COVID-19 vaccine uptake among Ontario physicians: a descriptive population-based retrospective cohort study.

OBJECTIVES: To determine COVID-19 vaccine uptake among physicians in Ontario, Canada from 14 December 2020 to 13 February 2022. DESIGN: Population-based retrospective cohort study. SETTING: All registered physicians in Ontario, Canada using data from linked provincial administrative healthcare databases. PARTICIPANTS: 41 267 physicians (including postgraduate trainees) who were Ontario residents and registered with the College of Physicians and Surgeons of Ontario were included. Physicians who were out of province, had not accessed Ontario Health Insurance Plan-insured services for their own care for ≥5 years and those with missing identifiers were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were the proportions of physicians who were recorded to have received at least one, at least two and three doses of a Health Canada-approved COVID-19 vaccine by study end date. Secondary outcomes were how uptake varied by physician characteristics (including age, sex, specialty and residential location) and time elapsed between doses. RESULTS: Of 41 267 physicians, (56% male, mean age 47 years), 39 359 (95.4%) received at least one dose, 39 148 (94.9%) received at least two doses and 35 834 (86.8%) received three doses of a COVID-19 vaccine. Of those who received three doses, the proportions were 90.4% among those aged ≥60 years and 81.2-89.5% among other age groups; 88.7% among family physicians and 89% among specialists. 1908 physicians (4.6%) had no record of vaccination, and this included 3.4% of family physicians and 4.1% of specialists; however, 28% of this group had missing specialty information. CONCLUSIONS: In Ontario, within 14 months of COVID-19 vaccine availability, 86.8% of physicians had three doses of a COVID-19 vaccine, compared with 45.6% of the general population. Findings may signify physicians' confidence in the safety and effectiveness of COVID-19 vaccines.

Mailed feedback to primary care physicians on antibiotic prescribing for patients aged 65 years and older: pragmatic, factorial randomised controlled trial.

OBJECTIVES: To evaluate whether providing family physicians with feedback on their antibiotic prescribing compared with that of their peers reduces antibiotic prescriptions. To also identify effects on antibiotic prescribing from case-mix adjusted feedback reports and messages emphasising antibiotic associated harms. DESIGN: Pragmatic, factorial randomised controlled trial. SETTING: Primary care physicians in Ontario, Canada PARTICIPANTS: All primary care physicians were randomly assigned a group if they were eligible and actively prescribing antibiotics to patients 65 years or older. Physicians were excluded if had already volunteered to receive antibiotic prescribing feedback from another agency, or had opted out of the trial. INTERVENTION: A letter was mailed in January 2022 to physicians with peer comparison antibiotic prescribing feedback compared with the control group who did not receive a letter (4:1 allocation). The intervention group was further randomised in a 2x2 factorial trial to evaluate case-mix adjusted versus unadjusted comparators, and emphasis, or not, on harms of antibiotics. MAIN OUTCOME MEASURES: Antibiotic prescribing rate per 1000 patient visits for patients 65 years or older six months after intervention. Analysis was in the modified intention-to-treat population using Poisson regression. RESULTS: 5046 physicians were included and analysed: 1005 in control group and 4041 in intervention group (1016 case-mix adjusted data and harms messaging, 1006 with case-mix adjusted data and no harms messaging, 1006 unadjusted data and harms messaging, and 1013 unadjusted data and no harms messaging). At six months, mean antibiotic prescribing rate was 59.4 (standard deviation 42.0) in the control group and 56.0 (39.2) in the intervention group (relative rate 0.95 (95% confidence interval 0.94 to 0.96). Unnecessary antibiotic prescribing (0.89 (0.86 to 0.92)), prolonged duration prescriptions defined as more than seven days (0.85 (0.83 to 0.87)), and broad spectrum prescribing (0.94 (0.92 to 0.95)) were also significantly lower in the intervention group compared with the control group. Results were consistent at 12 months post intervention. No significant effect was seen for including emphasis on harms messaging. A small increase in antibiotic prescribing with case-mix adjusted reports was noted (1.01 (1.00 to 1.03)). CONCLUSIONS: Peer comparison audit and feedback letters significantly reduced overall antibiotic prescribing with no benefit of case-mix adjustment or harms messaging. Antibiotic prescribing audit and feedback is a scalable and effective intervention and should be a routine quality improvement initiative in primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04594200.

