Endometriosis and mental health: a population-based cohort study.

BACKGROUND: Endometriosis is a chronic gynecologic disorder that leads to considerable pain and a reduced quality of life. Although its physiological manifestations have been explored, its impact on mental health is less well defined. Existing studies of endometriosis and mental health were conducted within diverse healthcare landscapes with varying access to care and with a primary focus on surgically diagnosed endometriosis. A single-payer healthcare system offers a unique environment to investigate this association with fewer barriers to access care while considering the mode of endometriosis diagnosis. OBJECTIVE: Our objective was to assess the association between endometriosis and the risk for mental health conditions and to evaluate differences between patients diagnosed medically and those diagnosed surgically. STUDY DESIGN: A matched, population-based retrospective cohort study was conducted in Ontario and included patients aged 18 to 50 years with a first-time endometriosis diagnosis between January 1, 2010, and July 1, 2020. Endometriosis exposure was determined through either medical or surgical diagnostic criteria. A medical diagnosis was defined by the use of the corresponding International Classification of Disease diagnostic codes from outpatient and in-hospital visits, whereas a surgical diagnosis was identified through inpatient or same-day surgeries. Individuals with endometriosis were matched 1:2 on age, sex, and geography to unexposed individuals without a history of endometriosis. The primary outcome was the first occurrence of any mental health condition after an endometriosis diagnosis. Individuals with a mental health diagnosis in the 2 years before study entry were excluded. Cox regression models were used to generate hazard ratios with adjustment for hysterectomy, salpingo-oophorectomy, infertility, pregnancy history, qualifying surgery for study inclusion, immigration status, history of asthma, abnormal uterine bleeding, diabetes, fibroids, hypertension, irritable bowel disorder, migraines, and nulliparity. RESULTS: A total of 107,832 individuals were included, 35,944 with a diagnosis of endometriosis (29.5% medically diagnosed, 60.5% surgically diagnosed, and 10.0% medically diagnosed with surgical confirmation) and 71,888 unexposed individuals. Over the study period, the incidence rate was 105.3 mental health events per 1000 person-years in the endometriosis group and 66.5 mental health events per 1000 person-year among unexposed individuals. Relative to the unexposed individuals, the adjusted hazard ratio for a mental health diagnosis was 1.28 (95% confidence interval, 1.24-1.33) among patients with medically diagnosed endometriosis, 1.33 (95% confidence interval, 1.16-1.52) among surgically diagnosed patients, and 1.36 (95% confidence interval, 1.2-1.6) among those diagnosed medically with subsequent surgical confirmation. The risk for receiving a mental health diagnosis was highest in the first year after an endometriosis diagnosis and declined in subsequent years. The cumulative incidence of a severe mental health condition requiring hospital visits was 7.0% among patients with endometriosis and 4.6% among unexposed individuals (hazard ratio, 1.56; 95% confidence interval, 1.53-1.59). CONCLUSION: Endometriosis, regardless of mode of diagnosis, is associated with a marginally increased risk for mental health conditions. The elevated risk, particularly evident in the years immediately following the diagnosis, underscores the need for proactive mental health screening among those newly diagnosed with endometriosis. Future research should investigate the potential benefits of mental health interventions for people with endometriosis with the aim of enhancing their overall quality of life.

Miscarriage after SARS-CoV-2 vaccination: A population-based cohort study.

OBJECTIVE: To evaluate the risk of miscarriage following SARS-CoV-2 vaccination, while accounting for the competing risk of induced abortion. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women aged 15-50 years with a confirmed pregnancy at ≤19 completed weeks' gestation. METHODS: Exposure to first SARS-CoV-2 vaccination, handled in a time-varying manner, was defined as (i) unvaccinated, (ii) remotely vaccinated >28 days before the estimated conception date or (iii) recently vaccinated ≤28 days before conception and up to 120 days after conception. MAIN OUTCOME MEASURES: The outcome was miscarriage, occurring between the estimated date of conception and up to 19 completed weeks of pregnancy. Fine-Grey hazard models, accounting for the competing risk of induced abortion, generated hazard ratios (aHR), adjusted for socio-demographic factors, comorbidities, and biweekly periods. RESULTS: Included were 246 259 pregnant women, of whom 34% received a first SARS-CoV-2 vaccination. Miscarriage occurred at a rate of 3.6 per 10 000 person-days among remotely vaccinated women and 3.2 per 10 000 person-days among those recently vaccinated, in contrast to a rate of 1.9 per 10 000 person-days among unvaccinated women, with corresponding aHR of 0.98 (95% confidence interval [CI] 0.91-1.07) and 1.00 (95% CI 0.93-1.08). CONCLUSIONS: SARS-CoV-2 vaccination was not associated with miscarriage while accounting for the competing risk of induced abortion. This study reiterates the importance of including pregnant women in new vaccine clinical trials and registries, and the rapid dissemination of vaccine safety data.

