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.

Are changes in patient-reported outcomes prognostic for diffuse large B-Cell lymphoma survival? Results from the GOYA trial.

In this hypothesis-generating analysis, we examined whether longitudinal changes in patient-reported outcomes (PROs), such as symptoms, over time would be prognostic for progression-free survival (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) who were newly treated with obinutuzumab (G) in combination with CHOP (G-CHOP) or rituximab (R) with CHOP (R-CHOP), in the GOYA Phase 3 trial (NCT01287741). Our results show that from the study baseline to cycle 3 day 1, every 1-point increase (worsening) in fever symptoms was associated with a 41% higher risk of death (hazard ratio [HR], 1.41; P = 0.01). Every 1-point increase (worsening) in lumps or swelling symptoms was associated with a 27% higher risk of disease progression or death (PFS events) (HR, 1.27; P = 0.01) and a 29% higher risk of death (OS events) (HR, 1.29; P = 0.02). No significant associations were observed between survival and changes in other symptoms, such as itching. Our study suggests that changes in some PROs are related to survival in DLBCL patients.

Multisystem inflammatory syndrome in 1.2 million children: longitudinal cohort study of risk factors.

BACKGROUND: We identified patient characteristics associated with an increased risk of developing MIS-C. METHODS: We conducted a longitudinal cohort study of 1,195,327 patients aged 0-19 years between 2006 and 2021, including the first two waves of the pandemic (February 25-August 22, 2020 and August 23, 2020-March 31, 2021). Exposures included prepandemic morbidity, birth outcomes, and family history of maternal disorders. Outcomes included MIS-C, Kawasaki disease, and other Covid-19 complications during the pandemic. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between patient exposures and these outcomes using log-binomial regression models adjusted for potential confounders. RESULTS: Among 1,195,327 children, 84 developed MIS-C, 107 Kawasaki disease, and 330 other Covid-19 complications during the first year of the pandemic. Prepandemic hospitalizations for metabolic disorders (RR 11.3, 95% CI 5.61-22.6), atopic conditions (RR 3.34, 95% CI 1.60-6.97), and cancer (RR 8.11, 95% CI 1.13-58.3) were strongly associated with the risk of MIS-C, compared with no exposure. These same exposures were also associated with Kawasaki disease and other Covid-19 complications. However, birth characteristics and history of maternal morbidity were not associated with MIS-C development. CONCLUSIONS: Children with pre-existing morbidity have a considerably elevated risk of MIS-C. IMPACT: Morbidities that predispose children to multisystem inflammatory syndrome (MIS-C) are unclear. In this study, prepandemic hospitalizations for metabolic disorders, atopic conditions, and cancer were associated with an elevated risk of MIS-C. Birth characteristics and family history of maternal morbidity were not, however, associated with MIS-C. Pediatric morbidities may play a greater role in MIS-C onset than maternal or perinatal characteristics, and may help clinicians better recognize children at risk for this complication.

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.

Sex differences in adverse events following seasonal influenza vaccines: a meta-analysis of randomised controlled trials.

BACKGROUND: Despite being a vaccine-preventable disease, influenza remains a major public health threat with vaccine safety concerns reducing vaccine acceptability. Immune responses to vaccines and adverse events may differ between males and females, but most studies do not report results by sex. Using data from clinical trials, we explored sex differences in adverse events following seasonal influenza vaccines. METHODS: We obtained data for phase III randomised controlled trials identified through a systematic review and clinical trials registries, and performed a two-stage meta-analysis. Risk ratios (RR) and 95% confidence intervals (95% CI) comparing solicited reactions in females versus males were pooled using the Mantel-Haenszel method and a random-effects model. We used the ROBINS-I tool to assess risk of bias and the I2 statistic for heterogeneity. Main analysis was stratified by age: 18-64 years and ≥65 years. RESULTS: The dataset for this analysis included 34 343 adults from 18 studies (12 with individual-level data and 6 with aggregate data). There was a higher risk of injection site reactions in females compared with males for both younger and older participants, with RRs of 1.29 (95% CI 1.21 to 1.37) and 1.43 (95% CI 1.28 to 1.60), respectively. Higher risk in females was also observed for systemic reactions, with RRs of 1.25 (95% CI 1.20 to 1.31) and 1.27 (95% CI 1.20 to 1.34) for younger and older participants, respectively. We also observed elevated risks of severe reactions in females, with a higher RR in younger versus older participants for systemic reactions (RRs 2.12 and 1.48, p=0.03, I2=79.7%). RRs were not found to vary between quadrivalent and trivalent vaccines. CONCLUSION: This meta-analysis suggested a higher risk of solicited reactions following influenza vaccines for females compared with males, irrespective of age and vaccine type. Transparent communication of this risk could increase the trust in vaccines and limit vaccine hesitancy. Future studies should report results stratified by sex and explore the role of gender in the occurrence of adverse events.