The Effect of COVID-19 Vaccination on Outpatient Antibiotic Prescribing in Older Adults: A Self-Controlled Risk-Interval Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination has been associated with reduced outpatient antibiotic prescribing among older adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the impact of COVID-19 vaccination on outpatient antibiotic prescribing in the broader population of older adults, regardless of SARS-CoV-2 infection status. METHODS: We included adults aged ≥65 years who received their first, second, and/or third COVID-19 vaccine dose from December 2020 to December 2022. We used a self-controlled risk-interval design and included cases who received an antibiotic prescription 2-6 weeks before vaccination (pre-vaccination or control interval) or after vaccination (post-vaccination or risk interval). We used conditional logistic regression to estimate the odds of being prescribed (1) any antibiotic, (2) a typical "respiratory" infection antibiotic, or (3) a typical "urinary tract" infection antibiotic (negative control) in the post-vaccination interval versus the pre-vaccination interval. We accounted for temporal changes in antibiotic prescribing using background monthly antibiotic prescribing counts. RESULTS: 469 923 vaccine doses met inclusion criteria. The odds of receiving any antibiotic or a respiratory antibiotic prescription were lower in the post-vaccination versus pre-vaccination interval (aOR, .973; 95% CI, .968-.978; aOR, .961; 95% CI, .953-.968, respectively). There was no association between vaccination and urinary antibiotic prescriptions (aOR, .996; 95% CI, .987-1.006). Periods with high (>10%) versus low (<5%) SARS-CoV-2 test positivity demonstrated greater reductions in antibiotic prescribing (aOR, .875; 95% CI, .845-.905; aOR, .996; 95% CI, .989-1.003, respectively). CONCLUSIONS: COVID-19 vaccination was associated with reduced outpatient antibiotic prescribing in older adults, especially during periods of high SARS-CoV-2 circulation.

Association between infectious diseases consultation and mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: Data supporting routine infectious diseases (ID) consultation in Gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. METHODS: Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure. RESULTS: Of 30,159 patients with GN-BSI across 53 hospitals, 11,013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7-76.1%, interquartile range 19.6-41.1%). 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully-adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted HR 0.82, 95% CI 0.77-0.88, p < 0.0001; translating to absolute risk reduction of -3.8% or NNT of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). CONCLUSIONS: Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes.

A multiprovincial retrospective analysis of the incidence of myocarditis or pericarditis after mRNA vaccination compared to the incidence after SARS-CoV-2 infection.

Objective: To compare myocarditis/pericarditis risk after COVID-19 mRNA vaccination versus SARS-CoV-2 infection, and to assess if myocarditis/pericarditis risk varies by vaccine dosing interval. Methods: In this retrospective cohort study, we used linked databases in Quebec, Ontario, and British Columbia between January 26, 2020, and September 9, 2021. We included individuals aged 12 or above who received an mRNA vaccine as the second dose or were SARS-CoV-2-positive by RT-PCR. The outcome was hospitalization/emergency department visit for myocarditis/pericarditis within 21 days of exposure. We calculated age- and sex-stratified incidence ratios (IRs) of myocarditis/pericarditis following mRNA vaccination versus SARS-CoV-2 infection. We also calculated myocarditis/pericarditis incidence by vaccine type, homologous/heterologous schedule, and dosing interval. We pooled province-specific estimates using meta-analysis. Results: Following 18,860,817 mRNA vaccinations and 860,335 SARS-CoV-2 infections, we observed 686 and 160 myocarditis/pericarditis cases, respectively. Myocarditis/pericarditis incidence was lower after vaccination than infection (IR [BNT162b2/SARS-CoV-2], 0.14; 95%CI, 0.07-0.29; IR [mRNA-1273/SARS-CoV-2], 0.28; 95%CI, 0.20-0.39). Within the vaccinated cohort, myocarditis/pericarditis incidence was lower with longer dosing intervals; IR (56 or more days/15-30 days) was 0.28 (95%CI, 0.19-0.41) for BNT162b2 and 0.26 (95%CI, 0.18-0.38) for mRNA-1273. Conclusion: Myocarditis/pericarditis risk was lower after mRNA vaccination than SARS-CoV-2 infection, and with longer intervals between primary vaccine doses.

