Search

Introduction Nations thorughout the world are imposing mandatory quarantine on those entering the country. While such measures may be effective in reducing the importation of COVID-19, the mental health implications remain unclear. Objectives This study sought to assess mental well-being and factors associated with changes in mental health in individuals subject to mandatory quarantine following travel. Methods Travellers arriving at a large urban international airport completed online questionnaires on arrival and days 7 and 14 of mandated quarantine. Questionnaire items such as travel history, mental health, attitudes towards COVID-19, and protection behaviours were drawn from the World Health Organization Survey Tool for COVID-19. Results There was a clinically significant decline in mental health over the course of quarantine among the 10,965 eligible participants. Poor mental health was reported by 5.1% of participants on arrival and 26% on day 7 of quarantine. Factors associated with greater decline in mental health were younger age, female gender, negative views towards quarantine measures, and engaging in fewer COVID-19 prevention behaviours. Conclusions While the widespread use of quarantine may be effective in limiting the spread of COVID-19, the mental health implications are profound and have largely been ignored in public policy decision-making. Psychiatry has a role to play in contributing to the public policy debate to ensure that all aspects of health and well-being are reflected in decisions to isolate people from others. Disclosure No significant relationships.

Commercial assays measuring HPV E6 viral oncoproteins, E6/E7 mRNA or DNA were used to test neck lymph node fine needle aspirates (FNA) and oropharyngeal samples (saliva and oral swabs) from 59 Canadian patients with oropharyngeal squamous cell carcinomas (OPSCC). Overall agreements of p16 antigen staining of tumors to FNA tested for OncoE6™, Aptima HPV E6/E7 mRNA and cobas HPV DNA were 81.4% (k 0.53), 94.9% (k 0.83) and 91.1% (k 0.73) respectively. Using HPV presence in a subset of 25 tumors as the comparator, overall agreement was 64.0% (k 0.08) with OncoE6™, 88.0% (k 0.65) with Aptima HPV E6/E7 mRNA and 91.7% (k 0.70) with cobas HPV DNA. HPV testing of oropharyngeal samples yielded lower agreements with tumor markers; 23.7–24.0% (k 0.02), 55.9–68.0% (k 0.24–0.37) and 78.9–86.9% (k 0.49–0.58) in the 3 respective tests. HPV 16 was present in 93.7–100% of the samples tested and showed 100% genotype agreement between FNA and tumors. The high rates for HPV E6 oncoproteins and E6/E7 mRNA suggests most patients were experiencing transcriptionally active HPV-related OPSCC. Results from these commercial assays performed on FNA but not oropharyngeal samples showed moderate to very good agreements with p16 and HPV testing of tumors.

Research in the field of catalytic reduction of carbon dioxide to liquid fuels has grown rapidly in the past few decades. This is due to the increasing amount of carbon dioxide in the atmosphere and a steady climb in global fuel demand. This tutorial reviewwill present much of the significant work that has been done in the field of electrocatalytic and homogeneous reduction of carbon dioxide over the past three decades. It will then extend the discussion to the important conclusions from previous work and recommendations for future directions to develop a catalytic system that will convert carbon dioxide to liquid fuels with high efficiencies. [ABSTRACT FROM AUTHOR]

Background. Little is known about the impact of HIV infection on clinical presentation, complications, and morbid pericarditis-related outcomes of tuberculous pericarditis and its predictors. Objective. To assess the impact of HIV infection on presentation and outcomes in the multicountry Investigation of the Management of Pericarditis (IMPI) randomised controlled trial of immunotherapy in tuberculous pericarditis conducted in sub-Saharan Africa. Methods. We compared clinical features and outcomes of 1 370 adult patients treated for tuberculous pericarditis (939 and 431 HIVinfected and uninfected, respectively) enrolled in the IMPI trial. Cox proportional hazards models were used to determine independent predictors of outcomes of HIV-associated tuberculous pericarditis. Results. At presentation, HIV-infected (v. uninfected) patients were younger (median age 34.0 years v. 47.7 years), had lower body mass (mean weight 56 kg v. 60 kg), higher prevalence of tachycardia (58.5% v. 51.9%), hypotension (9.4% v. 3.9%), anaemia (65.9% v. 26.8%), and radiographic pulmonary infiltrates compatible with tuberculosis (35.4% v. 27.4%), but had lower rates of peripheral oedema (37.1% v. 48.3%). HIV-infected (v. uninfected) patients were less likely to develop constrictive pericarditis (4.1% v. 10.0% at 1 year, p

Nearly every industry faces the same question, whether they realize it yet or not: how do we reinvent our businesses to ensure resilience and prosperity today and into the future? The current linear economy is fraught with waste, inefficiencies, and toxic chemicals that cost businesses, consumers, and society. Since its inception more than 100 years ago, Steelcase has been on a path toward circularity. It began with operational excellence and product innovation. For the last decade, the company has been focusing on transformation through circular business models. This work involves product-service business models, new ways to engage with our customers, and a new lens to think about products. Green chemistry is a foundational component to delivering on this strategy and one we will explore in this article.

