Single-Dose Messenger RNA Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 in Healthcare Workers Extending 16 Weeks Postvaccination: A Test-Negative Design From Québec, Canada.

BACKGROUND: In Canada, first and second doses of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were uniquely spaced 16 weeks apart. We estimated 1- and 2-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Québec, Canada, including protection against varying outcome severity, variants of concern (VOCs), and the stability of single-dose protection up to 16 weeks postvaccination. METHODS: A test-negative design compared vaccination among SARS-CoV-2 test-positive and weekly matched (10:1), randomly sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by 1 dose ≥14 days or 2 doses ≥7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. RESULTS: Primary analysis included 5316 cases and 53 160 controls. Single-dose VE was 70% (95% confidence interval [CI], 68%-73%) against SARS-CoV-2 infection; 73% (95% CI, 71%-75%) against illness; and 97% (95% CI, 92%-99%) against hospitalization. Two-dose VE was 86% (95% CI, 81%-90%) and 93% (95% CI, 89%-95%), respectively, with no hospitalizations. VE was higher for non-VOCs than VOCs (73% Alpha) among single-dose recipients but not 2-dose recipients. Across 16 weeks, no decline in single-dose VE was observed, with appropriate stratification based upon prioritized vaccination determined by higher vs lower likelihood of direct patient contact. CONCLUSIONS: One mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least 4 months postvaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy.

Two-Dose Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Effectiveness With Mixed Schedules and Extended Dosing Intervals: Test-Negative Design Studies From British Columbia and Quebec, Canada.

BACKGROUND: The Canadian coronavirus disease 2019 (COVID-19) immunization strategy deferred second doses and allowed mixed schedules. We compared 2-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in 2 of Canada's larger provinces. METHODS: Two-dose VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hospitalization among adults ≥18 years, including due to Alpha, Gamma, and Delta variants of concern (VOCs), was assessed ≥14 days postvaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada, between 30 May and 27 November (epi-weeks 22-47) 2021. RESULTS: In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 2-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for ≥7 months. With slight decline from a peak of >90%, VE against infection was ≥80% for ≥6 months following homologous mRNA vaccination, lower by ∼10% when both doses were ChAdOx1 but comparably high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex, and VOC. VE was significantly higher with longer 7-8-week versus manufacturer-specified 3-4-week intervals between mRNA doses. CONCLUSIONS: Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7-8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.

Opposite action of R2R3-MYBs from different subgroups on key genes of the shikimate and monolignol pathways in spruce.

Redundancy and competition between R2R3-MYB activators and repressors on common target genes has been proposed as a fine-tuning mechanism for the regulation of plant secondary metabolism. This hypothesis was tested in white spruce [Picea glauca (Moench) Voss] by investigating the effects of R2R3-MYBs from different subgroups on common targets from distinct metabolic pathways. Comparative analysis of transcript profiling data in spruces overexpressing R2R3-MYBs from loblolly pine (Pinus taeda L.), PtMYB1, PtMYB8, and PtMYB14, defined a set of common genes that display opposite regulation effects. The relationship between the closest MYB homologues and 33 putative target genes was explored by quantitative PCR expression profiling in wild-type P. glauca plants during the diurnal cycle. Significant Spearman's correlation estimates were consistent with the proposed opposite effect of different R2R3-MYBs on several putative target genes in a time-related and tissue-preferential manner. Expression of sequences coding for 4CL, DHS2, COMT1, SHM4, and a lipase thio/esterase positively correlated with that of PgMYB1 and PgMYB8, but negatively with that of PgMYB14 and PgMYB15. Complementary electrophoretic mobility shift assay (EMSA) and transactivation assay provided experimental evidence that these different R2R3-MYBs are able to bind similar AC cis-elements in the promoter region of Pg4CL and PgDHS2 genes but have opposite effects on their expression. Competitive binding EMSA experiments showed that PgMYB8 competes more strongly than PgMYB15 for the AC-I MYB binding site in the Pg4CL promoter. Together, the results bring a new perspective to the action of R2R3-MYB proteins in the regulation of distinct but interconnecting metabolism pathways.

Neighborhood-level vaccine impact on COVID-19 infection and hospital admission in Quebec, Canada, during the Delta and early Omicron periods.