Follow-up blood cultures do not reduce mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: The utility of follow-up blood cultures (FUBCs) in patients with Gram-negative bloodstream infection (GN-BSI) is controversial. Observational studies have suggested significant mortality benefit but may be limited by single-centre designs, immortal time bias, and residual confounding. We examined the impact of FUBCs on mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario, Canada. METHODS: Adult patients with GN-BSI hospitalized between April 2017 and December 2021 were included. Primary outcome was all-cause mortality within 30 days. FUBC was treated as a time-varying exposure. Secondary outcomes were 90-day mortality, length of stay, and number of days alive and out of hospital at 30 and 90 days. RESULTS: Thirty-four thousand one hundred patients were included; 8807 (25.8%) patients received FUBC, of which 966 (11.0%) were positive. Median proportion of patients receiving FUBC was 18.8% (interquartile range, 10.0-29.7%; range, 0-66.1%) across 101 hospitals; this correlated with positivity and contamination rate. Eight hundred ninety (10.1%) patients in the FUBC group and 2263 (8.9%) patients in the no FUBC group died within 30 days. In the fully adjusted model, there was no association between FUBC and mortality (hazard ratio, 0.97; 95% CI, 0.90-1.04). Patients with FUBC had significantly longer length of stay (median, 11 vs. 7 days; adjusted risk ratio, 1.18; 95% CI, 1.16-1.21) and fewer number of days alive and out of hospital at 30 and 90 days. DISCUSSION: FUBC collection in patients with GN-BSI varies widely across hospitals and may be associated with prolonged hospitalization without clear survival benefit. Residual confounding may be present given the observational design. Clear benefit should be demonstrated in a randomized trial before widespread adoption of routine FUBC.

Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19.

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) (aORper 28 days = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aORper 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.

A Canadian children's hospital's experience with cystic echinococcosis over 30 years: A case series.

Background: Cystic echinococcosis (CE) or hydatid disease caused by the cestode Echinococcus granulosus sensu lato is an uncommon infection in Canada especially among children. There are limited reports describing the clinical presentation and management in Canadian children. Methods: The medical records of all children diagnosed with CE at a quaternary paediatric centre in Ontario between January 1988 and August 2021 were retrospectively reviewed. The clinical course, management, and outcomes of each case were summarized. Results: We report two paediatric cases of cystic echinococcosis (CE) in detail and review four additional cases seen at our institution over 33.5 years. The first case was a previously healthy 12-year-old boy with pulmonary CE resulting in unilateral lung collapse and mediastinal shift, who was presumedly infected while living in the Middle East. The second case was a previously healthy 3-year-old girl with pulmonary CE acquired locally in southern Ontario. Four other cases of CE with hepatic involvement (median age 12.5 years) were identified during the study period. Five out of six patients received both surgical and medical therapy. Conclusion: CE is a rare but serious disease seen in southern Canada that has historically been associated with travel or migration. Due to changes in urban wildlife landscapes and increased global migration, CE may become more prevalent in Canadian children. We describe the first locally acquired case in rural southern Ontario diagnosed at our centre. Prompt recognition of this infection in children by health care providers is important to prevent morbidity and mortality.