Impact of Covid-19 on risk of severe maternal morbidity.

BACKGROUND: We examined the risk of severe life-threatening morbidity in pregnant patients with Covid-19 infection. METHODS: We conducted a population-based study of 162,576 pregnancies between March 2020 and March 2022 in Quebec, Canada. The main exposure was Covid-19 infection, including the severity, period of infection (antepartum, peripartum), and circulating variant (wildtype, alpha, delta, omicron). The outcome was severe maternal morbidity during pregnancy up to 42 days postpartum. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between Covid-19 infection and severe maternal morbidity using adjusted log-binomial regression models. RESULTS: Covid-19 infection was associated with twice the risk of severe maternal morbidity compared with no infection (RR 2.02, 95% CI 1.76-2.31). Risks were elevated for acute renal failure (RR 3.01, 95% CI 1.79-5.06), embolism, shock, sepsis, and disseminated intravascular coagulation (RR 1.35, 95% CI 0.95-1.93), and severe hemorrhage (RR 1.49, 95% CI 1.09-2.04). Severe antepartum (RR 13.60, 95% CI 10.72-17.26) and peripartum infections (RR 20.93, 95% CI 17.11-25.60) were strongly associated with severe maternal morbidity. Mild antepartum infections also increased the risk, but to a lesser magnitude (RR 3.43, 95% CI 2.42-4.86). Risk of severe maternal morbidity was around 3 times greater during circulation of wildtype and the alpha and delta variants, but only 1.2 times greater during omicron. CONCLUSIONS: Covid-19 infection during pregnancy increases risk of life-threatening maternal morbidity, including renal, embolic, and hemorrhagic complications. Severe Covid-19 infection with any variant in the antepartum or peripartum periods all increase the risk of severe maternal morbidity.

Real-world impact of patient-reported outcome measurement on overall survival, healthcare use and treatment discontinuation in cancer patients.

Aim: The purpose of this retrospective, population-based, observational cohort analysis was to assess whether routine patient-reported outcomes (PRO) monitoring alone has an impact on real-world overall survival (OS) and hospitalizations among individuals diagnosed with lung, breast or colorectal cancer. The importance of follow-up care in post-PRO data collection was also discussed. Patients & methods: Administrative databases covering 17 cancer centers from Alberta, Canada were queried and individuals ≥18 years old and diagnosed with lung, breast or colorectal cancer from 1 January 2016 to 31 December 2019 were included and followed until 31 December 2020. Patients were stratified by whether they received routine PRO monitoring initiated within 120 days of diagnosis and matched 1:1 with use of propensity scores based on baseline characteristics. OS was assessed from the index date to death, and the respective Kaplan-Meier curves were estimated along with hazard ratios from Cox Proportional Hazard Models. Linear and logistic regression models were used to estimate mean differences and odds ratios (OR) respectively for healthcare resource utilization events including cancer physician visits, emergency department visits and outpatient ambulatory care encounters. Results: 4800 patients were included in each matched cohort. There was no statistically significant difference between PRO monitoring and non-monitoring cohorts in OS (HR = 1.01; 95% CI: 0.93-1.09; p = 0.836) and treatment discontinuation (OR = 0.98; 95% CI: 0.85-1.12; p = 0.75). Median OS was 51.5 months for unmonitored cohort (95% CI: 47.5-NA) versus 50.6 months for monitored cohort (95% CI: 47.6-55.7). Compared with PRO-monitored patients, unmonitored patients were associated with lower hospitalization risks (OR = 1.12; 95% CI: 1.03-1.22; p = 0.01). However, PRO-monitored patients experienced significantly fewer physician visits in comparison to unmonitored patients (MD = -1.036; 95% CI: -1.288 to -0.784, p < 0.001). Conclusion: Our results show that capturing patient-reported symptoms alone reduced the number of physician visits but neither reduced hospitalizations nor improved OS in this real-world cancer population. To drive more meaningful clinical impact, PRO monitoring programs must be met with rigorous follow-up response to the identified symptoms.

