Comparing cefazolin/ metronidazole, piperacillin-tazobactam, or c efoxitin as surgical antibiotic prophylaxis in patients undergoing pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. OBJECTIVE: To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). METHODS: Consecutive adult patients at one institution who underwent PD from November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. RESULTS: Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. CONCLUSION: PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PD at our center.

WHO's essential medicines and AWaRe: recommendations on first- and second-choice antibiotics for empiric treatment of clinical infections.

The WHO Model List of Essential Medicines (EML) prioritizes medicines that have significant global public health value. The EML can also deliver important messages on appropriate medicine use. Since 2017, in response to the growing challenge of antimicrobial resistance, antibiotics on the EML were reviewed and categorized into three groups: Access, Watch and Reserve, leading to a new categorization called AWaRe. These categories were developed taking into account the impact of different antibiotics and classes on antimicrobial resistance, and the implications for their appropriate use. The 2023 AWaRe classification provides empiric guidance on 41 essential antibiotics for over 30 clinical infections targeting both the primary health care and hospital facility setting. A further 257 antibiotics not included on the EML have been allocated an AWaRe group for stewardship and monitoring purposes. This article describes the development of AWaRe focussing on the clinical evidence base that guided the selection of Access, Watch or Reserve antibiotics as first and second choices for each infection. The overarching objective was to offer a tool for optimising the quality of global antibiotic prescribing and reduce inappropriate use by encouraging the use of Access antibiotics (or no antibiotics) where appropriate. This clinical evidence evaluation and subsequent EML recommendations are the basis for the AWaRe antibiotic book and related smartphone applications. By providing guidance on antibiotic prioritization, AWaRe aims to facilitate the revision of national lists of essential medicines, update of national prescribing guidelines and surveillance of antibiotic use. Adherence to AWaRe would extend the effectiveness of current antibiotics while helping countries to expand access to these life-saving medicines for the benefit of current and future patients, health professionals, and the environment.

Measures of retention in HIV care: A protocol for a mixed methods study.

INTRODUCTION: Retention in HIV care is necessary to achieve adherence to antiretroviral therapy, viral load suppression, and optimal health outcomes. There is no standard definition for retention in HIV care, which compromises consistent and reliable reporting and comparison of retention across facilities, jurisdictions, and studies. OBJECTIVE: The objective of this study is to explore how stakeholders involved in HIV care define retention in HIV care and their preferences on measuring retention. METHODS: We will use an exploratory sequential mixed methods design involving HIV stakeholder groups such as people living with HIV, people involved in providing care for PLHIV, and people involved in decision-making about PLHIV. In the qualitative phase of the study, we will conduct 20-25 in-depth interviews to collect the perspectives of HIV stakeholders on using their preferred retention measures. The findings from the qualitative phase will inform the development of survey items for the quantitative phase. Survey participants (n = 385) will be invited to rate the importance of each approach to measuring retention on a seven-point Likert scale. We will merge the qualitative and quantitative findings phase findings to inform a consensus-building framework for a standard definition of retention in care. ETHICAL ISSUES AND DISSEMINATION: This study has received ethics approval from the Hamilton Integrated Research Ethics Board. The findings will be disseminated through peer-reviewed publications, conference presentations, and among stakeholder groups. LIMITATIONS: This study has limitations; we won't be able to arrive at a standard definition; a Delphi technique amongst the stakeholders will be utilized using the framework to reach a consensus globally accepted definition.

Extracorporeal membrane oxygenation for COVID-19-associated severe acute respiratory distress syndrome in Canada: Analysis of data from the Canadian Nosocomial Infection Surveillance Program.