Historique: L'échinococcose kystique (ÉK), ou hydatidose, causée par le cestode Echinococcus granulosus sensu lato, est une infection peu courante au Canada, particulièrement chez les enfants. Peu de rapports en décrivent la présentation clinique et la prise en charge chez les enfants canadiens. Méthodologie: Les auteurs ont procédé à l'analyse rétrospective des dossiers médicaux de tous les enfants ayant reçu un diagnostic d'ÉK dans un centre pédiatrique de soins quaternaires ontarien entre janvier 1988 et août 2021. Ils ont résumé l'évolution clinique, la prise en charge et le résultat clinique de chaque cas. Résultats: Les auteurs font un compte rendu détaillé de deux cas pédiatriques d'ÉK et analysent quatre autres cas observés à leur établissement sur une période de 33,5 ans. Le premier cas d'ÉK pulmonaire a touché un garçon de 12 ans auparavant en santé, probablement infecté alors qu'il habitait au Moyen-Orient, et a entraîné un collapsus pulmonaire unilatéral et une déviation médiastinale. Le deuxième cas d'ÉK pulmonaire a été observé chez une fillette de trois ans auparavant en santé qui a été infectée dans le sud de l'Ontario. Les auteurs ont relevé quatre autres cas d'ÉK comportant une atteinte hépatique (âge médian de 12,5 ans) pendant la période de l'étude. Cinq des six patients ont reçu à la fois un traitement chirurgical et médical. Conclusion: L'ÉK est une maladie rare, mais grave dans le sud du Canada. Elle était auparavant associée à un voyage ou une migration. En raison des changements aux paysages fauniques urbains et de la migration mondiale accrue, elle pourrait devenir plus prévalente chez les enfants canadiens. Les auteurs décrivent les premiers cas d'acquisition dans les régions rurales du sud de l'Ontario, diagnostiqués à leur centre. Il est important que les dispensateurs de soins dépistent cette infection rapidement chez les enfants pour éviter la morbidité et la mortalité.

Documenting the indication for antimicrobial prescribing: A retrospective observational study of long-term care homes.

BACKGROUND: Overuse of antimicrobials in residents of long-term care homes is common and can result in harm. Antimicrobial stewardship interventions are needed in the long-term care (LTC) homes setting to improve the appropriate use of antimicrobials. Previous literature has highlighted the importance of documenting antimicrobial indication as a strategy that contributes to improve antimicrobial use; however, there is a lack of evidence in LTC homes. This study examines the prevalence, clarity, and facility-level variability of antibiotic indication documentation in this setting. METHODS: This is an observational retrospective study of oral antibiotic prescriptions dispensed to 218 homes between January 1, 2021 and December 31, 2022 in Ontario, Canada. Indication was obtained from reviewing antibiotic prescription data. Clarity was determined by comparing documented indication to the National Antimicrobial Prescribing Survey (NAPS). Descriptive analysis was performed to examine the prevalence and clarity of indication documentation. Funnel plots were generated to examine variability in prevalence of indication documentation and clarity at the home level. RESULTS: Overall, 22.9% (7998/34,867) of prescriptions had an indication documented. The proportion of indications that were clear was 37% (2984/7998). The most common indications were for urinary (45%), skin and soft tissue (19.9%) and respiratory infections (15.0%). At the home level, the median prevalence of indication was 19.6% (interquartile range [IQR]: 10.8%-31.4%) and median prevalence of clear indications was 35.1% (IQR: 23.8%-42.9%). Funnel plots revealed substantial variability in indication prevalence with 46.3% of homes falling outside of 99% limits but minimal variability in indication clarity between homes with only 8.7% of homes outside of 99% control limits. CONCLUSIONS: There is an opportunity to increase both the prevalence and clarity of antibiotic prescriptions in LTC homes. Future work should focus on determining how best to support prescription indication documentation in this setting with consideration being given to prescription workflow and most common antibiotic prescription indications.

Effectiveness of mRNA COVID-19 Monovalent and Bivalent Vaccine Booster Doses Against Omicron Severe Outcomes Among Adults Aged ≥50 Years in Ontario, Canada: A Canadian Immunization Research Network Study.