BACKGROUND: In 2007, Atlantic Canada experienced a large outbreak of mumps predominately in university students who had received a single dose of measles, mumps and rubella vaccine. The present study describes the performance characteristics of reverse transcriptase polymerase chain reaction (RT-PCR) on buccal and urine specimens and immunoglobulin M (IgM) serology in this partially immune population.

Background: To compare the effectiveness of four surveillance strategies for detecting SARS-CoV-2 within the homeless shelter population in Hamilton, ON and assess participant adherence over time for each surveillance method., Methods: This was an open-label, cluster-randomized controlled trial conducted in eleven homeless shelters in Hamilton, Ontario, from April 2020 to January 2021. All participants who consented to the study and participated in the surveillance were eligible for testing by self-swabbing. SARS-CoV-2 detection rate as the primary outcome, number of outbreaks, adherence, and overall acceptability were assessed. All participants, which included staff and residents, underwent daily symptom surveillance conducted by shelter staff and shelters were allocated to one of three asymptomatic surveillance arms (once weekly, self-collected oral swabs (OS); once-weekly self-collected oral-nasal swab (ONS); or once-weekly nurse collected nasopharyngeal swab (NPS) or a symptomatic only SARS-CoV-2 testing arm., Results: A total of 9747 SARS-CoV-2 tests were performed on 1570 participants. There were 4527 participants allocated to oral swab collection and 4935 participants allocated to oral-nasal swab collection. For nasopharyngeal swab collection, 285 participants were assigned before this arm was discontinued. The OS group identified 5 new cases (1.1 per 1000; 95% CI 0.4-2.3), while the ONS group identified 15 new cases (3.0 per 1000; 95% CI 1.9-4.7), resulting in a Risk Ratio (RR) of 2.76 (95% CI 1.00-7.58; p = 0.040). However, the mixed-effect model did not show a significantly higher positivity rate in the ONS compared to OS (OR 1.64; 95% CI 0.76-9.14; p = 0.129). Both ONS and OS were preferred over NPS, which did not detect any cases due to low adherence. Three outbreaks were identified during the study period within the shelters, two of the outbreaks had 2 positive cases each and the third outbreak had 3 positive cases., Conclusions: The two self-collection strategies were superior and showed the best adherence, with the ONS strategy shown to be superior or non-inferior in all measures. We are now studying the operationalization of a large-scale self-collected ONS surveillance strategy in a prospective cohort study of multiple homeless shelters. Funding was provided by the Hamilton Academic Hospital Organization (HAHSO) and Research St. Joseph's - Hamilton., Trial Registration: The trial was retrospectively registered with ClinicalTrials.gov on June 18, 2020, with the identifier NCT04438070., Competing Interests: Declarations. Ethics approval: The protocol for this trial was approved by the Hamilton Integrated Research Ethics Board (HiREB), and all shelters, residents, and staff provided verbal consent for involvement in the study. The trial was also registered on ClinicalTrials.gov, under identification number NCT04438070 (18/06/2020). This cluster-randomized multi-shelter trial was conducted according to the Consolidated Standards of Reporting Trials (CONSORT). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Haemophilus influenzae serotype a (Hia) has recently emerged as an important cause of invasive disease in the North American Arctic and Sub-Arctic regions, mainly affecting young Indigenous children. In this study, we addressed the question of whether the prevalence of Hia and all H. influenzae in the nasopharynx differed between paediatric populations from regions with high versus low incidence of invasive Hia disease. Nasopharyngeal specimens from children with acute respiratory tract infections (ARTI) collected for routine diagnostic detection of respiratory viruses were analysed with molecular-genetic methods to identify and serotype H. influenzae . In Nunavut, a region with a high incidence of invasive Hia disease, all H. influenzae and particularly Hia were found in the nasopharynx of 60.6% and 3.0% children. In Southern Ontario (Hamilton region), where Hia invasive disease is rare, the frequencies of all H. influenzae and Hia detection were 38.5% and 0.6%, respectively. In both cohorts, non-typeable H. influenzae was prevalent (57.0% and 37.9%, respectively). Considering that Hia is an important cause of severe invasive disease in Nunavut children, 3% prevalence of Hia among children with ARTI can reflect continuing circulation of the pathogen in the Northern communities that may result in invasive disease outbreaks.