Real-World Biomarker Test Utilization and Subsequent Treatment in Patients with Early-Stage Non-small Cell Lung Cancer in the United States, 2011-2021.

INTRODUCTION: Biomarker testing is increasingly crucial for patients with early-stage non-small cell lung cancer (eNSCLC). We explored biomarker test utilization and subsequent treatment in eNSCLC patients in the real-world setting. METHODS: Using COTA's oncology database, this retrospective observational study included adult patients ≥ 18 years old diagnosed with eNSCLC (disease stage 0-IIIA) between January 1, 2011 and December 31, 2021. Date of first eNSCLC diagnosis was the study index date. We reported testing rates by index year for patients who received any biomarker test within 6 months of eNSCLC diagnosis and by each molecular marker. We also evaluated treatments received among patients receiving the five most common biomarker tests. RESULTS: Among the 1031 eNSCLC patients included in the analysis, 764 (74.1%) received ≥ 1 biomarker test within 6 months of eNSCLC diagnosis. Overall, epidermal growth factor receptor (EGFR; 64%), anaplastic lymphoma kinase (ALK; 60%), programmed death receptor ligand 1 (PD-L1; 48%), ROS proto-oncogene 1 (ROS1; 46%), B-Raf proto-oncogene (40%), mesenchymal epithelial transition factor receptor (35%), Kirsten rat sarcoma viral oncogene (29%), RET proto-oncogene (22%), human epidermal growth factor receptor 2 (21%), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (20%) were the 10 most frequently tested biomarkers. The proportion of patients undergoing biomarker testing rose from 55.3% in 2011 to 88.1% in 2021. The most common testing methods were Sanger sequencing for EGFR (244, 37%), FISH (fluorescence in situ hybridization) for ALK (464, 75%) and ROS1 (357, 76%), immunohistochemical assay for PD-L1 (450, 90%), and next-generation sequencing testing for other biomarkers. Almost all the 763 patients who received the five most common biomarker tests had a test before the initiation of a systemic treatment. CONCLUSION: This study suggests a high biomarker testing rate among patients with eNSCLC in the US, with testing rates for various biomarkers increasing over the past decade, indicating a continuous trend towards the personalization of treatment decisions.

Multisystem inflammatory syndrome in adults: Comparison with other inflammatory conditions during the Covid-19 pandemic.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is an increasingly recognized complication of Covid-19. We assessed risk factors, clinical characteristics, and outcomes of patients with MIS-A compared with other inflammatory conditions. METHODS: We analyzed a cohort of patients ≥21 years hospitalized with MIS-A in Quebec, Canada between February 2020 and March 2021. We included comparison groups that share symptomatology or pathophysiology with MIS-A, including Kawasaki disease, toxic shock syndrome, and other Covid-19 complications. We examined characteristics of men and women at admission, and identified preexisting factors associated with MIS-A through odds ratios (OR) and 95% confidence intervals (CI) from adjusted logistic regression models. RESULTS: Among 22,251 patients in this study, 52 had MIS-A, 90 Kawasaki disease, 500 toxic shock syndrome, and 21,609 other Covid-19 complications. MIS-A was associated with an elevated risk of respiratory failure compared with Kawasaki disease (OR 7.22, 95% CI 1.26-41.24), toxic shock syndrome (OR 4.41, 95% CI 1.73-11.23), and other Covid-19 complications (OR 3.03, 95% CI 1.67-5.50). Patients with MIS-A had a greater risk of cardiac involvement, renal failure, and mortality. The data pointed towards sex-specific differences in presentation, with more respiratory involvement in women and cardiac involvement in men compared with patients that had other Covid-19 complications. Except for allergic disorders and cancer, prior medical risk factors were not associated with a greater likelihood of MIS-A. CONCLUSIONS: Patients with MIS-A have an elevated risk of mortality compared with other inflammatory conditions, with women having a predominance of respiratory complications and men cardiovascular complications.

Implementing a Rural Natural Experiment: A Protocol for Evaluating the Impacts of Food Coops on Food Consumption, Resident's Health and Community Vitality.