Polycystic Ovary Syndrome, Gestational Diabetes Mellitus, and the Mediating Role of Obesity: A Population-Based Cohort Study.

This population-based cohort study in Ontario, Canada evaluated the association between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus, and the mediating effect of obesity. The study included 1 268 901 pregnancies between 2006 and 2018; 387 748 with maternal PCOS and 881 153 without PCOS. Modified Poisson regression generated relative risks adjusted for maternal covariates. Causal mediation analyses accounted for the indirect effect of obesity. Relative to individuals without PCOS, those with PCOS had a slightly higher rate (6.0% vs. 4.9%) and adjusted relative risk (1.05; 95% CI 1.03-1.06) of gestational diabetes mellitus. Obesity mediated a significant proportion (90%) of this association. Preconception counselling and future research should include strategies to support weight optimization in patients with PCOS.

Accuracy of Serum Human Chorionic Gonadotrophin for Estimating Gestational Age in the First Trimester of Pregnancy: Population-Based Study.

This study determined the accuracy of first-trimester serum human chorionic gonadotrophin (hCG) for estimating gestational age (GA). We included 273 584 singleton live births that had a first-trimester ultrasound and measured serum hCG at 4-12 weeks gestation in Ontario from 2012 to 2018. We estimated hCG accuracy compared to known GA, within a boundary of ± 1 week. Between 4 to 8 weeks gestation, sensitivity of hCG was over 88% and specificity over 51%. However, at 9-12 weeks gestation, sensitivity declined from 72% to 0%, and specificity rose from 86% to 100%. At all GA, the positive predictive value was consistently under 42%, while negative predictive values were over 96%. Within epidemiological studies in which GA is otherwise unknown, first-trimester serum hCG may aid somewhat in estimating GA between 4 to 6 weeks gestation, but much less so thereafter. Thus, there remains an ongoing need for an accurate method for estimating missing GA within large datasets.

Carotid Plaque Score is Associated with 10-year Major Adverse Cardiovascular Events in Low-Intermediate Risk Patients Referred to a General Cardiology Community Clinic.

AIMS: Atherosclerotic carotid plaque assessments have not been integrated into routine clinical practice due to the time-consuming nature of both imaging and measurements. Plaque score, Rotterdam method, is simple, quick, and only requires 4-6 B-mode ultrasound images. The aim was to assess the benefit of plaque score in a community cardiology clinic to identify patients at risk for major adverse cardiovascular events (MACE). METHODS AND RESULTS: Patients ≥40 years presenting for risk assessment were given a carotid ultrasound. Exclusions included a history of vascular disease or MACE and being >75 years. Kaplan-Meier curves and hazard ratios were performed. The left and right common carotid artery (CCA), bulb, and internal carotid artery (ICA) were given 1 point per segment if plaque present (plaque score 0 to 6). Administrative data holdings at ICES were used for 10-year event follow-up. Of 8,472 patients, 60% were females (n = 5,121). Plaque was more prevalent in males (64% vs 53.9%; P <0.0001). The 10-year MACE cumulative incidence estimate was 6.37% with 276 events (males 6.9 % vs females 6.0%; P = 0.004). Having both maximal CCA IMT <1.00 mm and plaque score = 0, was associated with less events. A plaque score <2 was associated with a low 10-year event rate (4.1%) compared to 2-4 (8.7%) and 5-6 (20%). CONCLUSION: A plaque score ≥2 can re-stratify low-intermediate risk patients to a higher risk for events. Plaque score may be used as a quick assessment in a cardiology office to guide treatment management of patients.

Renal colic imaging practice patterns in Ontario A population-based study.

