68/82 were considered to have oncogenic potential. Median follow-up time was 4 years after initial vaccine dose., Results: A total of 284 participants were eligible for this analysis with 1205 person-years (PY) of follow-up (≥1 dose of vaccine, ≥1 HPV DNA result after vaccination). The highest incidence of persistent infection was with HPV51 (1.38/100 PY), followed by HPV52 (1.18/100 PY), and HPV39 (1.06/100 PY). The incidence of persistent infection with pooled HPV types added in the nonavalent vaccine (HPV31/33/45/52/58) was lower than the incidence of persistent oncogenic HPV types not contained within available vaccines (HPV35/39/51/56/59/68) (2.4/100 PY versus 3.6/100 PY, respectively)., Conclusions: qHPV-vaccinated WLWH continue to face a burden of persistent oncogenic HPV infection. Although the nonavalent vaccine could alleviate some of this burden, 2 of the top 3 persistent oncogenic HPVs in this cohort are not contained within any available vaccine. This highlights the need for ongoing cervical screening in HPV-vaccinated WLWH.

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 . 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: Human IL-32 is a polyfunctional cytokine that was initially reported to inhibit HIV-1 infection. However, recent data suggest that IL-32 may enhance HIV-1 replication by activating the HIV-1 primary targets, CD4 T-cells. Indeed, IL-32 is expressed in multiple isoforms, some of which are proinflammatory, whereas others are anti-inflammatory., Setting and Methods: Here, we aimed to determine the relative expression of IL-32 isoforms and to test their inflammatory nature and potential to induce HIV-1 production in latently infected cells from virologically suppressed HIV-infected individuals. IL-32 and other cytokines were quantified from plasma and supernatant of CD4 T-cells by ELISA. Transcripts of IL-32 isoforms were quantified by qRT-PCR in peripheral blood mononuclear cells. The impact of recombinant human IL-32 isoforms on HIV-1 transcription was assessed in CD4 T-cells from HIV-1cART individuals by qRT-PCR., Results: All IL-32 isoforms were significantly upregulated in HIV-1cART compared to HIV individuals with IL-32β representing the dominantly expressed isoform, mainly in T-cells and NK-cells. At the functional level, although IL-32γ induced typical proinflammatory cytokines (IL-6 and IFN-γ) in TCR-activated CD4 T-cells, IL-32α showed an anti-inflammatory profile by inducing IL-10 but not IL-6 or IFN-γ. However, IL-32β showed a dual phenotype by inducing both pro- and anti-inflammatory cytokines. Interestingly, consistent with its highly pro-inflammatory nature, IL-32γ, but not IL-32α or IL-32β, induced HIV-1 production in latently infected CD4 T-cells isolated from combined antiretroviral therapy-treated individuals., Conclusions: Our data report on the differential expression of IL-32 isoforms and highlight the potential role of IL-32, particularly the γ isoform, in fueling persistent inflammation and transcription of viral reservoir in HIV-1 infection.

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.)