BACKGROUND: Local food environments are recognized by experts as a determinant of healthy eating. Food cooperatives (coop) can promote the accessibility to healthier foods and thus improve the health of the population, particularly in remote rural communities. OBJECTIVE: To measure the effects of implementing a food coop in a disadvantaged community with poor access to food. We have two main research questions: (1). Does the establishment of a food coop in rural areas described as food deserts have an impact on accessibility, frequency of use, food consumption, food quality, and ultimately the health of individuals? (2). Does the establishment of a food coop in rural areas described as food deserts have an impact on food security and community vitality? DESIGN: A natural experiment with a mixed pre/post method will be used. The sample is composed of households that came from geographically isolated communities (population: 215 to 885 inhabitants) which qualified as food deserts and located in rural areas of Quebec (Canada). All communities plan to open a food coop (in the years 2022-2023), and as their opening will be staggered over time, participants from communities with a new food coop (intervention) will be compared to communities awaiting the opening of their food coop (control). Data collection was carried out at three time points: (1) before; (2) 1 to 5 months after; and (3) 13 to 17 months after the opening of the coop. Questionnaires were used to measure sociodemographic variables, dietary intake, residents' health, and community vitality. Semi-structured interviews were conducted with community stakeholders. RESULTS: Few natural experiments have been conducted regarding the impact of implementing food coops. Gathering concrete data on the effectiveness and processes surrounding these interventions through natural experiments will help to quantify their impact and guide knowledge users and policymakers to make more informed decisions.

Maternal Substance Use Disorders and Accidental Drug Poisonings in Children.

INTRODUCTION: Risk factors for accidental drug poisonings in children are poorly understood, including the association with maternal substance use. This study seeks to determine whether maternal substance use disorders before birth are associated with the future risk of accidental drug poisonings in young children. METHODS: This study was a longitudinal cohort analysis of 1,032,209 children aged <5 years between 2006 and 2020 in Quebec, Canada. The main exposure included maternal substance use disorders before or during pregnancy. The outcome was hospitalization for drug poisonings before age 5 years, including opioids, cannabis, sedatives/hypnotics, stimulants, and other drugs. Adjusted Cox proportional hazards regression was used to compute hazard ratios and 95% CIs for the association of substance use disorders with child drug poisonings during 4,523,003 person-years of follow-up. Analyses were conducted in 2020. RESULTS: Hospitalization rates for drug poisoning before age 5 years were greater for children of mothers with substance use disorders versus no substance use disorder (84.8 vs 20.7 per 100,000 person-years). Maternal substance use disorders before birth were associated with 2.28 times the risk of future drug poisonings in children (95% CI=1.63, 3.20). The association was stronger for maternal opioid use disorders (hazard ratio=4.16, 95% CI=2.38, 7.27) than other drug use disorders. Associations with child poisonings were stronger between age 1 and 2 years (hazard ratio=3.26, 95% CI=2.09, 5.10) and for poisonings involving opioids, cannabis, and sedative/hypnotic drugs. CONCLUSIONS: Maternal substance use disorders before childbirth may be markers of future risk of drug poisonings in young children.

Improving smoking cessation support for Quebec's smokers: an evaluation of Quebec's telephone quitline. / Améliorer l'aide à l'arrêt du tabagisme offerte aux fumeurs québécois : évaluation de la ligne téléphonique d'aide du Québec.

INTRODUCTION: Quitlines are an important and widespread intervention that support smokers in their efforts to quit smoking and engage them into treatment services. Quebec's quitline, called "la ligne J'ARRÊTE", has been in operation since 2002. The objectives of this study were to evaluate treatment reach, provide a description of caller characteristics and to provide results on cessation outcome measures for Quebec's smoking cessation quitline. METHODS: We collected data at intake, assessing new caller volume, caller characteristics and treatment reach. We used a one-group quasi-experimental design to assess 30-day and six-month quit rates, at six-month follow-up. Intake data were collected for 1292 new quitline callers, 18 years of age and older, over a one-year period. RESULTS: Results indicated that the service reached 9 in 10 000 Quebec smokers. With respect to the total population of smokers in Quebec, the quitline reached proportionately higher numbers of smokers who were women, were 55 years of age and older and had a high school diploma or less. At follow-up, the 30-day point prevalence abstinence rate was 26.7%, while the six-month prolonged abstinence rate was 18.8%. CONCLUSION: These results indicate that the quitline contributed to helping callers quit smoking. They are in line with findings for other quitlines in Canada and the United States. However, quitline reach is comparatively limited, suggesting that additional investment in promotional efforts and research into ways of recruiting underserved populations into the service would increase public health impact.