INTRODUCTION: Computed tomography (CT) is associated with increased cost and exposure to radiation when compared to ultrasound (US) in patients with renal colic. Consequently, a 2014 Choosing Wisely recommendation states US should be used over CT in uncomplicated presentations in patients under age 50. The objective of this study was to describe imaging practice patterns in Ontario among patients presenting with renal colic and the relationship between initial imaging modality, subsequent imaging, and burden of care indicators. METHODS: This is a population-based study of patients who presented with renal colic in Ontario from 2003-2019 using administrative data. Patients were assessed according to their first imaging modality during their index visit. Descriptive statistics and Chi-squared test were used to examine differences between these groups. The primary outcome was the need for subsequent imaging. Secondary outcomes were length of renal colic episode, days to surgery, and number of emergency department (ED ) and primary care visits during the renal colic episode. Univariate and multivariable logistic regression models were used. RESULTS: A total of 429 060 patients were included in the final analysis. Of those, 50.5% (216 747) had CT as their initial imaging modality, 20% (84 672) had US, and 3% (13 643) had both on the same day. Subsequent imaging was obtained in 40.7% of those who had CT as the initial imaging, compared to 43% in those who had US and 43% who had both. Of those who initially had an US, 38% went on to have at least one CT during their renal colic episode, including those who had CT on the same day as initial US, while 62% were able to avoid CT altogether. In contrast, 17% had a repeat CT after an initial CT at the time of presentation. The overall use of US increased from 15% to 31% during the study period. The length of the renal colic episode was slightly longer in those who had a CT first compared to US in multivariable models (adjusted risk ratio [ARR ] 1.005, 95% confidence interval [CI] 1.000-1.009); however, the time to surgery was less in those who had a CT first (ARR 0.831, 95% CI 0.807-0.856). Fewer ED and family physician visits were seen in those who had an initial CT. CONCLUSIONS: In patients with renal colic in Ontario, approximately half have CT as the initial imaging modality despite US being recommended in uncomplicated presentations. While US use remains low, its use doubled during this study period, demonstrating an encouraging trend. Those who have US first can often avoid subsequent CT.

Physician Characteristics Associated With Opioid Prescribing After Same-Day Breast Surgery in Ontario, Canada: A Population-Based Cohort Study.

Background and Objectives: Opioid overprescribing in patients undergoing breast surgery is a concern, as evidence suggests that minimal or no opioid is needed to manage pain. We sought to describe characteristics of opioid prescribers and determine associations between prescriber's characteristics and high opioid prescribing within 7 days of same-day breast surgery. Methods: Patients ≥18 years of age who underwent same-day breast surgery in Ontario, Canada from 2012 to 2020 were identified and linked to prescriber data. The primary outcome was current high opioid prescribing defined as >75th percentile of the mean oral morphine equivalents (OME; milligrams). Prescriber characteristics including age, sex, specialty, years in practice, practice setting, and history of high (>75th percentile) opioid prescribing in the previous year were captured. Associations between prescriber characteristics and the primary outcome were estimated in modified Poisson regression models. Results: The final cohort contained 56,434 patients, 3469 unique prescribers, and 58,656 prescriptions. Over half (1971/3469; 57%) of prescribers wrote ≥1 prescription that was >75th percentile of mean OME of 180 mg, of which 50% were family practice physicians. Adjusted mean OMEs prescribed varied by specialty with family practice specialties prescribing the highest mean OME (614 ± 38 mg) compared to surgical specialties (general surgery [165 ± 9 mg], plastic surgery [198 ± 10 mg], surgical oncology [154 ± 14 mg]). Whereas 73% of first and 31% of second prescriptions were provided by general surgery physicians, family practice physicians provided 2% of first and 51% of second prescriptions. Prescriber characteristics associated with a higher likelihood of high current opioid prescribing were family practice (risk ratio [RR], 1.56; 95% confidence interval [CI], 1.35-1.79 compared to general surgery), larger community practice setting (RR, 1.34; 95% CI, 1.05-1.71 compared to urban), and a previous high opioid prescribing behavior (RR, 2.28; 95% CI, 2.06-2.52). Conclusions: While most studies examine surgeon opioid prescribing, our data suggest that other specialties contribute to opioid overprescribing in surgical patients and identify characteristics of physicians likely to overprescribe.

Variation in opioid filling after same-day breast surgery in Ontario, Canada: a population-based cohort study.