Background: Extracorporeal membrane oxygenation (ECMO) for COVID-19 across Canada has not been well-described. We studied trends for patients with COVID-19-related acute respiratory distress syndrome who received ECMO. Methods: Multicentre retrospective cohort study using data from the Canadian Nosocomial Infection Surveillance Program across four different waves. Surveillance data was collected between March 2020 and June 2022. We reported data stratified by ECMO status and wave. Results: ECMO recipients comprised 299 (6.8%) of the 4,408 critically ill patients included. ECMO recipients were younger (median age 49 versus 62 years, p < 0.001), less likely to be vaccinated against COVID-19 (Wave 4 data: 5.3% versus 19%; p = 0.002), and had fewer comorbidities compared to patients who did not receive ECMO. Thirty-day all-cause mortality was similar between the ECMO and non-ECMO groups (23% versus 26%; p = 0.25). Among ECMO recipients, mortality tended to decrease across Waves 1 to 4: 48%, 31%, 18%, and 16%, respectively (p = 0.04 for trend). However, this was no longer statistically significant when removing the high mortality during Wave 1 (p = 0.15). Conclusions: Our findings suggest that critically ill patients in Canadian hospitals who received ECMO had different characteristics from those who did not receive ECMO. We also observed a trend of decreased mortality over the waves for the ECMO group. Possible explanatory factors may include potential delay in ECMO initiation during Wave 1, evolution of the virus, better understanding of COVID-19 disease and ECMO use, and new medical treatments and vaccines available in later waves. These findings may provide insight for future potential pandemics.

Historique: L'oxygénation extracorporelle en cas de COVID-19 n'est pas bien décrite au Canada. Les chercheurs ont étudié les tendances des patients ayant un syndrome respiratoire aigu lié à la COVID-19 qui ont reçu une oxygénation extracorporelle. Méthodologie: Étude de cohorte rétrospective multicentrique à l'aide de données du Programme canadien de surveillance des infections nosocomiales lors de quatre différentes vagues. Les chercheurs ont recueilli les données de surveillance de mars 2020 à juin 2022. Ils ont rendu compte des données stratifiées en fonction de l'état d'oxygénation extracorporelle et de la vague. Résultats: Les receveurs d'une oxygénation extracorporelle représentaient 299 (6,8 %) des 4 408 patients participants gravement malades. Ils étaient plus jeunes (âge médian de 49 ans par rapport à 62 ans, p<0,001), moins susceptibles d'être vaccinés contre la COVID-19 (données de la quatrième vague 4 : 5,3 % par rapport à 19 %; p=0,002) et présentaient moins d'autres maladies que les patients qui avaient reçu une oxygénation extracorporelle. La mortalité toutes causes confondues au bout de 30 jours était semblable entre le groupe sous oxygénation extracorporelle et celui sans oxygénation extracorporelle (23 % par rapport à 26 %; p=0,25). Chez les receveurs d'une oxygénation extracorporelle, la mortalité avait tendance à diminuer d'une vague à l'autre, soit de 48 %, 31 %, 18 % et 16 % entre la première et la quatrième vague, respectivement (p=0,04 par tendance). Cependant, ces résultats n'étaient plus statistiquement significatifs lorsqu'on excluait le taux de mortalité élevé observé pendant la première vague (p=0,15). Conclusions: Selon les observations des chercheurs, les patients gravement malades des hôpitaux canadiens qui avaient reçu une oxygénation extracorporelle présentaient des caractéristiques différentes de ceux qui n'en avaient pas reçu. Dans le groupe sous oxygénation extracorporelle, ils ont également observé une tendance vers une diminution de la mortalité entre les vagues. Les facteurs explicatifs possibles peuvent inclure un retard potentiel de l'initiation de l'oxygénation extracorporelle pendant la première vague, l'évolution du virus, une meilleure compréhension de la COVID-19, le recours à l'oxygénation extracorporelle, les nouveaux traitements médicaux et les vaccins offerts lors de vagues plus tardives. Ces observations pourraient donner des indications intéressantes lors de futures pandémies. Summary: COVID-19 has affected millions of people. Some patients with COVID-19 develop extremely severe disease requiring advanced critical care. Extracorporeal Membrane Oxygenation (ECMO) is an advanced potentially life-saving technique that can support patients whose lungs are unable to function properly despite using a ventilator (breathing machine). ECMO temporarily takes over lung function, essentially acting as external lungs. ECMO can allow time for the body to heal and potentially improve survival for patients with severe lung failure. The decision to use ECMO is complex and always made by a team of medical professionals who factor in the patient's overall health, medical conditions, and disease severity.We studied the trends for critically ill patients with COVID-19 who received ECMO across Canadian hospitals. We used data collected by trained health care professionals through a Canada-wide program that monitors infections in Canadian hospitals. We compared data between critically ill patients who received and did not receive ECMO, and by wave of the COVID-19 pandemic.Our data found that critically ill patients who received ECMO tended to be younger, have fewer medical conditions, and be less likely to be vaccinated against COVID-19. For patients who received ECMO, the mortality was highest in Wave 1 (48%), then Wave 2 (31%), and similar during Waves 3 and 4 (18% and 16%, respectively). Possible explanations for this trend include potential ECMO delay in Wave 1, the evolution of the virus, a better understanding of ECMO use for COVID-19 and available treatments and vaccines during later waves.In conclusion, our study highlights that critically ill patients who received ECMO in Canada had different features and traits compared to those who did not receive ECMO. As well, our study reported mortality across the waves, with possible explanations for the findings offered. These trends may be helpful in providing insight for future potential pandemics.