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.

Mosquitoes Know No Borders: Surveillance of Potential Introduction of Aedes Species in Southern Québec, Canada.

Current climatic conditions limit the distribution of Aedes (Stegomyia) albopictus (Skuse, Diptera: Culicidae) in the north, but predictive climate models suggest this species could establish itself in southern Canada by 2040. A vector of chikungunya, dengue, yellow fever, Zika and West Nile viruses, the Ae. Albopictus has been detected in Windsor, Ontario since 2016. Given the potential public health implications, and knowing that Aedes spp. can easily be introduced by ground transportation, this study aimed to determine if specimens could be detected, using an adequate methodology, in southern Québec. Mosquitoes were sampled in 2016 and 2017 along the main roads connecting Canada and the U.S., using Biogent traps (Sentinel-2, Gravide Aedes traps) and ovitraps. Overall, 24 mosquito spp. were captured, excluding Ae. Albopictus, but detecting one Aedes (Stegomyia) aegypti (Skuse) specimen (laid eggs). The most frequent species among captured adults were Ochlerotatus triseriatus, Culex pipiens complex, and Ochlerotatus japonicus (31.0%, 26.0%, and 17.3%, respectively). The present study adds to the increasing number of studies reporting on the range expansions of these mosquito species, and suggests that ongoing monitoring, using multiple capture techniques targeting a wide range of species, may provide useful information to public health with respect to the growing risk of emerging mosquito-borne diseases in southern Canada.

Pediatric surgery and future risk of cocaine, opioid, cannabis, and other substance use in women: longitudinal cohort study.

BACKGROUND: Substance use is problematic in young women, particularly in pregnancy. We sought to determine whether pediatric surgery is associated with the subsequent risk of adolescent or pregnancy-related illicit drug use, including cocaine, opioids, cannabis, and other drugs. METHODS: We analyzed a cohort of 167,119 girls aged five years or less in Canada with 4,693,444 person-years of follow-up. We tracked the girls over time between 1989 and 2018. The main exposure measure was pediatric surgery before 20 years of age. The main outcome included subsequent hospitalizations for substance use disorders and substance use in pregnancy. We estimated hazard ratios and 95% confidence intervals (CI) for the association of pediatric surgery with the later risk of substance use, using Cox proportional hazards regression models adjusted for patient characteristics. RESULTS: Pediatric surgery was associated with 2.08 times the risk of future hospitalization for substance use disorders (95% CI 1.96-2.22) and 1.48 times the risk of substance use in pregnancy (95% CI 1.35-1.62), compared with no surgery. Associations were stronger for girls who had surgery under general anesthesia and were present regardless of age at first surgery or total number of surgeries. Pediatric surgery was associated with the use of cocaine, opioids, cannabis, and other illicit substances later in life. CONCLUSIONS: This study suggests that pediatric surgery may be associated with future substance use disorders in women, including substance use at pregnancy. Further study is needed to determine whether surgery may have a causal role in later drug abuse by women.

Cannabis-related Hospitalizations Among Youth in Canada Before and After Cannabis Legalization.

OBJECTIVES: We investigated trends in cannabis-related hospitalizations among youth before and after legalization of recreational cannabis in Canada on October 17, 2018. METHODS: We computed rates of cannabis-related hospitalizations and the proportion of substance-related hospitalizations involving cannabis by age and sex in the months before and after legalization in Quebec, Canada. RESULTS: In boys aged 10 to 14 years, cannabis-related hospitalization rates increased from 5.2 per 100,000 one year before legalization [95% confidence interval (CI) 2.9-9.3] to 9.5 per 100,000 after legalization (95% CI 6.2-14.6), although the increase was not statistically significant. Cannabis was reported in 39.3% of substance-related hospitalizations in boys aged 10 to 14 years before legalization, compared with 70.0% after legalization, representing a difference of 30.7% (95% CI 2.8-58.6). There was no increase in cannabis-related hospitalizations among girls or boys aged 15 to 19 years. CONCLUSIONS: This study suggests that cannabis legalization in Canada did not increase the risk of short-term cannabis-related hospitalization among girls and older boys. However, legalization may have contributed to an increase in the risk in boys under 15 years. Further data are needed to clarify trends after legalization for younger adolescents.