OBJECTIVE: To assess the impact of COVID-19 vaccination on COVID-19 infection and hospitalisation at the population-level, and to assess the indirect effects of vaccination in the province of Quebec, Canada. METHODS: We performed a time-stratified, neighborhood-level ecologic study. The exposure was neighborhood-level vaccination (primary series) coverage; outcomes were COVID-19 infection and hospitalisation rates. We used robust Poisson regression to estimate weekly relative rates of infection and hospitalisation versus vaccination. RESULTS: Higher vaccination coverage was associated with lower COVID-19 infection rates from July 18-December 4 for the year 2021 (Delta period) (RR≈0.46 [0.39; 0.54] - 0.94 [0.83; 1.05], 85-100% vs. 60-74% coverage). From December 5-December 25, this association reversed (RR≈1.28 [1.16; 1.41] - 1.41 [1.31; 1.52]), possibly due to the Omicron variant, social behaviors and accumulation of susceptibles in more vaccinated neighborhoods. Vaccine impact against hospitalisation was maintained throughout (RR≈0.43 [0.29; 0.65] - 0.88 [0.64; 1.22]). Vaccination provided substantial indirect protection (RR≈0.43 [0.34; 0.54] - 0.81 [0.65; 1.03]). CONCLUSIONS: This study confirmed the protective impact of vaccination against severe disease regardless of variant, at the population level. Ecological analyses are a valuable strategy to evaluate vaccination programs. Population-level effects can have substantial effects and should be accounted for in public health and vaccination program planning.

Evolution of illness severity in hospital admissions due to COVID-19, Québec, Canada, January to April 2022.

Background: The coronavirus disease 2019 (COVID-19) severity is influenced by multiple factors, such as age, underlying medical conditions, individual immunity, infecting variant, and clinical practice. The highly transmissible Omicron variants resulted in decreased COVID-19 screening capacity, which limited disease severity surveillance. Objective: To report on the temporal evolution of disease severity among patients admitted to Québec hospitals due to COVID-19 between January 2, 2022, and April 23, 2022, which corresponded to the peak period of hospitalizations due to Omicron. Methods: Retrospective population-based cohort study of all hospital admissions due to COVID-19 in Québec, between January 2, 2022, and April 23, 2022. Study period was divided into four-week periods, corresponding roughly to January, February, March and April. Regression using Cox and Poisson generalized estimating equations (GEEs) was used to quantify temporal variations in length of stay and risk of complications (intensive care admission or in-hospital death) through time, using the Omicron peak (January 2022) as reference. Measures were adjusted for age, sex, vaccination status, presence of chronic diseases, and clustering by hospital. Results: During the study period, 9,178 of all 18,272 (50.2%) patients hospitalized with a COVID-19 diagnosis were admitted due to COVID-19. Of these, 1,026 (11.2%) were admitted to intensive care and 1,523 (16.6%) died. Compared to January, the risk of intensive care admission was 25% and 31% lower in March and April respectively, while in-hospital fatality continuously decreased by 45% lower in April. The average length of stay was temporarily lower in March (9%). Conclusion: Severity of admissions due to COVID-19 decreased in the first months of 2022, when predominant circulating variants were considered to be of similar severity. Monitoring hospital admissions due to COVID-19 can contribute to disease severity surveillance.

A survey of preventive measures used and their impact on central line-associated bloodstream infections (CLABSI) in intensive care units (SPIN-BACC).

BACKGROUND: The Quebec central line-associated bloodstream infections (CLABSI) in intensive care units (ICUs) Surveillance Program saw a decrease in CLABSI rates in most ICUs. Given the surveillance trends observed in recent years, we aimed to determine what preventive measures have been implemented, if compliance to measures was monitored and its impact on CLABSI incidence rates. METHODS: All hospitals participating in the Quebec healthcare-associated infections surveillance program (SPIN-BACC - n = 48) received a 77-question survey about preventive measures implemented and monitored in their ICU. The questionnaire was validated for construct, content, face validity, and reliability. We used Poisson regression to measure the association between compliance monitoring to preventive measures and CLABSI rates. RESULTS: Forty-two (88%) eligible hospitals completed the survey. Two components from the maximum barrier precautions were used less optimally: cap (88%) and full sterile body drape (71%). Preventive measures reported included daily review of catheter need (79%) and evaluation of insertion site for the presence of inflammation (90%). Two hospitals rewired lines even if an infection was suspected or documented.In adult ICUs, there was a statistically significant greater decrease in CLABSI rates in ICUs that monitored compliance to preventive insertion measures, after adjusting for teaching status and the number of hospital beds (p = 0.036). CONCLUSIONS: Hospitals participating to the SPIN-BACC program follow recommendations for CLABSI prevention, but only a minority locally monitor their application. Compliance monitoring of preventive measures for catheter insertion was associated with a decrease in CLABSI incidence rates.