Evaluating the impact of a SIMPlified LaYered consent process on recruitment of potential participants to the Staphylococcus aureus Network Adaptive Platform trial: study protocol for a multicentre pragmatic nested randomised clinical trial (SIMPLY-SNAP trial).

INTRODUCTION: Informed consent forms (ICFs) for randomised clinical trials (RCTs) can be onerous and lengthy. The process has the potential to overwhelm patients with information, leading them to miss elements of the study that are critical for an informed decision. Specifically, overly long and complicated ICFs have the potential to increase barriers to trial participation for patients with mild cognitive impairment, those who do not speak English as a first language or among those with lower medical literacy. In turn, this can influence trial recruitment, completion and external validity. METHODS AND ANALYSIS: SIMPLY-SNAP is a pragmatic, multicentre, open-label, two-arm parallel-group superiority RCT, nested within a larger trial, the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. We will randomise potentially eligible participants of the SNAP trial 1:1 to a full-length ICF or a SIMPlified LaYered (SIMPLY) consent process where basic information is summarised with embedded hyperlinks to supplemental information and videos. The primary outcome is recruitment into the SNAP trial. Secondary outcomes include patient understanding of the clinical trial, patient and research staff satisfaction with the consent process, and time taken for consent. As an exploratory outcome, we will also compare measures of diversity (eg, gender, ethnicity), according to the consent process randomised to. The planned sample size will be 346 participants. ETHICS AND DISSEMINATION: The study has been approved by the ethics review board (Sunnybrook Health Sciences Research Ethics Board) at sites in Ontario. We will disseminate study results via the SNAP trial group and other collaborating clinical trial networks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06168474; www. CLINICALTRIALS: gov).

More Than a Decade Since the Latest CONSORT Non-inferiority Trials Extension: Do Infectious Diseases Trials Do Enough?

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.

Failure of scabies treatment: a systematic review and meta-analysis.

BACKGROUND: Treatment failure is considered to be an important factor in relation to the increase in scabies incidence over the last decade. However, the regional and temporal differences, in addition to the predictors of therapy failure, are unclear. OBJECTIVES: We aimed to conduct a systematic review of the prevalence of treatment failure in patients with scabies and investigation of associated factors. METHODS: We searched MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Global Health and the Cochrane Central Register of Controlled Trials from inception to August 2021 for randomized and quasi-randomized trials, in addition to observational studies that enrolled children or adults diagnosed with confirmed or clinical scabies treated with permethrin, ivermectin, crotamiton, benzyl benzoate, malathion, sulfur or lindane, and measured treatment failure or factors associated with treatment failure. We performed a random effects meta-analysis for all outcomes reported by at least two studies. RESULTS: A total of 147 studies were eligible for inclusion in the systematic review. The overall prevalence of treatment failure was 15.2% [95% confidence interval (CI) 12.9-17.6; I2 = 95.3%, moderate-certainty evidence] with regional differences between World Health Organization regions (P = 0.003) being highest in the Western Pacific region (26.9%, 95% CI 14.5-41.2). Oral ivermectin (11.8%, 95% CI 8.4-15.4), topical ivermectin (9.3%, 95% CI 5.1-14.3) and permethrin (10.8%, 95% CI 7.5-14.5) had relatively lower failure prevalence compared with the overall prevalence. Failure prevalence was lower in patients treated with two doses of oral ivermectin (7.1%, 95% CI 3.1-12.3) compared with those treated with one dose (15.2%, 95% CI 10.8-20.2; P = 0.021). Overall and permethrin treatment failure prevalence in the included studies (1983-2021) increased by 0.27% and 0.58% per year, respectively. Only three studies conducted a multivariable risk factor analysis; no studies assessed resistance. CONCLUSIONS: A second dose of ivermectin showed lower failure prevalence than single-dose ivermectin, which should be considered in all guidelines. The increase in treatment failure over time hints at decreasing mite susceptibility for several drugs, but reasons for failure are rarely assessed. Ideally, scabicide susceptibility testing should be implemented in future studies.