We estimated the effectiveness of booster doses of monovalent and bivalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults aged ≥50 years in Ontario, Canada. Monovalent and bivalent mRNA COVID-19 booster doses provided similar strong initial protection against severe outcomes. Uncertainty remains around waning of protection from these vaccines.

Viral dynamics of the SARS-CoV-2 Omicron Variant in Paediatric Patients; A prospective cohort study.

BACKGROUND: There are limited data on the viral dynamics of SARS-CoV-2 in children. Understanding viral load changes over the course of illness and duration of viral shedding may provide insight into transmission dynamics to inform public health and infection control decisions. METHODS: We conducted a prospective cohort study of children 18 years and younger with PCR confirmed SARS-CoV-2 between February 1, 2022 and March 14, 2022. SARS-CoV-2 testing occurred on daily samples for 10 days; a subset of participants completed daily rapid antigen testing (RAT). Viral RNA trajectories were described in relation to symptom onset and resolution. The associations between both time since symptom onset/resolution and non-infectious viral load were evaluated using a Cox proportional hazards model. FINDINGS: Among 101 children aged 2 to 17 years, the median time to study-defined non-infectious viral load was 5 days post symptom onset, with 75% meeting this threshold by 7 days, and 90% by 10 days. On the day of and day after symptom resolution, 43 of 87 (49%) and 52 (60%) had met the non-infectious thresholds, respectively. Of the 50 participants completing RAT, positivity at symptom onset and on the day after symptom onset was 67% (16/24) and 75% (14/20). On the first day where the non-infectious threshold was met, 61% (n = 27/44) of participant RAT results were positive. INTERPRETATION: Children often met the study-defined non-infectiousness threshold on the day after symptom resolution. RAT tests were often negative early in the course of illness and should not be relied on to exclude infection. CLINICAL TRIALS REGISTRATION: NCT05240183.

The impact of the COVID-19 pandemic on blood culture practices and bloodstream infections.

IMPORTANCE: Bacterial infections are a significant cause of morbidity and mortality worldwide. In the wake of the COVID-19 pandemic, previous studies have demonstrated pandemic-related shifts in the epidemiology of bacterial bloodstream infections (BSIs) in the general population and in specific hospital systems. Our study uses a large, comprehensive data set stratified by setting [community, long-term care (LTC), and hospital] to uniquely demonstrate how the effect of the COVID-19 pandemic on BSIs and testing practices varies by healthcare setting. We showed that, while the number of false-positive blood culture results generally increased during the pandemic, this effect did not apply to hospitalized patients. We also found that many infections were likely under-recognized in patients in the community and in LTC, demonstrating the importance of maintaining healthcare for these groups during crises. Last, we found a decrease in infections caused by certain pathogens in the community, suggesting some secondary benefits of pandemic-related public health measures.

Protection conferred by COVID-19 vaccination, prior SARS-CoV-2 infection, or hybrid immunity against Omicron-associated severe outcomes among community-dwelling adults.

INTRODUCTION: We assessed protection from COVID-19 vaccines and/or prior SARS-CoV-2 infection against Omicron-associated severe outcomes during successive sublineage-predominant periods. METHODS: We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, PCR-tested adults aged ≥50 years in Ontario, Canada between January 2, 2022 and June 30, 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2-5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection. RESULTS: We included 18,526 cases with Omicron-associated severe outcomes and 90,778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance, but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose, 6-month: 68%, 95%CI 63%-72%; fourth-dose, 6-month: 80%, 95%CI 77%-83%), but was lower and waned quickly during BQ/XBB predominance (third-dose, 6-month: 59%, 95%CI 48%-67%; 12-month: 49%, 95%CI 41%-56%; fourth-dose, 6-month: 62%, 95%CI 56%-68%, 12-months: 51%, 95%CI 41%-56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance, but was reduced during BQ/XBB predominance (third-dose, 6-month: 60%, 95%CI 36%-75%; fourth-dose, 6-month: 63%, 95%CI 42%-76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95%CI 79%-96%). Prior infection alone did not confer lasting protection. CONCLUSION: Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review.