Background: The 13-valent pneumococcal conjugate vaccine (PCV13) was recently shown to be effective against PCV13-type invasive pneumococcal disease (IPD) and pneumococcal community acquired pneumonia (CAP Spn ) in healthy adults aged ≥65 years, prompting many countries to re-assess adult immunization. In Canada, the potential benefits of adult PCV13 immunization were unclear given anticipated herd immunity from PCV13 childhood immunization introduced since 2010. This study describes the serotype distribution and clinical outcomes of Canadian adults aged ≥16 years, who were hospitalized with CAP Spn and IPD from 2010 to 2015., Methods: Active surveillance for CAP and IPD was performed in adult hospitals across five Canadian provinces. IPD was identified when Streptococcus pneumoniae was isolated from sterile sites. Bacteremic and non-bacteremic CAP Spn were identified using blood culture, and sputum culture or PCV13-specific urine antigen detection (UAD PCV13 ), respectively. Serotype was assigned using Quellung reaction, PCR, or UAD PCV13 ., Results: Of 6687 CAP cases where a test was performed, S. pneumoniae positivity decreased from 15.9% in 2011 to 8.8% in 2014, but increased to 12.9% in 2015. CAP Spn attributed to PCV13 serotypes followed a similar trend, dropping from 8.3% in 2010 to 4.6% in 2014, but increasing to 6.3% in 2015. The decline was primarily attributed to serotypes 7F and 19A, and the proportional increase to serotype 3. Similar trends were noted for bacteremic and non-bacteremic CAP Spn . Serious outcomes such as 30-day mortality, intensive care unit admission, and requirement for mechanical ventilation were prominent in CAP Spn and IPD cases, but remained unchanged over the study years., Conclusion: Herd immunity afforded primarily by serotypes 7F and 19A appears to be partly masked by a concomitant proportional increase of serotype 3. Despite evidence of herd immunity, these PCV13 serotypes remain persistent in Canadian adults hospitalized with CAP Spn , and represent between 5 and 10% of all CAP in this patient population., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Human papillomavirus (HPV) vaccination is safe and efficacious in women without human immunodeficiency virus (HIV). Although good immunogenicity has been observed in women living with HIV (WLWH), efficacy data in this population are needed., Methods: We enrolled 420 females aged ≥9 years (range, 9-65) living with HIV. Participants were to receive 3 doses of qHPV vaccine (0/2/6 months). The main endpoint was vaccine failure (ie, incident persistent qHPV infection, cervical intraepithelial neoplasia of grade 2 or higher [CIN2+], or genital warts). We compared these rates to published rates in vaccinated and unvaccinated women without HIV as well as unvaccinated WLWH., Results: Among 279 eligible women, median follow-up was 2 years. In the intention-to-treat population, the incidence rate (IR) of persistent qHPV (HPV6/11/16/18) was 2.3 per 100 person-years (/100PY) (95% confidence interval [CI], 1.1-4.1), and IR of genital warts was 2.3/100PY (95% CI, 1.2-4.1). In the per-protocol efficacy population, IR of persistent qHPV was 1.0/100PY (95% CI, 0.3-2.6) and of genital warts was 1.0/100PY (95% CI, 0.3-2.5). No cases of CIN2+ occurred. Reported rates of qHPV-related infection and disease within vaccinated women without HIV, unvaccinated women without HIV, and vaccinated WLWH: 0.1 (95% CI, 0.02-0.03), 1.5 (95% CI, 1.1-2.0), and 1.2 (95% CI, 0.2-3.4) /100PY, respectively. The rate of persistent qHPV among vaccinated WLWH was lower than among unvaccinated WLWH (2.3 vs 6.0/100PY)., Conclusions: Vaccinated WLWH may be at higher risk for vaccine failure than vaccinated women without HIV. However, overall rates of vaccine failure were low, and rates of persistent qHPV were lower than in unvaccinated WLWH., (© 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.)

Background: The effectiveness of influenza vaccination in reducing influenza-related hospitalizations among patients with COPD is not well described, and influenza vaccination uptake remains suboptimal., Methods: Data were analyzed from a national, prospective, multicenter cohort study including patients with COPD, hospitalized with any acute respiratory illness or exacerbation between 2011 and 2015. All patients underwent nasopharyngeal swab screening with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization. We identified influenza-positive cases and negative control subjects and used multivariable logistic regression with a standard test-negative design to estimate the vaccine effectiveness for preventing influenza-related hospitalizations., Results: Among 4,755 hospitalized patients with COPD, 4,198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis showed a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals. Influenza-positive patients (n = 1,833 [38.5%]) experienced higher crude mortality (9.7% vs 7.9%; P = .047) and critical illness (17.2% vs 12.1%; P < .001) compared with influenza-negative patients. Risk factors for mortality in influenza-positive patients included age > 75 years (OR, 3.7 [95% CI, 0.4-30.3]), cardiac comorbidity (OR, 2.0 [95% CI, 1.3-3.2]), residence in long-term care (OR, 2.6 [95% CI, 1.5-4.5]), and home oxygen use (OR, 2.9 [95% CI, 1.6-5.1])., Conclusions: Influenza vaccination significantly reduced influenza-related hospitalization among patients with COPD. Initiatives to increase vaccination uptake and early use of antiviral agents among patients with COPD could reduce influenza-related hospitalization and critical illness and improve health-care costs in this vulnerable population., Trial Registry: ClinicalTrials.govNo.:NCT01517191; URL www.clinicaltrials.gov., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

During 4 Clostridium difficile infection outbreaks, unit-wide screening of 114 patients led to detection and isolation of 15 (13%) C. difficile asymptomatic carriers. Carriage prevalence varied between outbreaks, from 0% to 29% (P = .004). Isolating carriers was not associated with significantly shorter outbreak durations, compared with historical controls.