Background: Essential workers, including those working in healthcare and education, are at higher risk of exposure to communicable diseases, including SARS-CoV-2. Reducing the rates of infection is important for their personal health and for the ongoing safe operation of essential services., Methods: Data from participants in two prospective cohort studies who tested positive for SARS-CoV-2 in 2020 through 2023 were used to determine whether vaccination against SARS-CoV-2 is associated with the severity of symptoms in working-age adults., Results: SARS-CoV-2-positive tests (N = 3757) were reported by 3093 participants (mean: 1.2 per person); 1229 (33%) illnesses did not interfere with regular activities, 1926 (51%) made participants too unwell for regular activities, and 602 (16%) required participant bed rest. Compared with vaccine receipt more than 12 months earlier, receipt within six months of an infection was associated with lower risk ratios for more severe illness (too unwell: 0.69 and bed rest: 0.67) compared with being able to conduct regular activities. More recent vaccination was also associated with lower odds reporting of systemic symptoms (fever, myalgia, arthralgia) and fewer solicited symptoms., Conclusion: Staying current with COVID-19 vaccinations should continue to be recommended since receiving a recent immunization lessened the severity of illness. Also, as symptoms of COVID-19 are now largely similar to other respiratory viruses, practitioners need to use this evidence to inform diagnostic testing and return-to-work policies.

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

The mechanisms by which respiratory viruses predispose to secondary bacterial infections remain poorly characterized. Using 2,409 nasopharyngeal swabs from 300 infants in Botswana, we performed a detailed analysis of factors that influence the dynamics of bacterial pathobiont colonization during infancy. We quantify the extent to which viruses increase the acquisition of Haemophilus influenzae , Moraxella catarrhalis , and Streptococcus pneumoniae . We provide evidence of cooperative interactions between these pathobionts while identifying host characteristics and environmental exposures that influence the odds of pathobiont colonization during early life. Using 16S rRNA gene sequencing, we demonstrate that respiratory viruses result in losses of putatively beneficial Corynebacterium and Streptococcus species that are associated with a lower odds of pathobiont acquisition. These findings provide novel insights into viral-bacterial relationships in the URT of direct relevance to respiratory infections and suggest that the URT bacterial microbiota is a potentially modifiable mechanism by which viruses promote bacterial respiratory infections., Competing Interests: Competing interests: MSK is a consultant for Merck & Co, Inc. and Invivyd. All other authors declare that they have no competing interests.

Breastfeeding and microbial colonization during infancy occur within a critical time window for development, and both are thought to influence the risk of respiratory illness. However, the mechanisms underlying the protective effects of breastfeeding and the regulation of microbial colonization are poorly understood. Here, we profiled the nasal and gut microbiomes, breastfeeding characteristics, and maternal milk composition of 2,227 children from the CHILD Cohort Study. We identified robust colonization patterns that, together with milk components, predict preschool asthma and mediate the protective effects of breastfeeding. We found that early cessation of breastfeeding (before 3 months) leads to the premature acquisition of microbial species and functions, including Ruminococcus gnavus and tryptophan biosynthesis, which were previously linked to immune modulation and asthma. Conversely, longer exclusive breastfeeding supports a paced microbial development, protecting against asthma. These findings underscore the importance of extended breastfeeding for respiratory health and highlight potential microbial targets for intervention., Competing Interests: Declaration of interests M.B.A. receives research funding from the Canadian and US governments, the Bill and Melinda Gates Foundation, and the Garfield Weston Foundation. She holds a Canada Research Chair in Early Nutrition and the Developmental Origins of Health and Disease and is a fellow of the CIFAR Humans and the Microbiome program. She has consulted for DSM Nutritional Products, serves on the scientific advisory board for TinyHealth, and has received speaking honoraria from Prolacta Biosciences. She has contributed without remuneration to online courses on breast milk and the infant microbiome produced by Microbiome Courses. L.B. receives research funding from the United States National Institutes of Health and the Bill and Melinda Gates Foundation. L.B. is the UC San Diego Chair of Collaborative Human Milk Research endowed by the Family Larsson-Rosenquist Foundation in Switzerland. V.B. is currently an employee of F. Hoffman-La Roche Ltd.; however, the published work was done prior to her employment and does not involve/promote any of Roche’s materials or point of view., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Although modern generative models achieve excellent quality in a variety of tasks, they often lack the essential ability to generate examples with requested properties, such as the age of the person in the photo or the weight of the generated molecule. To overcome these limitations we propose PluGeN (Plugin Generative Network), a simple yet effective generative technique that can be used as a plugin for pre-trained generative models. The idea behind our approach is to transform the entangled latent representation using a flow-based module into a multi-dimensional space where the values of each attribute are modeled as an independent one-dimensional distribution. In consequence, PluGeN can generate new samples with desired attributes as well as manipulate labeled attributes of existing examples. Due to the disentangling of the latent representation, we are even able to generate samples with rare or unseen combinations of attributes in the dataset, such as a young person with gray hair, men with make-up, or women with beards. In contrast to competitive approaches, PluGeN can be trained on partially labeled data. We combined PluGeN with GAN and VAE models and applied it to conditional generation and manipulation of images, chemical molecule modeling and 3D point clouds generation.