Impact of chronic comorbidities on hospitalization, intensive care unit admission and death among adult vaccinated and unvaccinated COVID-19 confirmed cases during the Omicron wave.

Background: Comorbidities are important risk factors of severe COVID-19 complications. Their impact during the Omicron wave among vaccinated and unvaccinated COVID-19 cases is not well documented. Purpose: The objective of this study was to estimate the association between the number of comorbidities and the risk of hospitalization, intensive care unit (ICU) admission, and death among vaccinated and unvaccinated confirmed adult COVID-19 cases during the Omicron wave. Research Design and Study sample: We performed a cohort study of COVID-19 adult cases of primo-infection occurring during the Omicron wave, from December 5, 2021 to January 9, 2022 using surveillance database of the province of Québec, Canada. The database included all laboratory-confirmed cases in the province and the related information on 21 pre-existing comorbidities, hospitalization, ICU admission, death related to COVID-19 and vaccination status. Analysis: We performed a robust Poisson regression model to estimate the impact of the number of comorbidities on each complication by vaccination status adjusted for age, sex, socioeconomic status, and living environment. Results: We observed that the risk of complication increased for each additional comorbidity in both vaccinated and unvaccinated individuals and that this risk was systematically higher among unvaccinated individuals. Compared with vaccinated individuals without comorbidities (reference group), the risks of hospitalization, ICU admission, and death were respectively: 9X (95% CI [7.77-12.01]), 13X (95% CI [8.74-18.87]), and 12X (95% CI [7.57-18.91]) higher in vaccinated individuals with ≥3 comorbidities; 22X (95% CI [19.07-25.95]), 45X (95% CI [29.06-69.67]) and 38X (95% CI [23.62-61.14]) higher in unvaccinated individuals with ≥3 comorbidities. Conclusion: Our results support the importance of promoting vaccination in all individuals, and especially those with pre-existing medical conditions, to reduce severe complications, even during the Omicron wave.

Seasonal variations in Clostridium difficile infections are associated with influenza and respiratory syncytial virus activity independently of antibiotic prescriptions: a time series analysis in Quebec, Canada.

Seasonal variations in Clostridium difficile-associated diarrhea (CDAD), with a higher incidence occurring during winter months, have been reported. Although winter epidemics of respiratory viruses may be temporally associated with an increase in CDAD morbidity, we hypothesized that this association is mainly due to increased antibiotic use for respiratory infections. The objective of this study was to evaluate the effect of the two most frequent respiratory viruses (influenza virus and respiratory syncytial virus [RSV]) and antibiotics prescribed for respiratory infections (fluoroquinolones and macrolides) on the CDAD incidence in hospitals in the province of Québec, Canada. A multivariable Box-Jenkins transfer function model was built to relate monthly CDAD incidence to the monthly percentage of positive tests for influenza virus and RSV and monthly fluoroquinolone and macrolide prescriptions over a 4-year period (January 2005 to December 2008). Analysis showed that temporal variations in CDAD incidence followed temporal variations for influenza virus (P = 0.043), RSV (P = 0.004), and macrolide prescription (P = 0.05) time series with an average delay of 1 month and fluoroquinolone prescription time series with an average delay of 2 months (P = 0.01). We conclude that influenza virus and RSV circulation is independently associated with CDAD incidence after controlling for fluoroquinolone and macrolide use. This association was observed at an aggregated level and may be indicative of other phenomena occurring during wintertime.

Vaccination coverage in children with juvenile idiopathic arthritis followed at a paediatric tertiary care centre.