BACKGROUND: Postoperative pain management practices in breast surgery are variable, with recent evidence that approaches for minimizing or sparing opioids can be successfully implemented. We describe opioid filling and predictors of higher doses in patients undergoing same-day breast surgery in Ontario, Canada. METHODS: In this retrospective population-based cohort study, we used linked administrative health data to identify patients aged 18 years or older who underwent same-day breast surgery from 2012 to 2020. We categorized procedure types by increasing invasiveness of surgery: partial, with or without axillary intervention (P ± axilla); total, with or without axillary intervention (T ± axilla); radical, with or without axillary intervention (R ± axilla); and bilateral. The primary outcome was filling an opioid prescription within 7 or fewer days after surgery. Secondary outcomes were total oral morphine equivalents (OMEs) filled (mg, median and interquartile range [IQR]) and filling more than 1 prescription within 7 or fewer days after surgery. We estimated associations (adjusted risk ratios [RRs] and 95% confidence intervals [CIs]) between study variables and outcomes in multivariable models. We used a random intercept for each unique prescriber to account for provider-level clustering. RESULTS: Of the 84 369 patients who underwent same-day breast surgery, 72% (n = 60 620) filled an opioid prescription. Median OMEs filled increased with invasiveness (P ± axilla = 135 [IQR 90-180] mg; T ± axilla = 135 [IQR 100-200] mg; R ± axilla = 150 [IQR 113-225] mg, bilateral surgery = 150 [IQR 113-225] mg; p < 0.0001). Factors associated with filling more than 1 opioid prescription were age 30-59 years (v. age 18-29 yr), increased invasiveness (RR 1.98, 95% CI 1.70-2.30 bilateral v. P ± axilla), Charlson Comorbidity Index ≥ 2 versus 0-1 (RR 1.50, 95% CI 1.34-1.69) and malignancy (RR 1.39, 95% CI 1.26-1.53). INTERPRETATION: Most patients undergoing same-day breast surgery fill an opioid prescription within 7 days. Efforts are needed to identify patient groups where opioids may be successfully minimized or eliminated.

Endometriosis and cardiovascular disease: a population-based cohort study.

BACKGROUND: Endometriosis, a prevalent condition among females of reproductive age, may be associated with increased risk of cardiovascular disease (CVD) through chronic inflammation and early menopause. The objective of this study was to estimate the association between endometriosis and subsequent risk of CVD. METHODS: We conducted a population-based cohort study using administrative health data from Ontario residents from 1993 to 2015. We compared the incidence of CVD and cardiovascular health outcomes between females with endometriosis and 2 age-matched females without endometriosis. The primary outcome was hospital admission for CVD. Secondary outcomes included in-hospital CVD events of interest and emergency department visits for CVD. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) between endometriosis and CVD events. RESULTS: We identified 166 835 eligible patients with endometriosis and matched 333 706 patients without endometriosis. The mean age of those with endometriosis was 36.4 years. Patients with endometriosis had a higher incidence of hospital admission for CVD (195 admissions/100 000 person-years) compared with those without endometriosis (163 admissions/100 000 person-years). Similarly, the incidence of secondary CVD events was slightly higher among patients with endometriosis (292 cases/100 000 person-years) than among those without endometriosis (224 cases/100 000 person-years). Females with endometriosis had an increased risk of hospital admission (adjusted HR 1.14, 95% confidence interval [CI] 1.10-1.19) and secondary CVD events (adjusted HR 1.26, 95% CI 1.23-1.30). INTERPRETATION: In this large, population-based study, endometriosis was associated with a small increased risk of CVD events. Future studies need to investigate potential etiological mechanisms and strategies to decrease long-term CVD risk in patients with endometriosis.

Infertility and Risk of Autism Spectrum Disorder in Children.