Background: People with HIV are at higher risk of infection-related cancers than the general population, which could be due, in part, to immune dysfunction. Our objective was to examine associations between 4 CD4 count measures as indicators of immune function and infection-related and infection-unrelated cancer risk., Setting: We conducted a cohort study of adults with HIV who were diagnosed with cancer in Ontario, Canada. Incident cancers were identified from January 1, 1997 to December 31, 2020., Methods: We estimated adjusted hazard ratios (aHR) for the associations between CD4 measures (baseline CD4, nadir CD4, time-updated CD4, time-updated CD4:CD8) and cancer incidence rates using competing risk analyses, adjusted for socio-demographic factors, history of hepatitis B or C infection, baseline viral load, smoking, and alcohol use., Results: Among 4771 people with HIV, contributing 59,111 person-years of observation, a total of 549 cancers were observed. Low baseline CD4 (<200 cells/µL) (aHR 2.08 [95% CI: 1.38 to 3.13], nadir (<200 cells/µL) (aHR 2.01 [95% CI: 1.49 to 2.71]), low time-updated CD4 (aHR 3.52 [95% CI: 2.36 to 5.24]) and time-updated CD4:CD8 ratio (<0.4) (aHR 2.02 [95% CI: 1.08 to 3.79]) were associated with an increased rate of infection-related cancer. No associations were observed for infection-unrelated cancers., Conclusions: Low CD4 counts and indices were associated with increased rates of infection-related cancers among people with HIV, irrespective of the CD4 measure used. Early diagnosis and linkage to care and high antiretroviral therapy uptake may lead to improved immune function and could add to cancer prevention strategies such as screening and vaccine uptake., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited., Methods: We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010 to 2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders., Results: Among 23 806 infants tested for influenza, 1783 (7.5%) were positive and 1708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI], 50%-74%). VE was similar by trimester of vaccination (first/second, 66% [95% CI, 40%-80%]; third, 63% [95% CI, 46%-74%]), infant age at testing (0 to <2 months, 63% [95% CI, 46%-75%]; 2 to <6 months, 64% [95% CI, 36%-79%]), and gestational age at birth (≥37 weeks, 64% [95% CI, 50%-75%]; < 37 weeks, 61% [95% CI, 4%-86%]). VE against influenza hospitalization was 67% (95% CI, 50%-78%)., Conclusions: Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available., Competing Interests: Potential conflicts of interest . During the conduct of this work, D. B. F. worked for the University of Ottawa and had academic appointments at the Children's Hospital of Eastern Ontario Research Institute and ICES; she is currently employed by Pfizer. K. W. is a cofounder and Chief Scientific Officer of CANImmunize, Inc; he served on the Independent Data Monitoring Committee for Medicago; and is a member of the Moderna Global Advisory Core Consultancy Group. 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.)