Over the last few years, several of the world's national park networks have implemented ecological integrity monitoring programs. These programs are based on a series of indicators to detect changes in ecosystem integrity. There are many scientific and logistical challenges in developing these programs due to limits in both our knowledge of ecosystems functioning and the resources for implementing such programs. Thus, the relatively quick and simple implementation of many monitoring programs has been to the detriment of their scientific validity. Few studies have focused on evaluating an entire monitoring program. This project presents an approach to evaluate the ecological and statistical relevance of ecosystem integrity indicators measured within a program with the goal of iterative optimization. The approach is based on three complementary elements: (1) spatial characterization of park ecosystems based on the classification of satellite imagery, (2) ecological validation of indicators based on ecosystem conceptual models and (3) statistical validation of indicators based on analyses of statistical power. This innovative approach allows a systematic, quantified, reproducible and generalizable review of the indicators of an ecological integrity monitoring program. It provides managers with an overview of the spatial representativeness of indicators, their ecological and statistical relevance according to different parameters such as the period monitored, the amount of change to be detected, and the degree of significance. Thus, the approach identifies monitoring gaps and offers various alternatives for improving sampling. The approach was developed and tested in the network of Quebec national parks, more specifically in the Frontenac, Jacques-Cartier and Bic national parks. The results clearly identify the strengths and weaknesses of the current program in place and possible improvements are proposed for these parks. This approach is a relevant tool for park networks, particularly for those that have limited resources for monitoring ecological integrity., Competing Interests: The authors have declared that no competing interests exist.

Introduction: A Glasgow Coma Scale (GCS) score of 3 on presentation in patients with traumatic brain injury (TBI) portends a poor prognosis. Consequently, there is often a tendency to treat these patients less aggressively because of low expectations for a good outcome., Methods and Results: We performed a retrospective review of patients with TBI and a GCS score of 3. Patients were divided into 2 groups based on Glasgow Outcome Scale (GOS): Group 1 (GOS=1-3) and Group 2 (GOS=4-5). A total of 62 patients were included. The overall mortality rate was 80.6%. At 6-month, 9 patients (14.5%) achieved a GOS 4-5. Compared to Group 2 (n=9), Group 1 (n=53) had higher average APACHE IV score (104±19 vs 89±27, p=0.04), more patients with bilateral fixed pupils (59% vs 22%, p=0.04), and higher ICP burden (50±34 vs 0±0, p=0.0001). Using the CRASH calculator, the estimated mortality at 14days was 66% compared to actual mortality of 81%; difference of 15%, (p=0.05), and the estimated GOS 1-3 was 85.5% compared to actual of 85.5%, (p=1.0)., Conclusions: 14.5% of patients with TBI and a GCS of 3 at presentation achieved a good outcome at 6months, and 6.9% of patients with GCS of 3 and bilateral fixed pupils on presentation to the ED achieved a good outcome at 6months., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The isolation of asymptomatic Clostridium difficile (CD) carriers may decrease the incidence of hospital-associated C. difficile infections (CDI), but its impact on isolation precaution needs is unknown., Methods: A time series analysis was conducted to investigate the impact of isolating CD carriers on the burden of isolation precautions from 2008 to 2016 in a Canadian hospital. To account for the changes in C. difficile infection control policies, the series was divided into 3 intervention periods: period 1 (2008-2011), isolation of patients with CDI until symptom resolution; period 2 (2011-2013), isolation of patients with CDI until discharge; and period 3 (2013-2016), isolation of patients with CDI and CD carriers until discharge. We compared the prevalence of isolation-days for C. difficile (ie, for either CDI or carriage) per 1000 patient-days between study periods. Changes in trend were analyzed by segmented regression analysis., Results: A total of 806357 patient-days and 20455 isolation-days were included. Isolation-day prevalence during periods 1, 2, and 3 were 12.9, 26.2, and 37.8 isolation-days per 1000 patient-days, respectively (P < .001 between periods). Isolating CD carriers was associated with an increase in isolation-days' prevalence compared with period 2 (rate ratio [RR], 1.66; P < .001) followed by a significant decrease in trend (RR per 4-week period, 0.97; P < .001). The downward trend was mainly due to decreasing isolation needs for patients with CDI (RR per 4-week period, 0.94; P < .001) rather than for carriage (RR per 4-week period, 0.996; P = .21)., Conclusions: Isolating CD carriers led to an initial increase in isolation needs that was partially compensated by a decrease in isolation needs for CDI.