OBJECTIVE: To evaluate the vaccination coverage rate of patients with JIA followed at a paediatric tertiary care centre and to determine the coverage rate for individual vaccines required as per the Quebec Immunization Protocol. METHODS: Consecutive JIA patients coming for their scheduled visit were included if they were between 2 and 18 years of age and if they had an available written immunization record. Descriptive statistics were used to evaluate the proportion of children with complete vaccination status according to the Quebec Immunization Protocol at 2.5, 10.5 years and at their last clinic visit. RESULTS: A total of 200 patients were included. Complete vaccination according to schedule was identified in only 52% of patients at 2.5 years, 68% at 10.5 years and 61% at their last clinic visit. The vaccination coverage rate for individual vaccines was good overall with the exception of low measles, mumps and rubella vaccine coverage at 2.5 years (58%). CONCLUSION: Despite overall good vaccination coverage rate for individual vaccines, only 61% of our cohort had a complete vaccination status at their last clinic visit. Measures to optimize vaccination coverage, such as catch-up vaccination, should be implemented when possible.

Evaluation of the 2018-2019 vaccine effectiveness against medically attended influenza-like illness using medical records and claims data.

BACKGROUND: Healthcare administrative databases are a rich source of information that could be leveraged to estimate real-world influenza vaccine effectiveness (VE). We aimed to evaluate the VE of standard egg-based influenza vaccines and determine if administrative healthcare data provide accurate VE estimates compared to the US CDC data. METHODS: This retrospective cohort study was conducted during the 2018-2019 influenza season. Individuals who had at least one relevant record per year between 2015 and 2019 in their electronic medical record were included. Individuals were considered protected 14 days after receiving an influenza vaccine. The outcome was the occurrence of medically attended influenza-like illness (MA-ILI) defined by clinical diagnostic codes. Adjusted odds ratios (aORs) were derived from multivariate logistic regression and adjusted VE (aVEs) were calculated using 100 × (1-aORs). RESULTS: A total of 5,066,980 individuals were included in the analysis with 1,307,702 (25.8%) considered vaccinated. Overall, the median age was 54 (IQR, 32-66) and 58.1% were female. Vaccine protection against MA-ILI was moderate in children and low in adults. All estimates were lower than VEs reported by the CDC for the 2018-2019 influenza season. Our results were robust to potential loss to follow up, but misclassification bias and residual confounding led to underestimation of the 2018-2019 aVE. When stratified by the number of primary care visits, aVE estimates and vaccination coverage increased with the number of primary care visits, reaching estimates similar to those obtained by the US CDC and US national vaccination coverage among those with ≥ 6 primary care visits, resulting in significant positive vaccine protection in frequent healthcare users. CONCLUSIONS: Moderate and low aVEs were observed during the 2018-2019 season using administrative healthcare data, which was likely due to detection and misclassification biases, correlated with healthcare seeking behaviour, leading to an underestimation of the 2018-2019 influenza VE.

Evaluation of influenza case definitions for use in real-world evidence research.

Background: Laboratory confirmation of influenza is not routinely done in practice. With the advent of big data, it is tempting to use healthcare administrative databases for influenza vaccine effectiveness studies, which often rely on clinical diagnosis codes. The objective of this article is to compare influenza incidence curves using international case definitions derived from clinical diagnostic codes with influenza surveillance data from the United States (US) Centers for Disease Control and Prevention (CDC). Methods: This case series describes influenza incidence by CDC week, defined using International Classification of Disease diagnostic codes over four influenza seasons (2015-2016 to 2018-2019) in a cohort of US individuals three years of age and older who consulted at least once per year between 2015 and 2019. Results were compared to the number of influenza-positive specimens or outpatient visits for influenza-like illness obtained from the CDC flu surveillance data. Results: The incidence curves of influenza-related medical encounters were very similar to the CDC's surveillance data for laboratory-confirmed influenza. Conversely, the number of influenza-like illness encounters was high when influenza viruses started to circulate, leading to a discrepancy with CDC-reported data. Conclusion: A specific case definition should be prioritized when data for laboratory-confirmed influenza are not available, as a broader case definition would conservatively bias influenza vaccine effectiveness toward the null.

Impact of the first vaccine dose on COVID-19 and its complications in long-term care facilities and private residences for seniors in Québec, Canada.