Variability in changes in physician outpatient antibiotic prescribing from 2019 to 2021 during the COVID-19 pandemic in Ontario, Canada.

Objective: To evaluate inter-physician variability and predictors of changes in antibiotic prescribing before (2019) and during (2020/2021) the coronavirus disease 2019 (COVID-19) pandemic. Methods: We conducted a retrospective cohort analysis of physicians in Ontario, Canada prescribing oral antibiotics in the outpatient setting between January 1, 2019 and December 31, 2021 using the IQVIA Xponent data set. The primary outcome was the change in the number of antibiotic prescriptions between the prepandemic and pandemic period. Secondary outcomes were changes in the selection of broad-spectrum agents and long-duration (>7 d) antibiotic use. We used multivariable linear regression models to evaluate predictors of change. Results: There were 17,288 physicians included in the study with substantial inter-physician variability in changes in antibiotic prescribing (median change of -43.5 antibiotics per physician, interquartile range -136.5 to -5.0). In the multivariable model, later career stage (adjusted mean difference [aMD] -45.3, 95% confidence interval [CI] -52.9 to -37.8, p < .001), family medicine (aMD -46.0, 95% CI -62.5 to -29.4, p < .001), male patient sex (aMD -52.4, 95% CI -71.1 to -33.7, p < .001), low patient comorbidity (aMD -42.5, 95% CI -50.3 to -34.8, p < .001), and high prescribing to new patients (aMD -216.5, 95% CI -223.5 to -209.5, p < .001) were associated with decreases in antibiotic initiation. Family medicine and high prescribing to new patients were associated with a decrease in selection of broad-spectrum agents and prolonged antibiotic use. Conclusions: Antibiotic prescribing changed throughout the COVID-19 pandemic with overall decreases in antibiotic initiation, broad-spectrum agents, and prolonged antibiotic courses with inter-physician variability. These findings present opportunities for community antibiotic stewardship interventions.

Effectiveness of maternal influenza vaccination during pregnancy against laboratory-confirmed seasonal influenza among infants under 6 months of age in Ontario, Canada.

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 2010-2019 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, 1,783 (7.5%) were positive and 1,708 (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 (1st/2nd: 66%, 40%-80%; 3rd: 63%, 46%-74%), infant age at testing (0-<2 months: 63%, 46%-75%; 2-<6 months: 64%, 36%-79%), and gestational age at birth (≥37 weeks: 64%, 50%-75%; < 37 weeks: 61%, 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.

Newborn and Early Infant Outcomes Following Maternal COVID-19 Vaccination During Pregnancy.

Importance: The study team previously showed that maternal mRNA COVID-19 vaccination during pregnancy confers protection against SARS-CoV-2 infection and COVID-19-related hospital admission in newborns and young infants. In this study, the study team evaluated newborn and early infant safety outcomes following maternal messenger RNA (mRNA) COVID-19 vaccination during pregnancy, for which there is limited comparative epidemiological evidence. Objective: To determine if maternal mRNA COVID-19 vaccination during pregnancy is associated with adverse newborn and early infant outcomes. Design, Setting, and Participants: This population-based retrospective cohort study took place in Ontario, Canada, using multiple linked health administrative databases. Singleton live births with an expected delivery date between May 1, 2021, and September 2, 2022, were included. Data were analyzed from January 2023 through March 2023. Exposure: Maternal mRNA COVID-19 vaccination (1 or more doses) during pregnancy. Main Outcomes and Measures: Severe neonatal morbidity (SNM), neonatal death, neonatal intensive care unit (NICU) admission, neonatal readmission, and hospital admission up to 6 months of age. The study team calculated inverse probability of treatment weighted risk ratios (RRs) and fit weighted Cox proportional hazards regression models comparing outcomes in infants of mothers who received COVID-19 vaccination during pregnancy with those who received no COVID-19 vaccine doses before delivery. Results: In total, 142 006 infants (72 595 male [51%]; mean [SD] gestational age at birth, 38.7 [1.7] weeks) were included; 85 670 were exposed to 1 or more COVID-19 vaccine doses in utero (60%). Infants of vaccinated mothers had lower risks of SNM (vaccine exposed 7.3% vs vaccine unexposed 8.3%; adjusted RR [aRR], 0.86; 95% CI, 0.83-0.90), neonatal death (0.09% vs 0.16%; aRR, 0.47; 95% CI, 0.33-0.65), and NICU admission (11.4% vs 13.1%; aRR, 0.86; 95% CI, 0.83-0.89). There was no association between maternal vaccination during pregnancy and neonatal readmission (5.5% vs 5.1%; adjusted hazard ratio, 1.03; 95% CI, 0.98-1.09) or 6-month hospital admission (8.4% vs 8.1%; adjusted hazard ratio, 1.01; 95% CI, 0.96-1.05). Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, maternal mRNA COVID-19 vaccination during pregnancy was associated with lower risks of SNM, neonatal death, and NICU admission. In addition, neonatal and 6-month readmissions were not increased in infants of mothers vaccinated during pregnancy.