Background: Ongoing assessment of influenza vaccine effectiveness (VE) is critical to inform public health policy. This study aimed to determine the VE of trivalent influenza vaccine (TIV) for preventing influenza-related hospitalizations and other serious outcomes over three consecutive influenza seasons., Methods: The Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) conducted active surveillance for influenza in adults ≥16 years (y) of age during the 2011/2012, 2012/2013 and 2013/2014 seasons in hospitals across Canada. A test-negative design was employed: cases were polymerase chain reaction (PCR)-positive for influenza; controls were PCR-negative for influenza and were matched to cases by date, admission site, and age (≥65 y or <65 y). All cases and controls had demographic and clinical characteristics (including influenza immunization status) obtained from the medical record. VE was estimated as 1-OR (odds ratio) in vaccinated vs. unvaccinated patients × 100%. The primary outcome was VE of TIV for preventing laboratory-confirmed influenza-related hospitalization; secondary outcomes included VE of TIV for preventing influenza-related intensive care unit (ICU) admission/mechanical ventilation, and influenza-related death., Results: Overall, 3394 cases and 4560 controls were enrolled; 2078 (61.2%) cases and 2939 (64.5%) controls were ≥65 y. Overall matched, adjusted VE was 41.7% (95% Confidence Interval (CI): 34.4-48.3%); corresponding VE in adults ≥65 y was 39.3% (95% CI: 29.4-47.8%) and 48.0% (95% CI: 37.5-56.7%) in adults <65 y, respectively. VE for preventing influenza-related ICU admission/mechanical ventilation in all ages was 54.1% (95% CI: 39.8-65.0%); in adults ≥65 y, VE for preventing influenza-related death was 74.5% (95% CI: 44.0-88.4%)., Conclusions: While effectiveness of TIV to prevent serious outcomes varies year to year, we demonstrate a statistically significant and clinically important TIV VE for preventing hospitalization and other serious outcomes over three seasons. Public health messaging should highlight the overall benefit of influenza vaccines over time while acknowledging year to year variability. ClinicalTrials.gov Identifier: NCT01517191., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Limited resources warrant investigating models for predicting which stroke tissue-type plasminogen activator (tPA) patients benefit from admission to neurologic intensive care unit (neuroICU)., Methods: This model classifies patients who on day 1 of their ICU admission are predicted to receive one or more of 30 subsequent active life supporting treatments. Two groups of patients were compared: low risk monitor (LRM) (patients who did not receive active treatment (AT) on the first day and whose risk of ever receiving active treatment was ≤ 10%) and AT (patients who received at least one treatment on any day of their ICU admission)., Results: Compared to LRM group (21 patients), AT group (59 patients) had similar age (75 ± 13 vs. 72 ± 17, P = 0.4), similar gender (male: 56% vs. 52%, P = 0.8), similar National Institutes of Health stroke scale (NIHSS, 16 ± 9 vs. 14 ± 8, P = 0.4), and higher Acute Physiologic and Chronic Health Evaluation (APACHE) III scores (62 ± 26 vs. 41 ± 15, P = 0.0008). Compared to LRM group, AT group had longer ICU length of stay (4.5 ± 4.4 vs. 2.5 ± 1.3, P = 0.04), higher ICU mortality (22% vs. 4.7% (one patient DNR/hospice); OR: 5.6; 95% CI: 0.7 - 46.0; P = 0.1), and higher hospital mortality (36% vs. 4.7%; OR: 11; 95% CI: 1.4 - 88.0; P = 0.02)., Conclusion: The outcome of LRM patients with stroke post-tPA suggests that they may not require admission to a formal neuroICU, improving resource use and reducing costs.