Importance: Previous studies on the risk of childhood autism spectrum disorder (ASD) following fertility treatment did not account for the infertility itself or the mediating effect of obstetrical and neonatal factors. Objective: To assess the association between infertility and its treatments on the risk of ASD and the mediating effect of selected adverse pregnancy outcomes on that association. Design, Setting, and Participants: This was a population-based cohort study in Ontario, Canada. Participants were all singleton and multifetal live births at 24 or more weeks' gestation from 2006 to 2018. Data were analyzed from October 2022 to October 2023. Exposures: The exposure was mode of conception, namely, (1) unassisted conception, (2) infertility without fertility treatment (ie, subfertility), (3) ovulation induction (OI) or intrauterine insemination (IUI), or (4) in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Main Outcome and Measures: The study outcome was a diagnosis of ASD at age 18 months or older. Cox regression models generated hazard ratios (HR) adjusted for maternal and infant characteristics. Mediation analysis further accounted for the separate effect of (1) preeclampsia, (2) cesarean birth, (3) multifetal pregnancy, (4) preterm birth at less than 37 weeks, and (5) severe neonatal morbidity. Results: A total of 1 370 152 children (703 407 male [51.3%]) were included: 1 185 024 (86.5%) with unassisted conception, 141 180 (10.3%) with parental subfertility, 20 429 (1.5%) following OI or IUI, and 23 519 (1.7%) following IVF or ICSI. Individuals with subfertility or fertility treatment were older and resided in higher-income areas; the mean (SD) age of each group was as follows: 30.1 (5.2) years in the unassisted conception group, 33.3 (4.7) years in the subfertility group, 33.1 (4.4) years in the OI or IUI group, and 35.8 (4.9) years in the IVF or ICSI group. The incidence rate of ASD was 1.93 per 1000 person-years among children in the unassisted conception group. Relative to the latter, the adjusted HR for ASD was 1.20 (95% CI, 1.15-1.25) in the subfertility group, 1.21 (95% CI, 1.09-1.34) following OI or IUI, and 1.16 (95% CI, 1.04-1.28) after IVF or ICSI. Obstetrical and neonatal factors appeared to mediate a sizeable proportion of the aforementioned association between mode of conception and ASD risk. For example, following IVF or ICSI, the proportion mediated by cesarean birth was 29%, multifetal pregnancy was 78%, preterm birth was 50%, and severe neonatal morbidity was 25%. Conclusions and Relevance: In this cohort study, a slightly higher risk of ASD was observed in children born to individuals with infertility, which appears partly mediated by certain obstetrical and neonatal factors. To optimize child neurodevelopment, strategies should further explore these other factors in individuals with infertility, even among those not receiving fertility treatment.

Cancer incidence among Canadian Veterans: A matched cohort study.

INTRODUCTION: Occupational exposures related to military service may increase the risk of cancer for military Veterans, while high levels of fitness during service may decrease risk. However, few studies have compared this post-career cancer risk directly to the employed general population. METHODS: This retrospective cohort study used linked administrative data. Canadian Armed Forces and Royal Canadian Mounted Police Veterans in Ontario, Canada were matched 1:4 on age, sex, geography, and community-level income to a group of non-Veterans most likely to have been employed during a period similar to the Veterans' military service. Cancer diagnoses were identified using the Ontario Cancer Registry. RESULTS: During the study period, 642 of 30 576 included Veterans (2.1%) and 3408 of the 122 293 matched general population cohort (2.8%) experienced at least one cancer diagnosis. The crude rate of cancer was 153.5 per 100 000 person-years among Veterans vs. 205.9 per 100 000 person-years for the general population cohort. After adjusting for rurality and matching variables, Veterans had an 27% lower risk of developing any cancer than their matched comparators [hazard ratio = 0.73 (95% CI: 0.67-0.80)]. Among specific cancer types, the risk of lung and colorectal cancer was significantly lower for Veterans relative to the general population cohort; the risk of breast and prostate cancer was similar. DISCUSSION: This study adds to the growing international evidence suggesting that risk of many cancers among Veterans is lower or similar to the general population. Further understanding of the complex relationships among occupational exposures, environmental factors, and lifestyle factors is needed.

Characterizing Regional Variability in Lung Cancer Outcomes across Ontario-A Population-Based Analysis.

Background: Lung cancer (LC) is the leading cause of cancer-related mortality. In Ontario, Canada, there are significant survival differences for patients with newly diagnosed LC across the 14 provincial regions. Methods: A population-based retrospective cohort study using ICES databases from 01/2007-12/2017 identified patients with newly diagnosed LC through the Ontario Cancer Registry and those with LC as the cause of death. Descriptive data included patient, disease, and system characteristics. The primary outcome was 5-year survival by region. Results: 178,202 patient records were identified; 101,263 met inclusion criteria. LC incidence varied by region (5.6-14.6/10,000), as did histologic subtype (adenocarcinoma: 27.3-46.1%). Five-year cancer-specific survival was impacted by age, rurality, pathologic subtype, stage at diagnosis, and income quintile. Timely care was inversely related to survival (fastest quintile: HR 3.22, p < 0.0001). Adjusted 5-year cancer-specific survival varied across regions (24.1%, HR 1.12; 34.0%, HR 0.89, p < 0.001). Conclusions: When adjusting for confounders, differences in survival by health region persisted, suggesting a complex interplay between patient, disease, and system factors. A single approach to improving patient care is likely to be ineffective across different systems. Quality improvement initiatives to improve patient outcomes require different approaches amongst health regions to address local disparities in care.