Antibiotic prescribing guideline recommendations in COVID-19: a systematic survey.

Background: COVID-19 and antimicrobial resistance (AMR) are two intersecting public health crises. Antimicrobial overuse in patients with COVID-19 threatens to worsen AMR. Guidelines are fundamental in encouraging antimicrobial stewardship. We sought to assess the quality of antibiotic prescribing guidelines and recommendations in the context of COVID-19, and whether they incorporate principles of antimicrobial stewardship. Methods: We performed a systematic survey which included a search using the concepts "antibiotic/antimicrobial" up to November 15, 2022 of the eCOVID-19 living map of recommendations (RecMap) which aggregates guidelines across a range of international sources and all languages. Guidelines providing explicit recommendations regarding antibacterial use in COVID-19 were eligible for inclusion. Guideline and recommendation quality were assessed using the AGREE II and AGREE-REX instruments, respectively. We extracted guideline characteristics including panel representation and the presence or absence of explicit statements related to antimicrobial stewardship (i.e., judicious antibiotic use, antimicrobial resistance or adverse effects as a consequence of antibiotic use). We used logistic regression to evaluate the relationship between guideline characteristics including quality and incorporation of antimicrobial stewardship principles. Protocol registration (OSF): https://osf.io/4pgtc. Findings: Twenty-eight guidelines with 63 antibiotic prescribing recommendations were included. Recommendations focused on antibiotic initiation (n = 52, 83%) and less commonly antibiotic selection (n = 13, 21%), and duration of therapy (n = 15, 24%). Guideline and recommendation quality varied widely. Twenty (71%) guidelines incorporated at least one concept relating to antimicrobial stewardship. Including infectious diseases expertise on the guideline panel (OR 9.44, 97.5% CI: 1.09-81.59) and AGREE-REX score (OR 3.26, 97.5% CI: 1.14-9.31 per 10% increase in overall score) were associated with a higher odds of guidelines addressing antimicrobial stewardship. Interpretation: There is an opportunity to improve antibiotic prescribing guidelines in terms of both quality and incorporation of antimicrobial stewardship principles. These findings can help guideline developers better address antibiotic stewardship in future recommendations beyond COVID-19. Funding: This project was funded by Michael G. DeGroote Cochrane Canada and McMaster GRADE centres.

Swish and gargle saliva sampling is a patient-friendly and comparable alternative to nasopharyngeal swabs to detect SARS-CoV-2 in outpatient settings for adults and children.

IMPORTANCE: Widespread and frequent testing for COVID-19 was an important strategy to identify infected patients to isolate and control the spread of the disease during the pandemic. The nasopharyngeal swab (NPS) global supply chain and access to trained healthcare professionals for standard NPS collection were often compromised. Patient discomfort and limited access challenged health systems to reach large numbers for testing in adult and pediatric populations. Our study revealed that swish and gargle saliva (SGS) was comparable to NPS in detecting SARS-CoV-2 and more patient-friendly than NPS. Patients were more likely to repeat the test with SGS. SGS was amenable to self-collection instead of relying on skilled professionals. This comprehensive evaluation highlights the challenges of comparing the accuracy of new methods to imperfect gold standards and identifies additional patient-centric factors that should be considered when defining such standards. Thus, SGS is an advantageous alternative specimen collection for outpatient en masse testing.