Background: Consideration of cost determinants is crucial to inform delivery of public vaccination programs., Objectives: To estimate the average total cost of laboratory-confirmed influenza requiring hospitalization in Canadians prior to, during, and 30 days following discharge. To analyze effects of patient/disease characteristics, treatment, and regional differences in costs., Methods: Study utilized previously recorded clinical characteristics, resource use, and outcomes of laboratory-confirmed influenza patients admitted to hospitals in the Serious Outcomes Surveillance (SOS), Canadian Immunization Research Network (CIRN), from 2010/11 to 2012/13. Unit costs including hospital overheads were linked to inpatient/outpatient resource utilization before and after admissions., Results: Dataset included 2943 adult admissions to 17 SOS Network hospitals and 24 Toronto Invasive Bacterial Disease Network hospitals. Mean age was 69.5 years. Average hospital stay was 10.8 days (95% CI: 10.3, 11.3), general ward stays were 9.4 days (95% CI: 9.0, 9.8), and ICU stays were 9.8 days (95% CI: 8.6, 11.1) for the 14% of patients admitted to the ICU. Average cost per case was $14 612 CAD (95% CI: $13 852, $15 372) including $133 (95% CI: $116, $150) for medical care prior to admission, $14 031 (95% CI: $13 295, $14 768) during initial hospital stay, $447 (95% CI: $271, $624) post-discharge, including readmission within 30 days., Conclusion: The cost of laboratory-confirmed influenza was higher than previous estimates, driven mostly by length of stay and analyzing only laboratory-confirmed influenza cases. The true per-patient cost of influenza-related hospitalization has been underestimated, and prevention programs should be evaluated in this context., (© 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Associations between HIV-related stigma and reduced antiretroviral therapy (ART) adherence are widely established, yet the mechanisms accounting for this relationship are underexplored. There has been less attention to HIV-related stigma and its associations with ART initiation and current ART use. We examined pathways from HIV-related stigma to ART initiation, current ART use, and ART adherence among women living with HIV in Canada., Methods: We used baseline survey data from a national cohort of women living with HIV in Canada (n = 1425). Structural equation modeling using weighted least squares estimation methods was conducted to test the direct effects of HIV-related stigma dimensions (personalized, negative self-image, and public attitudes) on ART initiation, current ART use, and 90% ART adherence, and indirect effects through depression and HIV disclosure concerns, adjusting for sociodemographic factors., Results: In the final model, the direct paths from personalized stigma to ART initiation (β = -0.104, P < 0.05) and current ART use (β = -0.142, P < 0.01), and negative self-image to ART initiation (β = -0.113, P < 0.01) were significant, accounting for the mediation effects of depression and HIV disclosure concerns. Depression mediated the pathways from personalized stigma to ART adherence, and negative self-image to current ART use and ART adherence. Final model fit indices suggest that the model fit the data well [χ(25) = 90.251, P < 0.001; comparative fit index = 0.945; root-mean-square error of approximation = 0.044]., Conclusions: HIV-related stigma is associated with reduced likelihood of ART initiation and current ART use, and suboptimal ART adherence. To optimize the benefit of ART among women living with HIV, interventions should reduce HIV-related stigma and address depression.