Background: Residents of long-term care facilities (LTCFs) and private residences for seniors (PRSs) were given priority for vaccination against coronavirus disease 2019 (COVID-19). Given the shortage of vaccine in the winter of 2021, the Comité sur l'immunisation du Québec recommended postponing the administration of second doses to ensure more rapid and widespread administration of first doses. The objective of this study was to measure the impact of first-dose vaccination on 1) the incidence of cases and complications in LTCFs and PRSs and 2) the frequency of outbreaks in LTCFs. Methods: In this ecological study, COVID-19 incidence and complications in residents of LTCFs and PRSs in Québec were compared with the general (community) population at a point in time when there was still only limited eligibility for vaccination. Results: After vaccination in LTCFs, the incidence rate of COVID-19 decreased by 92% compared with 49% in the community, and deaths decreased by 95%. By six weeks post-vaccination, almost no facility reported five or more cases per 100 beds per week. The incidence rate decreased by 91% in PRSs compared with 2% in the community. Hospitalizations and deaths in PRSs decreased by 94% and 90%, respectively. Conclusion: As a result of 1) vaccination of residents with one dose, 2) natural immunity already acquired in LTCFs and PRSs, 3) vaccination of healthcare workers and 4) other non-pharmaceutical prevention measures implemented, the circulation of the coronavirus in these settings was largely interrupted.

Chronic diseases and variations in rates of antimicrobial use in the community: a population-based analysis of linked administrative data in Quebec, Canada, 2002-2017.

BACKGROUND: Chronic diseases may increase risk of infection and complications from infections; fear of these risks may lower clinicians' tolerance threshold for the prescription of antimicrobials, thus increasing the risk of selecting resistant bacteria. We sought to describe rates of antimicrobial use in Quebec and measure the association between chronic diseases and utilization rates. METHODS: Using the Quebec Integrated Chronic Disease Surveillance System, we analyzed data of people covered by the public drug insurance plan in 2002-2017. Based on delivered prescriptions, we described trends in antimicrobial use in the population, and per category of select chronic diseases (i.e., none, respiratory, cardiovascular, diabetes, mental disorder), according to age group (0-17 yr, 18-64 yr and ≥ 65 yr). We computed ratios of extended-to-narrow-spectrum antimicrobials in 2014-2017. We used robust Poisson regression to quantify the association between chronic diseases and rates of antimicrobial use among children and adults (≥ 18 yr). RESULTS: Between 2002 and 2017, 4 231 724 prescriptions were received over 6 653 473 individual-years among children; 1 367 492 (20.6%) individual-years had at least 1 chronic disease. Among adults aged 18-64 years, 13 365 577 prescriptions were received over 24 935 592 individual-years; 9 533 493 (38.2%) individual-years had at least 1 chronic disease. Among adults 65 years or older, 11 689 365 prescriptions were received over 15 927 342 individual-years; 12 743 588 (80.0%) individual-years had least 1 chronic disease. Antimicrobial use decreased among children, remained stable among younger adults and increased among older adults. Trends were consistent across chronic disease categories in children and older adults. In 2014-2017, 19.9% of children, 39.1% of younger adults and 79.7% of older adults had at least 1 chronic disease. Claims for extended-spectrum antimicrobials were frequent in all age and chronic disease groups, relative to narrow-spectrum antimicrobials (ratios from 3.1:1 to 14.6:1). Antimicrobial use was higher among people with respiratory diseases (adults: relative rate [RR] 2.09, 95% confidence interval [CI] 2.07-2.10; children: RR 1.62, 95% CI 1.59-1.65), mental health diagnoses (adults: RR 1.48, 95% CI 1.46-1.49; children: RR 1.22, 95% 1.20-1.24), diabetes (adults: RR 1.40, 95% CI 1.28-1.41; children: RR 2.02, 95% CI 1.58-2.57) and cardiovascular diseases (adults: RR 1.31, 95% CI 1.30-1.32), compared with those with none of the studied chronic diseases. INTERPRETATION: During the study period, large proportions of antimicrobial prescriptions were for people with chronic diseases, across the age spectrum. Interventions to reduce antimicrobial use should be tailored for these populations.

Chronic diseases and compliance with provincial guidelines for outpatient antibiotic prescription in cases of otitis media and respiratory infections: a population-based study of linked data in Quebec, Canada, 2010-2017.