Background: In 2012, Botswana introduced 13-valent pneumococcal conjugate vaccine (PCV-13) to its childhood immunization program in a 3+0 schedule, achieving coverage rates of above 90% by 2014. In other settings, PCV introduction has been followed by an increase in carriage or disease caused by non-vaccine serotypes, including some serotypes with a high prevalence of antibiotic resistance., Methods: We characterized the serotype epidemiology and antibiotic resistance of pneumococcal isolates cultured from nasopharyngeal samples collected from infants (≤12 months) in southeastern Botswana between 2016 and 2019. Capsular serotyping was performed using the Quellung reaction. E-tests were used to determine minimum inhibitory concentrations for common antibiotics., Results: We cultured 264 pneumococcal isolates from samples collected from 150 infants. At the time of sample collection, 81% of infants had received at least one dose of PCV-13 and 53% had completed the three-dose series. PCV-13 serotypes accounted for 27% of isolates, with the most prevalent vaccine serotypes being 19F (n = 20, 8%), 19A (n = 16, 6%), and 6A (n = 10, 4%). The most frequently identified non-vaccine serotypes were 23B (n = 29, 11%), 21 (n = 12, 5%), and 16F (n = 11, 4%). Only three (1%) pneumococcal isolates were resistant to amoxicillin; however, we observed an increasing prevalence of penicillin resistance using the meningitis breakpoint (2016: 41%, 2019: 71%; Cochran-Armitage test for trend, p = 0.0003) and non-susceptibility to trimethoprim-sulfamethoxazole (2016: 55%, 2019: 79%; p = 0.04). Three (1%) isolates were multi-drug resistant., Conclusions: PCV-13 serotypes accounted for a substantial proportion of isolates colonizing infants in Botswana during a four-year period starting four years after vaccine introduction. A low prevalence of amoxicillin resistance supports its continued use as the first-line agent for non-meningeal pneumococcal infections. The observed increase in penicillin resistance at the meningitis breakpoint and the low prevalence of resistance to ceftriaxone supports use of third-generation cephalosporins for empirical treatment of suspected bacterial meningitis., Competing Interests: MSK is a consultant for Merck & Co, Inc. and Invivyd, and has research funding from Merck & Co., Inc. through Duke University. SIP has received honoraria from Pfizer, Inc., Merck Vaccines, GSK, and Sanofi for advisory board participation, data safety monitoring board membership, and consulting related to pneumococcal conjugate vaccines. SIP additionally receives research funding from Merck & Co., Inc. and Pfizer through Boston Medical Center. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors report no relevant conflicts of interest”., (Copyright: © 2024 Hurst et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

More than a decade after the Consolidated Standards of Reporting Trials group released a reporting items checklist for non-inferiority randomized controlled trials, the infectious diseases literature continues to underreport these items. Trialists, journals, and peer reviewers should redouble their efforts to ensure infectious diseases studies meet these minimum reporting standards., Competing Interests: Potential conflicts of interest . A. K. K. reports receipt of an honorarium from Gilead for a regional review lecture on the Conference on Retroviruses and Opportunistic Infections; M. S. reports grant funding unrelated to this publication from the Canadian Institutes of Health Research and Air Canada (COVID-19 in International Travelers Study: staff and reagent costs), and the Ontario Research Fund for COVID research (COVID Automation: equipment costs); and M. L. reports a contract with the WHO to help update antibiotics in the Essential Medicines List. 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. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aOR per 28 days  = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aOR per 28 days  = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Background: The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 virus, emerged in late 2019 and spready globally. Many effects of infection with this pathogen are still unknown, with both chronic and repeated COVID-19 infection producing novel pathologies., Case Presentation: An immunocompromised patient presented with chronic COVID-19 infection. The patient had history of Hodgkin's lymphoma, treated with chemotherapy and stem cell transplant. During the course of their treatment, eleven respiratory samples from the patient were analyzed by whole-genome sequencing followed by lineage identification. Whole-genome sequencing of the virus present in the patient over time revealed that the patient at various timepoints harboured three different lineages of the virus. The patient was initially infected with the B.1.1.176 lineage before coinfection with BA.1. When the patient was coinfected with both B.1.1.176 and BA.1, the viral populations were found in approximately equal proportions within the patient based on sequencing read abundance. Upon further sampling, the lineage present within the patient during the final two timepoints was found to be BA.2.9. The patient eventually developed respiratory failure and died., Conclusions: This case study shows an example of the changes that can happen within an immunocompromised patient who is infected with COVID-19 multiple times. Furthermore, this case demonstrates how simultaneous coinfection with two lineages of COVID-19 can lead to unclear lineage assignment by standard methods, which are resolved by further investigation. When analyzing chronic COVID-19 infection and reinfection cases, care must be taken to properly identify the lineages of the virus present., (© 2024. The Author(s).)