Background: The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against severe outcomes. Here we report age- and strain-specific vaccine effectiveness (VE) in preventing severe outcomes during a season characterized by mixed outbreaks of four different influenza strains., Methods: This prospective, multicentre, test-negative case-control study evaluated the VE of trivalent influenza vaccine (TIV) in the prevention of laboratory-confirmed influenza-hospitalization in adults aged ≥16 years (all adults) and adults aged 16-64 years (younger adults). The SOS Network identified hospitalized patients with diagnoses potentially attributable to influenza during the 2011/12 influenza season. Swabs collected at admission were tested by reverse transcriptase polymerase chain reaction (RT PCR) or viral culture to discriminate influenza cases (positive) from controls (negative). VE was calculated as 1-odds ratio (OR) of vaccination in cases versus controls × 100., Results: Overall, in all adults, the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 41.8% (95% Confidence Interval [CI]: 26.0, 54.3), and 42.8% (95% CI: 23.8, 57.0), respectively. In younger adults (16-64 years), the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 35.8% (95% CI: 4.5, 56.8) and 33.2% (95% CI: -6.7, 58.2), respectively. In the all adults group, adjusted VE against influenza A/H1N1 was 72.5% (95% CI: 30.5, 89.1), against A/H3N2 was 86.1% (95% CI: 40.1, 96.8), against B/Victoria was 40.5% (95% CI: -28.9, 72.6), and against B/Yamagata was 32.3% (95% CI: -8.3, 57.7). The adjusted estimate of early season VE (from November 1 to March 11) was 54.4% (95% CI: 29.7-70.4), which was higher than late season (from March 11 to May 25) VE estimate (VE: 29.7%, 95% CI: -5.3, 53.1)., Conclusions: These results suggest that TIV was highly effective against A viruses and moderately effective against B viruses during a mild season characterised by co-circulation of four influenza strains in Canada. Findings underscore the need to provide VE assessment by subtype/lineage as well as the timing of vaccination (early season vs late season) to accurately evaluate vaccine performance and thus guide public health decision-making., Trial Registration: ClinicalTrials.gov Identifier: NCT01517191. Registration was retrospective and the date of registration was January 17, 2012.

Background: With potent antiretroviral drugs, HIV infection is becoming a chronic disease. Emergence of comorbidities, particularly cardiovascular disease (CVD) has become a leading concern for patients living with the infection. We hypothesized that the chronic and persistent inflammation and immune activation associated with HIV disease leads to accelerated aging, characterized by CVD. This will translate into higher incidence rates of CVD in HIV infected participants, when compared to HIV negative participants, after adjustment for traditional CVD risk factors. When characterized further using cardiovascular imaging, biomarkers, immunological and genetic profiles, CVD associated with HIV will show different characteristics compared to CVD in HIV-negative individuals., Methods/design: The Canadian HIV and Aging cohort is a prospective, controlled cohort study funded by the Canadian Institutes of Health Research. It will recruit patients living with HIV who are aged 40 years or older or have lived with HIV for 15 years or more. A control population, frequency matched for age, sex, and smoking status, will be recruited from the general population. Patients will attend study visits at baseline, year 1, 2, 5 and 8. At each study visit, data on complete medical and pharmaceutical history will be captured, along with anthropometric measures, a complete physical examination, routine blood tests and electrocardiogram. Consenting participants will also contribute blood samples to a research biobank. The primary outcome is incidence of a composite of: myocardial infarction, coronary revascularization, stroke, hospitalization for angina or congestive heart failure, revascularization or amputation for peripheral artery disease, or cardiovascular death. Preplanned secondary outcomes are all-cause mortality, incidence of the metabolic syndrome, incidence of type 2 diabetes, incidence of renal failure, incidence of abnormal bone mineral density and body fat distribution. Patients participating to the cohort will be eligible to be enrolled in four pre-planned sub-studies of cardiovascular imaging, glucose metabolism, immunological and genetic risk profile., Discussion: The Canadian HIV and Aging Cohort will provide insights on pathophysiological pathways leading to premature CVD for patients living with HIV.