Conduct and reporting of multivariate network meta-analyses: a scoping review.

OBJECTIVES: Combining multivariate and network meta-analysis methods simultaneously in a multivariate network meta-analysis (MVNMA) provides the methodological framework to analyze the largest amount of evidence relevant to decision-makers (i.e., from indirect evidence and correlated outcomes). The objectives of this scoping review were to summarize the characteristics of MVNMAs published in the health sciences literature and map the methodological guidance available for MVNMA. STUDY DESIGN AND SETTING: We searched MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature from inception to 28 August 2023, along with citations of included studies, for quantitative evidence syntheses that applied MVNMA and articles addressing MVNMA methods. Pairs of reviewers independently screened potentially eligible studies. Collected data included bibliographic, methodological, and analytical characteristics of included studies. We reported results as total numbers, frequencies, and percentages for categorical variables and medians and interquartile ranges for continuous variables that were not normally distributed. RESULTS: After screening 1,075 titles and abstracts, and 112 full texts, we included 38 unique studies, of which, 10 were quantitative evidence syntheses that applied MVNMA and 28 were articles addressing MVNMA methods. Among the 10 MVNMAs, the first was published in 2013, four used studies identified from already published systematic reviews, and eight addressed pharmacological interventions, which were the most common interventions. They evaluated interventions for metastatic melanoma, colorectal cancer, prostate cancer, oral hygiene, disruptive behavior disorders, rheumatoid arthritis, narcolepsy, type 2 diabetes, and overactive bladder syndrome. Five MVNMAs analyzed two outcomes simultaneously, and four MVNMAs analyzed three outcomes simultaneously. Among the articles addressing MVNMA methods, the first was published in 2007 and the majority provided methodological frameworks for conducting MVNMAs (26/28, 93%). One study proposed criteria to standardize reporting of MVNMAs and two proposed items relevant to the quality assessment of MVNMAs. Study authors used data from 18 different illnesses to provide illustrative examples within their methodological guidance. CONCLUSIONS: The application of MVNMA in the health sciences literature is uncommon. Many methodological frameworks are published; however, standardization and specific criteria to guide reporting and quality assessment are lacking. This overview of the current landscape may help inform future conduct of MVNMAs and research on MVNMA methods.

Standard of care in advanced HIV disease: review of HIV treatment guidelines in six sub-Saharan African countries.

BACKGROUND: The World Health Organization (WHO) recommends an evidence-based package of care to reduce mortality and morbidity among people with advanced HIV disease (AHD). Adoption of these recommendations by national guidelines in sub-Saharan Africa is poorly documented. We aimed to review national guidelines for AHD management across six selected countries in sub-Saharan Africa for benchmarking against the 2021 WHO recommendations. METHODS: We reviewed national guidelines from six countries participating in an ongoing randomized controlled trial recruiting people with AHD. We extracted information addressing 18 items of AHD diagnosis and management across the following domains: [1] Definition of AHD, [2] Screening, [3] Prophylaxis, [4] Supportive care, and [5] HIV treatment. Data from national guideline documents were compared to the 2021 WHO consolidated guidelines on HIV and an agreement score was produced to evaluate extent of guideline adoption. RESULTS: The distribution of categories of agreement varied for the national documents. Four of the six countries addressed all 18 items (Malawi, Nigeria, Sierra Leone, Uganda). Overall agreement with the WHO 2021 guidelines ranged from 9 to 15.5 out of 18 possible points: Malawi 15.5 points, Nigeria, and Sierra Leone 14.5 points, South Africa 13.5 points, Uganda 13.0 points and Botswana with 9.0 points. Most inconsistencies were reported for the delay of antiretroviral therapy (ART) in presence of opportunistic diseases. None of the six national guidelines aligned with WHO recommendations around ART timing in patients with tuberculosis. Agreement correlated with the year of publication of the national guideline. CONCLUSION: National guidelines addressing the care of advanced HIV disease in sub-Saharan Africa are available. Besides optimal timing for start of ART in presence of tuberculosis, most national recommendations are in line with the 2021 WHO standards.