Background: People with HIV infection are at higher risk for certain cancers than the general population. We compared trends in infection-related and infection-unrelated cancers among people with and without HIV infection., Methods: We conducted a retrospective population-based matched cohort study of adults with and without HIV infection using linked health administrative databases in Ontario, Canada. Participants were matched on birth year, sex, census division (rurality), neighbourhood income quintile and region of birth. We followed participants from cohort entry until the earliest of date of cancer diagnosis, date of death, Nov. 1, 2020, or date of loss to follow-up. Incident cancers identified from Jan. 1, 1996, to Nov. 1, 2020, were categorized as infection-related or-unrelated. We examined calendar periods 1996-2003, 2004-2011 and 2012-2020, corresponding to the early combination antiretroviral therapy (cART), established cART and contemporary cART eras, respectively. We used competing risk analyses to examine trends in cumulative incidence by calendar period, age and sex, and cause-specific hazard ratios (HRs)., Results: We matched 20 304 people with HIV infection to 20 304 people without HIV infection. A total of 2437 cancers were diagnosed, 1534 (62.9%) among infected people and 903 (37.0%) among uninfected people. The risk of infection-related cancer by age 65 years for people with HIV infection decreased from 19.0% (95% confidence interval [CI] 15.6%-22.3%) in 1996-2011 to 10.0% (95% CI 7.9%-12.1%) in 2012-2020. Compared to uninfected people, those with HIV infection had similar HRs of infection-unrelated cancer but increased rates of infection-related cancer, particularly among younger age groups (25.1 [95% CI 13.2-47.4] v. 1.9 [95% CI 1.0-3.7] for age 18-39 yr v. ≥ 70 yr); these trends were consistent when examined by sex. Interpretation: We observed significantly higher rates of infection-related, but not infection-unrelated, cancer among people with HIV infection than among uninfected people. The elevated rate of infection-related cancer in 2012-2020 highlights the importance of early and sustained antiretroviral therapy along with cancer screening and prevention measures., Competing Interests: Competing interests: Marek Smieja reports funding from the Canadian Institutes of Health Research, Air Canada and the Greater Toronto Airports Authority. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year., Methods: We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 ARV regimens used for human immunodeficiency virus treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarize data; statistical tests were 2 sided, with significance defined as P < .05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded., Results: We included 160 articles reporting 171 trials. Of these articles, 101 (63.1%) did not justify the NI margin used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat and per-protocol analyses, while 118 (73.8%) described missing data handling. Ten of 171 trials (5.9%) reported potentially misleading results. Pharmaceutical industry-funded trials were more likely to be double-blinded (28.1% vs 10.3%; P = .03) and to describe missing data handling (78.5% vs 59.0%; P = .02). The overall risk of bias was low in 96 of 160 studies (60.0%)., Conclusions: ARV NI-RCTs should improve NI margin justification, reporting of intention-to-treat and per-protocol analyses, and missing data handling to increase CONSORT adherence., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Respiratory syncytial virus (RSV) contributes significantly to morbidity in children, placing substantial burdens on health systems, thus RSV vaccine development and program implementation are a public health priority. More data on burden are needed by policymakers to identify priority populations and formulate prevention strategies as vaccines are developed and licensed., Methods: Using health administrative data, we calculated incidence rates of RSV hospitalization in a population-based birth cohort of all children born over a six-year period (May 2009 to June 2015) in Ontario, Canada. Children were followed until their first RSV hospitalization, death, 5th birthday, or the end of the study period (June 2016). RSV hospitalizations were identified using a validated algorithm based on International Classification of Diseases, 10th Revision, and/or laboratory-confirmed outcomes. We calculated hospitalization rates by various characteristics of interest, including calendar month, age groups, sex, comorbidities, and gestational age., Results: The overall RSV hospitalization rate for children <5 years was 4.2 per 1000 person-years (PY) with a wide range across age groups (from 29.6 to 0.52 per 1000 PY in children aged 1 month and 36-59 months, respectively). Rates were higher in children born at a younger gestational age (23.2 per 1000 PY for those born at <28 weeks versus 3.9 per 1000 PY born at ≥37 weeks); this increased risk persisted as age increased. While the majority of children in our study had no comorbidities, rates were higher in children with comorbidities. For all age groups, rates were highest between December and March., Conclusions: Our results confirm the high burden of RSV hospitalization and highlight young infants are at additional risk, namely premature infants. These results can inform prevention efforts., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Background: Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk., Methods: Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010-2011 to 2018-2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status., Results: Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%-20%] and 17% [13%-21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10-1.21] and 1.15 [1.10-1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for β-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated β-blocker users., Conclusions: Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding., Competing Interests: Potential conflicts of interest. H. C., M. A. C., S. A. B., T. K., K. L. S., and J. C. K. report support from the Canadian Institutes of Health Research (CIHR; grant PJT 159516, paid to the institution). J. B. G. has received research grants from GSK and Hoffmann-LaRoche for antiviral resistance studies and from Pfizer to conduct microbiological surveillance of Streptococcus pneumoniae. J. B. G. also reports consulting fees from GIDEON Informatics, as a scientific editor, unrelated to the current work. A. J. M. reports research funds from GSK; grants or contracts from Sanofi, Merck, and Pfizer (paid to the institution); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Merck, Biogen, and Moderna; and participation on a data safety monitoring board or advisory board for Pfizer, GlaxoSmithKline, Moderna, Medicago, Janssen, AstraZeneca, Novavax, and Sanofi. D. C. R. reports participation on a data safety monitoring board or advisory board for GlaxoSmithKline (advisory board meeting on monoclonal antibodies for coronavirus disease 2019 [COVID-19]). M. S. reports grants or contracts from CIHR, Air Canada (staff and reagent costs for the COVID in International Travelers Study), the Ontario Research Fund (equipment costs for COVID-19 automation), and the Juravinski Research Fund (staff and equipment for COVID-19 diagnostic testing). G. Z. reports support from CIHR (paid to grant administered by J. C. K.) and grants from Genome Atlantic and PHAC. Roche and Abbott contribute unrestricted educational funding to the Eastern Health Regional Health Authority for employees, which include G. Z., to attend virtual meetings and, in specific restricted circumstances, travel to educational, technical, and research meetings. G. Z. is also the previous president of the National Molecular Users Group. 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.)