Background: Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty., Methods: We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011-2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty., Results: Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%-73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%-73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased., Conclusions: Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased., Clinical Trials Registration: NCT01517191., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Pneumococcal community acquired pneumonia (CAP Spn ) and invasive pneumococcal disease (IPD) cause significant morbidity and mortality worldwide. Although childhood immunization programs have reduced the overall burden of pneumococcal disease, there is insufficient data in Canada to inform immunization policy in immunocompetent adults. This study aimed to describe clinical outcomes of pneumococcal disease in hospitalized Canadian adults, and determine the proportion of cases caused by vaccine-preventable serotypes., Methods: Active surveillance for CAP Spn and IPD in hospitalized adults was performed in hospitals across five Canadian provinces from December 2010 to 2013. CAP Spn were identified using sputum culture, blood culture, a commercial pan-pneumococcal urine antigen detection (UAD), or a serotype-specific UAD. The serotype distribution was characterized using Quellung reaction, and PCR-based serotyping on cultured isolates, or using a 13-valent pneumococcal conjugate vaccine (PCV13) serotype-specific UAD assay., Results and Conclusions: In total, 4769 all-cause CAP cases and 81 cases of IPD (non-CAP) were identified. Of the 4769 all-cause CAP cases, a laboratory test for S. pneumoniae was performed in 3851, identifying 14.3% as CAP Spn . Of CAP cases among whom all four diagnostic test were performed, S. pneumoniae was identified in 23.2% (144/621). CAP Spn cases increased with age and the disease burden of illness was evident in terms of requirement for mechanical ventilation, intensive care unit admission, and 30-day mortality. Of serotypeable CAP Spn or IPD results, predominance for serotypes 3, 7F, 19A, and 22F was observed. The proportion of hospitalized CAP cases caused by a PCV13-type S. pneumoniae ranged between 7.0% and 14.8% among cases with at least one test for S. pneumoniae performed or in whom all four diagnostic tests were performed, respectively. Overall, vaccine-preventable pneumococcal CAP and IPD were shown to be significant causes of morbidity and mortality in hospitalized Canadian adults in the three years following infant PCV13 immunization programs in Canada., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the immunogenicity and safety of the quadrivalent HPV (qHPV) vaccine in HIV-positive women over 24months., Design: Between November 2008 and December 2012, 372 women aged 15 and older were enrolled from 14 Canadian HIV outpatient clinics in an open label cohort study. The qHPV vaccine (0.5mL) was administered intramuscularly at months 0, 2 and 6. The primary study endpoint was seroconversion to any of the HPV types targeted by the qHPV vaccine. Antibody levels were measured at 0, 2, 7, 12, 18, and 24months. Adverse events were recorded throughout., Results: Of 372 participants enrolled, 310 (83%) received at least one dose of the qHPV vaccine and 277 (74%) received all three doses. Ninety-five percent (293/308) were seronegative for at least one vaccine type at baseline. The median age was 38years (IQR 32-45, range 15-66), 36% were white, 44% black and 13% were of Indigenous origin. Seventy-two percent of participants had a suppressed HIV viral load (VL<40c/ml) at baseline, with a median CD4 count of 510cells/mm(3) (376-695). Month 7 HPV type-specific seroconversion rates were 99.0%, 98.7%, 98.1% and 93.6% for HPV types 6, 11, 16 and 18 respectively in the per-protocol population. Participants with suppressed HIV VL at first vaccine had a 1.74-3.05fold higher peak antibody response compared to those without (p from 0.006 to <0.0001)., Conclusions: This study is the first to examine the qHPV vaccine in HIV-positive women out to 24months and the first to include HIV-positive women through to age 66. The qHPV vaccine was well tolerated, and highly immunogenic. As women with suppressed viral load had higher antibody responses, planning HPV vaccination to occur when persons are virologically suppressed would be optimal for maximizing immune response. Findings provide strong evidence that older HIV-positive women can still benefit from HPV vaccination., Clinical Trial Registration: http://www.isrctn.com/ISRCTN33674451., (Copyright © 2016. Published by Elsevier Ltd.)