Equity issues rarely addressed in the development of COVID-19 formal recommendations and good practice statements: a cross-sectional study.

BACKGROUND AND OBJECTIVE: To identify COVID-19 actionable statements (e.g., recommendations) focused on specific disadvantaged populations in the living map of COVID-19 recommendations (eCOVIDRecMap) and describe how health equity was assessed in the development of the formal recommendations. METHODS: We employed the place of residence, race or ethnicity or culture, occupation, gender or sex, religion, education, socio-economic status, and social capital-Plus framework to identify statements focused on specific disadvantaged populations. We assessed health equity considerations in the evidence to decision frameworks (EtD) of formal recommendations for certainty of evidence and impact on health equity criteria according to the Grading of Recommendations, Assessment, Development, and Evaluations criteria. RESULTS: We identified 16% (124/758) formal recommendations and 24% (186/819) good practice statements (GPS) that were focused on specific disadvantaged populations. Formal recommendations (40%, 50/124) and GPS (25%, 47/186) most frequently focused on children. Seventy-six percent (94/124) of the recommendations were accompanied with EtDs. Over half (55%, 52/94) of those considered indirectness of the evidence for disadvantaged populations. Considerations in impact on health equity criterion most frequently involved implementation of the recommendation for disadvantaged populations (17%, 16/94). CONCLUSION: Equity issues were rarely explicitly considered in the development COVID-19 formal recommendations focused on specific disadvantaged populations. Guidance is needed to support the consideration of health equity in guideline development during health emergencies.

Methodological and Reporting Quality of Noninferiority Randomized Controlled Trials Comparing Antiretroviral Therapies: A Systematic Review.

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.

Trends in Severe Outcomes Among Adult and Pediatric Patients Hospitalized With COVID-19 in the Canadian Nosocomial Infection Surveillance Program, March 2020 to May 2022.

Importance: Trends in COVID-19 severe outcomes have significant implications for the health care system and are key to informing public health measures. However, data summarizing trends in severe outcomes among patients hospitalized with COVID-19 in Canada are not well described. Objective: To describe trends in severe outcomes among patients hospitalized with COVID-19 during the first 2 years of the COVID-19 pandemic. Design, Setting, and Participants: Active prospective surveillance in this cohort study was conducted from March 15, 2020, to May 28, 2022, at a sentinel network of 155 acute care hospitals across Canada. Participants included adult (aged ≥18 years) and pediatric (aged 0-17 years) patients hospitalized with laboratory-confirmed COVID-19 at a Canadian Nosocomial Infection Surveillance Program (CNISP)-participating hospital. Exposures: COVID-19 waves, COVID-19 vaccination status, and age group. Main Outcomes and Measures: The CNISP collected weekly aggregate data on the following severe outcomes: hospitalization, admission to an intensive care unit (ICU), receipt of mechanical ventilation, receipt of extracorporeal membrane oxygenation, and all-cause in-hospital death. Results: Among 1 513 065 admissions, the proportion of adult (n = 51 679) and pediatric (n = 4035) patients hospitalized with laboratory-confirmed COVID-19 was highest in waves 5 and 6 of the pandemic compared with waves 1 to 4 (77.3 vs 24.7 per 1000 patient admissions). Despite this, the proportion of patients with positive test results for COVID-19 who were admitted to an ICU, received mechanical ventilation, received extracorporeal membrane oxygenation, and died were each significantly lower in waves 5 and 6 when compared with waves 1 through 4. Admission to the ICU and in-hospital all-cause death rates were significantly higher among those who were unvaccinated against COVID-19 when compared with those who were fully vaccinated (incidence rate ratio, 4.3 and 3.9, respectively) or fully vaccinated with an additional dose (incidence rate ratio, 12.2 and 15.1, respectively). Conclusions and Relevance: The findings of this cohort study of patients hospitalized with laboratory-confirmed COVID-19 suggest that COVID-19 vaccination is important to reduce the burden on the Canadian health care system as well as severe outcomes associated with COVID-19.