Isolating and characterizing emerging SARS-CoV-2 variants is key to understanding virus pathogenesis. In this study, we isolated samples of the SARS-CoV-2 R.1 lineage, categorized as a variant under monitoring by the World Health Organization, and evaluated their sensitivity to neutralizing antibodies and type I interferons. We used convalescent serum samples from persons in Canada infected either with ancestral virus (wave 1) or the B.1.1.7 (Alpha) variant of concern (wave 3) for testing neutralization sensitivity. The R.1 isolates were potently neutralized by both the wave 1 and wave 3 convalescent serum samples, unlike the B.1.351 (Beta) variant of concern. Of note, the R.1 variant was significantly more resistant to type I interferons (IFN-α/β) than was the ancestral isolate. Our study demonstrates that the R.1 variant retained sensitivity to neutralizing antibodies but evolved resistance to type I interferons. This critical driving force will influence the trajectory of the pandemic.

Over 2-years of follow-up, integrase strand transfer inhibitor (INSTI)-use was associated with weight gain among those on an INSTI <2 years at entry (+0.27 kg/m2/year; 95% confidence interval [CI], .22 to .33 vs +0.17 kg/m2/year; 95% CI, .12 to .23; P = .01), but not those on an entry INSTI >2 years., Competing Interests: Potential conflicts of interest. C. D. M. reports institutional research grants from Lilly and personal fees from ViiV Healthcare and Gilead Sciences for participation in advisory board meetings outside the submitted work. J. L. reports consulting fees from ViiV Healthcare and Gilead Sciences, Inc, as well as investigator-initiated research grant support from ViiV Healthcare related to this work. C. J. F. reports grant support through their institution from Gilead Sciences, ViiV Healthcare, GSK, Janssen, AbbVie, Merck, Amgen, and Cytodyn, outside the submitted work; personal fees from Theratechnologies and ViiV Healthcare for consulting and participation on an advisory board unrelated to Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE); and a role as chair on the data and safety monitoring board (DSMB) for the Intrepid Study, outside the submitted work. J. A. A. reports institutional research support for clinical trials from Atea, Emergent Biosolutions, Frontier Technologies, Gilead Sciences, GSK, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare; personal fees for participation on advisory boards from GSK/ViiV Healthcare and Merck; and participation on a DSMB from Kintor, all outside the submitted work. M. V. Z. reports grant support through their institution from NIH/NIAID and Gilead Sciences, Inc, relevant to the conduct of the study, as well as grants from NIH/NIAID and NIH/NHLBI, outside the submitted work; unpaid participation on a DSMB for NIH-funded studies; and support for meetings and/or travel from Conference on Retroviruses and Opportunistic Infections (CROI) and the International Workshop for HIV and Women from the conference organizing committee as an abstract reviewer and/or speaker. E. M. reports consulting fees and honoraria for lectures from Gilead Sciences, ViiV Healthcare, Janssen, and MSD; advisory board participation for ViiV Healthcare and MSD; and that their institution has received research grants from Gilead, Janssen, MSD, Theratechnologies, and ViiV Healthcare, unrelated to the submitted work. N. L. O. reports grants from NIH/NHLBI during the conduct of the study and consulting fees from Gilead Sciences unrelated to the submitted work. P. K. serves as a consultant and receives research funding from ViiV Healthcare, Merck, Theratechnologies, and Gilead and owns stock in Pfizer, Gilead, Merck, GSK, and Moderna. S. H. B. reports serving as a scientific advisor to Gilead Sciences including payment for expert testimony and research grants to their institution from Gilead Sciences, ViiV Healthcare, and Janssen unrelated to the submitted work. J. C. R. reports work supported by NIAID of the NIH. H. J. R. reports grants from NIH/NHLBI and Kowa Pharmaceuticals America, Inc, during the conduct of the study as well as grants from NIH/NIAID, NIH/NHLBI, NIH/National Institute of Diabetes and Digestive and Kidney Diseases, and NIH/National Institute on Aging outside the submitted work. S. K. G. reports grants from NIH, Kowa Pharmaceuticals America, Inc, Gilead Sciences, and ViiV Healthcare during the conduct of the study; personal consulting fees from Theratechnologies, ViiV Healthcare, and Marathon Asset Management outside the submitted work; and participation on the Marathon Asset Management Scientific Advisory Board. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To describe children hospitalized with community-acquired pneumonia complicated by effusion (cCAP)., Design: Retrospective cohort study., Setting: A Canadian children's hospital., Participants: Children without significant medical comorbidities aged < 18 years admitted from January 2015-December 2019 to either the Paediatric Medicine or Paediatric General Surgery services with any pneumonia discharge code who were documented to have an effusion/empyaema using ultrasound., Outcome Measures: Length of stay; admission to the paediatric intensive care unit; microbiologic diagnosis; antibiotic use., Results: There were 109 children without significant medical comorbidities hospitalized for confirmed cCAP during the study period. Their median length of stay was 9 days (Q1-Q3 6-11 days) and 35/109 (32%) were admitted to the paediatric intensive care unit. Most (89/109, 74%) underwent procedural drainage. Length of stay was not associated with effusion size but was associated with time to drainage (0.60 days longer stay per day delay in drainage, 95%CI 0.19-1.0 days). Microbiologic diagnosis was more often made via molecular testing of pleural fluids (43/59, 73%) than via blood culture (12/109, 11%); the main aetiologic pathogens were S. pneumoniae (40/109, 37%), S. pyogenes (15/109, 14%), and S. aureus (7/109, 6%). Discharge on a narrow spectrum antibiotic (i.e. amoxicillin) was much more common when the cCAP pathogen was identified as compared to when it was not (68% vs. 24%, p < 0.001)., Conclusions: Children with cCAP were commonly hospitalized for prolonged periods. Prompt procedural drainage was associated with shorter hospital stays. Pleural fluid testing often facilitated microbiologic diagnosis, which itself was associated with more appropriate antibiotic therapy., (© 2023. The Author(s).)

Background: Rhino-enteroviruses, particularly enterovirus strain D68 (EV-D68), have been associated with severe respiratory distress in children. The goal of this study was to compare the long-term outcomes of children with EV-D68 infection to that of children with other enterovirus / rhinovirus., Methods: Nasopharyngeal swabs from 174 children presenting with respiratory distress were tested by PCR for respiratory viruses. The primary outcome was diagnosis of a chronic respiratory condition within the follow-up period. Admission to intensive care, and length of stay were recorded. Odds ratios were determined using multinomial logistic regression., Results: During 5 years of follow-up, the crude odds of diagnosis with a chronic respiratory condition were significantly more likely in EV-D68 cases (OR: 1.95, 95% CI: 1.02, 3.82), but failed to remain significant after adjusting for a past history of asthma. Upon admission for a primary concern of asthma, length of stay both in hospital and intensive care were significantly longer in EV-D68 cases (OR: 2.10 [95% CI: 1.56, 2.82, p < 0.001]) and (OR: 5.18 [95% CI: 1.90, 6.28, p < 0.001]), respectively. After adjustment for a history of asthma, EV-D68 cases had significantly longer length of stay in hospital, admitted for 1.94 days for each day that controls were admitted (95% CI: 1.40, 2.68). In admissions to intensive care, EV-D68 cases spent 2.74 days for each day of admission in controls (95% CI: 1.62, 4.97, p < 0.001)., Conclusions: Ours is first study to assess prognostic respiratory outcomes of patients infected with EV-D68 in childhood. Our study finds that EV-D68 cases were significantly more likely be hospitalized for longer than other enterovirus/rhinovirus controls in subsequent admissions for respiratory distress. Need for intensive care was significantly longer in EV-D68 infections. Our next steps will be validation in a larger sample size., (© 2022 The Author(s).)