BACKGROUND: In Quebec, antibiotic use is higher among outpatients with chronic diseases. We sought to measure compliance with provincial guidelines for the treatment of otitis media and common respiratory infections, and to measure variations in compliance according to the presence of certain chronic diseases. METHODS: We conducted a population-based study of linked data on antibiotic dispensing covered by the public drug insurance plan between April 2010 and March 2017. We included patients who had consulted a primary care physician within 2 days before being dispensed an antibiotic for an infection targeted by provincial guidelines, including bronchitis in patients with chronic obstructive pulmonary disease, otitis media, pharyngitis, pneumonia and sinusitis. We computed proportions of prescriptions compliant with guidelines (use of recommended antibiotic for children, and use of recommended antibiotic and dosage for adults) by age group (children or adults) and chronic disease (respiratory, cardiovascular, diabetes, mental disorder or none). We measured the impact of chronic diseases on compliance using robust Poisson regression. RESULTS: We analyzed between 14 677 and 198 902 prescriptions for each infection under study. Compliance was greater than 87% among children, but was lower among children with asthma (proportion ratios between 0.97 and 1.00). In adults, the chosen antibiotic was compliant for at least 73% of prescriptions, except for pharyngitis (≤ 61%). Accounting for dosage lowered compliance to between 31% and 61%. Compliance was lower in the presence of chronic diseases (proportion ratios between 0.94 and 0.98). INTERPRETATION: It is possible that prescribing noncompliant prescriptions was sometimes appropriate, but the high frequency of noncompliance suggests room for improvement. Given that variations associated with chronic diseases were small, disease-specific guidelines for antibiotic prescriptions are likely to have a limited impact on compliance.

Detection of COVID-19 case clusters in Québec, May-October 2020.

OBJECTIVES: The Quebec Public Health Institute (INSPQ) was mandated to develop an automated tool for detecting space-time COVID-19 case clusters to assist regional public health authorities in identifying situations that require public health interventions. This article aims to describe the methodology used and to document the main outcomes achieved. METHODS: New COVID-19 cases are supplied by the "Trajectoire de santé publique" information system, geolocated to civic addresses and then aggregated by day and dissemination area. To target community-level clusters, cases identified as residents of congregate living settings are excluded from the cluster detection analysis. Detection is performed using the space-time scan statistic and Poisson statistical model, and implemented in the SaTScan software. Information on detected clusters is disseminated daily via an online interactive mapping interface. RESULTS: The number of clusters detected tracked with the number of new cases. Slightly more than 4900 statistically significant (p ≤ 0.01) space-time clusters were detected over 14 health regions from May to October 2020. The Montréal region was the most affected. CONCLUSION: Considering the objective of timely cluster detection, the use of near-real-time health surveillance data of varying quality over time and by region constitutes an acceptable compromise between timeliness and data quality. This tool serves to supplement the epidemiologic investigations carried out by regional public health authorities for purposes of COVID-19 management and prevention.

RéSUMé: OBJECTIFS: L'Institut national de santé publique du Québec (INSPQ) a reçu le mandat d'élaborer un outil de détection automatisé des agrégats spatio-temporels des cas de COVID-19 afin d'aider les régions à détecter des situations nécessitant des interventions de santé publique. Cet article vise à décrire la méthodologie utilisée et à présenter les principaux résultats obtenus. MéTHODE: Les nouveaux cas de COVID-19 proviennent du Système d'information Trajectoire de santé publique, ils sont géolocalisés à l'adresse civique, puis agrégés par jour et par aire de diffusion. Afin d'isoler la transmission communautaire, les cas identifiés comme résidents d'un milieu de vie fermé sont exclus des analyses de détection des agrégats. La méthode de détection est la statistique de balayage spatio-temporel basée sur le modèle de Poisson et implantée dans le logiciel SaTScan . Les agrégats détectés sont diffusés quotidiennement dans une interface cartographique web interactive. RéSULTATS: Le nombre d'agrégats détectés varie en fonction du nombre de nouveaux cas. Un peu plus de 4 900 agrégats spatio-temporels statistiquement significatifs (p ≤ 0,01) ont été détectés dans 14 régions sociosanitaires entre mai et octobre 2020. La région de Montréal est la plus touchée. CONCLUSION: Considérant l'objectif d'une détection d'agrégats en temps opportun, l'utilisation des données de vigie sanitaire en temps quasi réel, dont la qualité est variable dans le temps et selon les régions, constitue un compromis acceptable. Il s'agit d'un outil complémentaire aux enquêtes épidémiologiques menées par les autorités régionales de santé publique dans la gestion et la prévention des impacts populationnels de la COVID-19.