Antibiotic Selection and Duration for Catheter-Associated Urinary Tract Infection in Non-Hospitalized Older Adults: A Population-Based Cohort Study.

Background: We sought to evaluate the impact of antibiotic selection and duration of therapy on treatment failure in older adults with catheter-associated urinary tract infection (CA-UTI). Methods: We conducted a population-based cohort study comparing antibiotic treatment options and duration of therapy for non-hospitalized adults aged 66 and older with presumed CA-UTI (defined as an antibiotic prescription and an organism identified in urine culture in a patient with urinary catheterization documented within the prior 90 d). The primary outcome was treatment failure, a composite of repeat urinary antibiotic prescribing, positive blood culture with the same organism, all-cause hospitalization or mortality, within 60 days. We determined the risk of treatment failure accounting for age, sex, comorbidities, and healthcare exposure using log-binomial regression. Results: Of 4,436 CA-UTI patients, 2,709 (61.1%) experienced treatment failure. Compared to a reference of TMP-SMX (61.9% failure), of those treated with fluoroquinolones, 56.3% experienced failure (RR 0.91, 95% CI: 0.85-0.98) and 60.9% of patients treated with nitrofurantoin experienced failure (RR 1.02, 95% CI: 0.94-1.10). Compared to 5-7 days of therapy (treatment failure: 59.4%), 1-4 days was associated with 69.5% failure (RR 1.15, 95% CI: 1.05-1.27), and 8-14 days was associated with a 62.0% failure (RR 1.05, 95% CI: 0.99-1.11). Conclusions: Although most treatment options for CA-UTI have a similar risk of treatment failure, fluoroquinolones, and treatment durations ≥ 5 days in duration appear to be associated with modestly improved clinical outcomes. From a duration of therapy perspective, this study provides reassurance that relatively short courses of 5-7 days may be reasonable for CA-UTI.

The impact of expanded access to direct acting antivirals for Hepatitis C virus on patient outcomes in Canada.

BACKGROUND: Hepatitis C virus (HCV) has high global prevalence and can lead to liver complications and death. Access to direct-acting antivirals (DAAs) in Canada increased following several policy changes, however the real-world impact of expanded DAA access and increased use of these drugs is unknown. OBJECTIVE: We aimed to determine the early change in rates of HCV-related hospitalizations overall and HCV-related hospitalizations with hepatocellular carcinoma (HCC) after expanded DAA access. METHODS: We conducted a population-based time series analysis using national administrative health databases in Canada. Rates of HCV-related hospitalizations and HCV-related hospitalizations with HCC were enumerated monthly between April 2006 and March 2020. We used Autoregressive Integrated Moving Average (ARIMA) models with ramp functions in October 2014 and January 2017 to evaluate the impact of policies to expand DAA access on hospitalization outcomes. RESULTS: Rates of HCV-related hospitalizations in Canada increased between 2006 and 2014, and gradually declined thereafter. The decrease after October 2014, or the first policy change, was significant (p = 0.0355), but no further change was found after the second policy change in 2017 (p = 0.2567). HCV-related hospitalizations with HCC increased until end of 2013, followed by a plateau, before declining in 2016. No significant shifts were found after the first policy change in 2014 (p = 0.1291) nor the second policy change in 2017 (p = 0.6324). Subgroup analyses revealed that those aged 50-64 and males had observable declines in rates of HCV-related hospitalizations in the year prior to the first policy change. CONCLUSIONS: Expanding DAA access was associated with a drop in HCV-related hospitalizations in the overall Canadian population coinciding with the 2014 policy change. In light of the time required for HCV-related complications to manifest, continued ongoing research examining the real-world effectiveness of DAAs is required.