Effect of publicly funded assisted reproductive technology on maternal and infant outcomes: a pre- and post-comparison study.

STUDY QUESTION: Does publicly funded assisted reproductive technology result in improved maternal and infant outcomes? SUMMARY ANSWER: Publicly funded ART in Quebec was associated with reduced risks of preeclampsia, cesarean delivery, preterm birth, low birth weight and other adverse outcomes. WHAT IS KNOWN ALREADY: Publicly funded ART programs that provide free access to single embryo transfer are known to decrease the rate of multiple pregnancy, but the impact on other pregnancy outcomes is unknown. STUDY DESIGN, SIZE, DURATION: We conducted a pre- and post-comparison study of 597 416 pregnancies conceived between July 2008 and September 2015 in Quebec, Canada, a region where public funding of ART began in August 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all pregnant women who conceived by ART (n = 14 309) or spontaneously (n = 583 107) and delivered a live or stillborn infant in hospitals of Quebec. The main exposure measure was conception before versus during the publicly funded ART program. Outcomes included measures of maternal and infant morbidity and mortality. We estimated risk ratios (RR) and 95% confidence intervals for the association of publicly funded ART with maternal and infant outcomes using log-binomial regression models adjusted for maternal characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: In this study, 2638 pregnancies were conceived by ART before, and 11 671 were conceived by ART, during public funding. Compared with no public funding, ART funding was associated with reduced risks of severe maternal morbidity (RR 0.64, 95% CI 0.50-0.83), preeclampsia (RR 0.55, 95% CI 0.44-0.68), cesarean delivery (RR 0.83, 95% CI 0.77-0.89), preterm birth (RR 0.67, 95% CI 0.60-0.75), low birth weight (RR 0.63, 95% CI 0.55-0.72), severe neonatal morbidity (RR 0.75, 95% CI 0.57-0.99) and neonatal intensive care unit admission (RR 0.65, 95% CI 0.53-0.78). When multiple pregnancies were excluded, ART funding continued to be associated with a lower risk of preeclampsia (RR 0.61, 95% CI 0.48-0.79) and preterm birth (RR 0.85, 95% CI 0.73-0.99). However, ART funding was associated with increased risk of gestational diabetes. LIMITATIONS, REASONS FOR CAUTION: We had no information on the type of ART, number of in-vitro fertilization cycles or number of embryos transferred. We lacked data on body mass index, ethnicity and smoking and cannot rule out residual confounding. WIDER IMPLICATION OF THE FINDINGS: Our findings suggest that publicly funded ART programs that encourage single embryo transfer may have substantial benefits for a range of maternal and infant outcomes, beyond prevention of multiple births. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grant 6D02363004 from the Public Health Agency of Canada. N.A. acknowledges a career award from the Fonds de recherche du Québec-Santé (34695). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Maternal Mental Disorders before Delivery and the Risk of Dental Caries in Children.

Prevention of childhood caries is an ongoing public health challenge, but the possibility of an association with maternal mental disorders has received limited attention. We estimated the extent to which maternal mental disorders are associated with an increased risk of hospitalization due to dental caries. We conducted a longitudinal cohort study of 790,758 infants born in Quebec, Canada between 2006 and 2016, with follow-up extending to 2018. We identified women with mental disorders before or during pregnancy and computed the incidence of dental caries in their children. We estimated HR and 95% CI for the association of maternal mental disorders with the risk of dental caries, adjusted for personal characteristics. Infants of women with mental disorders before or during pregnancy had a higher incidence of dental caries compared to children of women with no mental disorder (56.1 vs. 27.2 per 10,000 person-years). Maternal stress and anxiety disorders (HR = 1.73; 95% CI 1.60-1.86), depression (HR = 1.81; 95% CI 1.60-2.03), schizophrenia and delusional disorders (HR = 1.69; 95% CI 1.29-2.22), and personality disorders (HR = 1.89; 95% CI 1.70-2.11) were associated with the risk of dental caries. The associations were present throughout childhood, including after 7 years (HR = 1.65; 95% CI 1.38-1.96). Maternal mental disorders were associated with caries of the enamel, dentin, and cementum and caries that reached the dental pulp. Maternal mental disorders before or during pregnancy, especially stress and anxiety, depression, schizophrenia, and personality disorders, are associated with the risk of childhood caries. Women with a history of mental disorders may benefit from enhanced strategies for prevention of dental caries in their children.