SARS-CoV-2 Outbreak Investigation Using Contact Tracing and Whole-Genome Sequencing in an Ontario Tertiary Care Hospital.

Genomic epidemiology can facilitate an understanding of evolutionary history and transmission dynamics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak. We used next-generation sequencing techniques to study SARS-CoV-2 genomes isolated from patients and health care workers (HCWs) across five wards of a Canadian hospital with an ongoing SARS-CoV-2 outbreak. Using traditional contact tracing methods, we show transmission events between patients and HCWs, which were also supported by the SARS-CoV-2 lineage assignments. The outbreak predominantly involved SARS-CoV-2 B.1.564.1 across all five wards, but we also show evidence of community introductions of lineages B.1, B.1.1.32, and B.1.231, falsely assumed to be outbreak related. Altogether, our study exemplifies the value of using contact tracing in combination with genomic epidemiology to understand the transmission dynamics and genetic underpinnings of a SARS-CoV-2 outbreak. IMPORTANCE Our manuscript describes a SARS-CoV-2 outbreak investigation in an Ontario tertiary care hospital. We use traditional contract tracing paired with whole-genome sequencing to facilitate an understanding of the evolutionary history and transmission dynamics of this SARS-CoV-2 outbreak in a clinical setting. These advancements have enabled the incorporation of phylogenetics and genomic epidemiology into the understanding of clinical outbreaks. We show that genomic epidemiology can help to explore the genetic evolution of a pathogen in real time, enabling the identification of the index case and helping understand its transmission dynamics to develop better strategies to prevent future spread of SARS-CoV-2 in congregate, clinical settings such as hospitals.

GloveCare: a pilot study in preparation for a cluster crossover randomized controlled trial of non-sterile glove-based care in preventing late-onset infection in the NICU.

BACKGROUND: Late-onset infections (LOI) are a major cause of morbidity and mortality among patients in the neonatal intensive care unit (NICU). Gloving after hand hygiene may be a pragmatic approach to prevent infections that arise when healthcare workers' hands transmit pathogens to neonates. OBJECTIVE: To determine the feasibility of conducting a multicenter, open-labeled randomized controlled trial (RCT) to determine whether a protocol that requires healthcare workers (HCWs) in a level 3 NICU to wear non-sterile gloves plus hand hygiene reduces the occurrence of a late-onset infection, compared to hand hygiene alone. METHODS: In this single-center pilot study, we recruited neonates admitted to the McMaster Children's Hospital NICU from June 2017 to May 2018. The NICU was randomized to begin with the standard (control) arm for 6 months (June 2017 to Dec 2017), followed by the gloving (GloveCare) arm for 6 months (Jan 2018 to July 2018), with a 2-week washout period in-between to educate healthcare workers about gloving. We measured numerous feasibility outcomes including enrollment, event rate, and compliance with hand hygiene (Moment 1: before patient contact, Moment 2: before clean procedure, Moment 3: after body fluid contact, Moment 4: after patient contact) and gloving compliance. RESULTS: We enrolled 750 neonates (390 Standard care, 360 GloveCare) and achieved 100% enrollment. We found higher hand hygiene compliance during the standard care arm compared to the GloveCare for all four moments of hand hygiene (Moment 1: 87% vs 79%, OR=1.86 (1.34, 2.59); Moment 2: OR=1.73 (1.00, 3.01); Moment 3: OR=1.11 (0.62, 1.98); Moment 4: OR=1.65 (1.27, 2.14)). We developed and validated a method to calculate glove compliance, which ranged from 48 to 85%, and was highest for moment 3 (doffing after a procedure or body fluid exposure risk). No adverse events were documented for patients or staff. DISCUSSION: Reduction in hand hygiene compliance in the GloveCare arm presents a pragmatic challenge in ascertaining the effectiveness of gloving to prevent LOI. Most LOIs were non-sterile-site infections, which is considered a less patient-important or clinically relevant outcome compared to sterile-site LOI. Ensuring efficient collection and validation of hand hygiene and gloving data is imperative. CONCLUSION: The pilot study demonstrated the feasibility of this intervention though modifications to improve hand hygiene compliance during GloveCare will be important prior to a multicenter cluster RCT to assess the efficacy of non-sterile glove-based care in preventing LOI in the NICU. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03078335.