Role of high-risk antibiotic use in incidence of health-care-associated Clostridioides difficile infection in Quebec, Canada: a population-level ecological study.

BACKGROUND: The incidence of health-care-associated Clostridioides difficile infections has been declining in the Canadian province of Quebec since 2015. We examined whether changes in high-risk antibiotic use could account for this decrease, as reported in other jurisdictions. METHODS: We did a retrospective interrupted time-series analysis of 12 hospitals in the Canadian province of Quebec, representing a quarter of all health-care-associated C difficile infections in this region between April 1, 2012, and March 31, 2017. Data for high-risk antibiotic use (eg, amoxicillin-clavulanate, cephalosporins, fluoroquinolones, and clindamycin) in defined daily doses (DDDs) were extracted from local surveillance databases, and incidences of health-care-associated C difficile infections were extracted from provincial surveillance databases. We used hierarchical segmented Poisson regression to assess whether variations in rates of health-care-associated C difficile infections followed variations in antibiotic use. FINDINGS: Overall, 4455 health-care-associated C difficile infections and 6 281 960 patient-days were reported in the 12 participating hospitals, representing around a quarter of the provincial data. A 50% decrease in the annual incidence of health-care-associated C difficile infections was recorded between 2012-13 and 2016-17 (9·4 infections per 10 000 patient-days vs 4·7 infections per 10 000 patient-days), and a 67% decrease in the proportion of these infections due to the NAP1/027 strain of C difficile was seen (64% in 2013 vs 21% in 2017). In total, 1 266 960 DDDs of high-risk antibiotics were distributed during the study period. An increasing time trend was noted in high-risk antibiotic use, reaching a total of 223 DDDs per 1000 patient-days in 2016-17. An increase of one DDD per 1000 patient-days was associated with a 0·2% increase in the rate of health-care-associated C difficile infections in the following 4-week period. A significant change in incidence of health-care-associated C difficile infections persisted despite adjustment for high-risk antibiotic use, as shown by a significant residual step change (0·825, 95% CI 0·731-0·932) and change in trend (0·987, 0·980-0·994). INTERPRETATION: Changes in use of high-risk antibiotics do not entirely account for the sudden decrease in health-care-associated C difficile infections in the Canadian province of Quebec since 2015. Further studies are needed to understand factors implicated in the change in epidemiology of health-care-associated C difficile infections. FUNDING: Institut National de Santé Publique du Québec.

Chronic respiratory disease should be considered when interpreting indicators of community antimicrobial use in people over 65 years old.

OBJECTIVES: Chronic respiratory diseases (CRD) put patients at increased risk of respiratory infection and antimicrobial use, but surveillance results on community antimicrobial use are generally not adjusted for this risk factor. The objective of this study was to demonstrate the importance of accounting for CRD when interpreting indicators of community antimicrobial use in people over 65 years old, in Québec, Canada. METHODS: Retrospective cohort study of antimicrobial use according to CRD status in individuals over 65 years old covered by Québec's public drug insurance plan between 2010 and 2015. Defined daily doses per 1000 person-days (DID) were computed per antimicrobial class and were further stratified according to chronic disease group, fiscal year, gender and age group. RESULTS: Antimicrobial use was 2.3 times higher in the CRD group (29.7 DID) compared with the other chronic disease group (13.1 DID) and 3.1 times higher than in the no chronic disease group (9.6 DID). The same gradient was reflected as well in use per antimicrobial class, per age group, per gender, and in time. Antimicrobial use increased throughout the study period and was higher in older age groups and in women. CONCLUSIONS: Interpretation of results of antimicrobial use surveillance should consider the prevalence of CRD in populations. In order to identify opportunities for adapted interventions targeting inappropriate use, finer analyses are necessary.

Impact of influenza vaccination on healthcare utilization - A systematic review.