Comparison of three dosing intervals for the primary vaccination of the SARS-CoV-2 mRNA Vaccine (BNT162b2) on magnitude, neutralization capacity and durability of the humoral immune response in health care workers: A prospective cohort study.

OBJECTIVES: The dosing interval of a primary vaccination series can significantly impact on vaccine immunogenicity and efficacy. The current study compared 3 dosing intervals for the primary vaccination series of the BNT162b2 mRNA COVID-19 vaccine, on humoral immune response and durability against SARS-CoV-2 ancestral and Beta variants up to 9 months post immunization. METHODS: Three groups of age- and sex-matched healthcare workers (HCW) who received 2 primary doses of BNT162b2 separated by 35-days, 35-42 days or >42-days were enrolled. Vaccine induced antibody titers at 3 weeks, 3 and 6-9 months post-second dose were assessed. RESULTS: There were 309 age- and sex-matched HCW (mean age 43 [sd 13], 58% females) enrolled. Anti-SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibody titers showed significant waning in levels beyond 35 days post first dose. The second dose induced a significant rise in antibody titers, which peaked at 3 weeks and then declined at variable rates across groups. The magnitude, consistency and durability of response was greater for anti-Spike than anti-RBD antibodies; and for IgG than IgA or IgM. Compared to the shorter schedules, a longer interval of >42 days offered the highest binding and neutralizing antibody titers against SARS-CoV-2 ancestral and Beta (B1.351) variants beyond 3 months post-vaccination. CONCLUSIONS: This is the first comprehensive study to compare 3 dosing intervals for the primary vaccination of BNT162b2 mRNA COVID-19 vaccine implemented in the real world. These findings suggest that delaying the second dose beyond 42 days can potentiate and prolong the humoral response against ancestral and Beta variants of SARS-CoV-2 up to 9 months post-vaccination.

Determining coronavirus disease 2019 (COVID-19) community incidence threshold for preoperative testing.

Preprocedural testing for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) is frequently used to reduce perioperative morbidity and mortality during the pandemic. Such testing is resource intensive, and the relative benefits depend on local epidemiology. We propose a threshold of 20 per 100,000 unlinked cases to activate such testing to optimize the yield and positive predictive value.

Trends in Clostridioides difficile infection rates in Canadian hospitals during the coronavirus disease 2019 (COVID-19) pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

Nirmatrelvir-ritonavir use among adults hospitalized with COVID-19 during the Omicron phase of the COVID-19 pandemic, Canadian Nosocomial Infection Surveillance Program.

Background: Recent studies have demonstrated the effectiveness of nirmatrelvir-ritonavir in reducing the risk of progression to severe disease among outpatients with mild to moderate coronavirus disease 2019 (COVID-19); however, data are limited regarding the use and role of nirmatrelvir-ritonavir among hospitalized patients. This study describes the use and outcomes of nirmatrelvir-ritonavir among adults hospitalized with COVID-19 in a sentinel network of Canadian acute care hospitals during the Omicron variant phase of the pandemic. Methods: The Canadian Nosocomial Infection Surveillance Program conducts surveillance of hospitalized patients with COVID-19 in acute care hospitals across Canada. Demographic, clinical, treatment and 30-day outcome data were collected by chart review by trained infection control professionals using standardized questionnaires. Results: From January 1 to December 31, 2022, 13% (n=490/3,731) of adult patients (18 years of age and older) hospitalized with COVID-19 in 40 acute care hospitals received nirmatrelvir-ritonavir either at admission or during hospitalization. Most inpatients who received nirmatrelvir-ritonavir, 79% of whom were fully vaccinated, had at least one pre-existing comorbidity (97%) and were of advanced age (median=79 years). Few were admitted to an intensive care unit (2.3%) and among the 490 nirmatrelvir-ritonavir treated inpatients, there were 13 (2.7%) deaths attributable to COVID-19. Conclusion: These findings from a large sentinel network of Canadian acute-care hospitals suggest that nirmatrelvir-ritonavir is being used to treat adult COVID-19 patients at admission who are at risk of progression to severe disease or those who acquired COVID-19 in hospital. Additional research on the efficacy and indications for nirmatrelvir-ritonavir use in hospitalized patients is warranted to inform future policies and guidelines.