INTRODUCTION: Although a vaccine-preventable disease, influenza causes approximately 3-5 million cases of severe illness and about 290,000-650,000 deaths worldwide, which occur primarily among people 65 years and older. Nonetheless, prevention of influenza and its complications rely mainly on vaccination. We aimed to systematically evaluate influenza vaccine effectiveness at reducing healthcare utilization in older adults, defined as the reduction of outpatient visits, ILI and influenza hospitalizations, utilization of antibiotics and cardiovascular events by vaccination status during the influenza season. METHODS: We searched MEDLINE, EMBASE, CINAHL, Cochrane Library and considered any seasonal influenza vaccine, excluding the pandemic (2009-10 season) vaccine. Reviewers independently assessed data extraction and quality assessment. RESULTS: Of the 8308 citations retrieved, 22 studies were included in the systematic review. Overall, two studies (9%) were deemed at moderate risk of bias, thirteen (59%) at serious risk of bias and seven (32%) at critical risk of bias. For outpatient visits, we found modest evidence of protection by the influenza vaccine. For all-cause hospitalization outcomes, we found a wide range of results, mostly deemed at serious risk of bias. The included studies suggested that the vaccine may protect older adults against influenza hospitalizations and cardiovascular events. No article meeting our inclusion criteria explored the use of antibiotics and ILI hospitalizations. The high heterogeneity between studies hindered the aggregation of data into a meta-analysis. CONCLUSION: The variability between studies prevented us from drawing a clear conclusion on the effectiveness of the influenza vaccine on healthcare utilization in older adults. Overall, the data suggests that the vaccine may result in a reduction of healthcare utilization in the older population. Further studies of higher quality are necessary.

Changes in vascular accesses and in incidence rates of dialysis-related bloodstream infections in Québec, Canada, 2011-2017.

OBJECTIVE: Surveillance of dialysis-related bloodstream infections (DRBSIs) has been mandatory in Québec since April 2011. The aim of this study was to describe the epidemiology of DRBSIs in Québec. METHODS: Cohort study of prevalent patients undergoing chronic dialysis in the 36 facilities that participated without interruption in the provincial surveillance, between April 2011 and March 2017. Two indicators were analyzed: proportion of patient months dialyzed using a fistula (a patient month is a 28-day cycle during which an individual patient received dialysis) and incidence rate of DRBSI. Binomial and Poisson regression with generalized estimating equations were used to describe the evolution of indicators over time and to quantify the association between facilities' proportion of fistulas and their incidence rate. RESULTS: Globally, 42.6% of all patient months were dialyzed using a fistula, but there was a statistically significant decrease over time (46.2% in 2011-2012 to 39.3% in 2016-2017). Despite this decline in the use of fistulas, rates of DRBSIs have also decreased, going from 0.38 DRBSIs per 100 patient months in 2011-2012 to 0.23 DRBSIs per 100 patient months in 2016-2017. No association was found between facility use of fistulas and the rate of DRBSI. At the individual level, however, the DRBSI rate was 4.12 times higher for patients using a catheter. CONCLUSIONS: In Québec, the rate of DRBSIs has decreased over a 6-year period despite an increasing proportion of patients dialyzed by catheter.

Healthcare-associated bloodstream infection trends under a provincial surveillance program.

OBJECTIVE: BACTOT, Quebec's healthcare-associated bloodstream infection (HABSI) surveillance program has been operating since 2007. In this study, we evaluated the changes in HABSI rates across 10 years of BACTOT surveillance under a Bayesian framework. DESIGN: A retrospective, cohort study of eligible hospitals having participated in BACTOT for at least 3 years, regardless of their entry date. Multilevel Poisson regressions were fitted independently for cases of HABSI, catheter-associated bloodstream infections (CA-BSIs), non-catheter-associated primary BSIs (NCA-BSIs), and BSIs secondary to urinary tract infections (BSI-UTIs) as the outcome and log of patient days as the offset. The log of the mean Poisson rate was decomposed as the sum of a surveillance year effect, period effect, and hospital effect. The main estimate of interest was the cohort-level rate in years 2-10 of surveillance relative to year 1. RESULTS: Overall, 17,479 cases and 33,029,870 patient days were recorded for the cohort of 77 hospitals. The pooled 10-year HABSI rate was 5.20 per 10,000 patient days (95% CI, 5.12-5.28). For HABSI, CA-BSI, and BSI-UTI, there was no difference between the estimated posterior rates of years 2-10 compared to year 1. The posterior means of the NCA-BSI rate ratios increased from the seventh year until the tenth year, when the rate was 29% (95% confidence interval, 1%-89%) higher than the first year rate. CONCLUSIONS: HABSI rates and those of the most frequent subtypes remained stable over the surveillance period. To achieve reductions in incidence, we recommend that more effort be expended in active interventions against HABSI alongside surveillance.