Association between opioid use disorder and palliative care: a cohort study using linked health administrative data in Ontario, Canada.

BACKGROUND: People with opioid use disorder (OUD) are at risk of premature death and can benefit from palliative care. We sought to compare palliative care provision for decedents with and without OUD. METHODS: We conducted a cohort study using health administrative databases in Ontario, Canada, to identify people who died between July 1, 2015, and Dec. 31, 2021. The exposure was OUD, defined as having emergency department visits, hospital admissions, or pharmacologic treatments suggestive of OUD within 3 years of death. Our primary outcome was receipt of 1 or more palliative care services during the last 90 days before death. Secondary outcomes included setting, initiation, and intensity of palliative care. We conducted a secondary analysis excluding sudden deaths (e.g., opioid toxicity, injury). RESULTS: Of 679 840 decedents, 11 200 (1.6%) had OUD. Compared with people without OUD, those with OUD died at a younger age and were more likely to live in neighbourhoods with high marginalization indices. We found people with OUD were less likely to receive palliative care at the end of their lives (adjusted relative risk [RR] 0.84, 95% confidence interval [CI] 0.82-0.86), but this difference did not exist after excluding people who died suddenly (adjusted RR 0.99, 95% CI 0.96-1.01). People with OUD were less likely to receive palliative care in clinics and their homes regardless of cause of death. INTERPRETATION: Opioid use disorder can be a chronic, life-limiting illness, and people with OUD are less likely to receive palliative care in communities during the 90 days before death. Health care providers should receive training in palliative care and addiction medicine to support people with OUD.

A Population-Based Test-Negative Matched Case-Control Analysis of SARS-CoV-2 Vaccine Effectiveness Among Pregnant People in Ontario, Canada.

OBJECTIVE: Pregnancy is a risk factor for severe SARS-CoV-2 infection, which can result in adverse pregnancy outcomes, thus making understanding vaccine effectiveness (VE) in this population important. This study aimed to assess the VE of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization in pregnant people. METHODS: Population-based matched test-negative case-control study of pregnant people aged 18-49 years, of 12 or more weeks gestation in Ontario, Canada, symptomatic with possible SARS-CoV-2 infection, and having at least 1 positive (n = 1842) or negative (n = 8524) real-time polymerase chain reaction (RT-PCR) SARS-CoV-2 test between December 14, 2020, and December 31, 2021. The exposure was receipt of ≥1 dose of mRNA COVID-19 vaccine versus no vaccination. Exposure was further stratified by number and recency of doses. The primary outcome was a positive SARS-CoV-2 RT-PCR test. As a secondary outcome, VE for COVID-19-related hospitalization was assessed. RESULTS: In the primary outcome analysis, there were 1821 positive cases, matched to 1821 negative controls. The mean (SD) maternal age was 31 (5) years. When compared to those unvaccinated, receipt of ≥1 dose was associated with an estimated VE of 39% (95% CI 29%-48%) for symptomatic infection, and 85% (95% CI 72%-92%) for COVID-19 hospitalization. VE estimates demonstrated waning with increased time since last vaccination. CONCLUSIONS: mRNA COVID-19 vaccines provide protection against symptomatic COVID-19 illness and are highly effective at preventing severe illness in pregnant people. The observed effect of vaccine waning highlights the importance of booster doses to provide optimal protection for pregnant people.

The Association Between Pregnancy Timing and Cumulative Exposure on Survival in Melanoma.

BACKGROUND: As melanoma is common among young women, the impact of pregnancy on melanoma prognosis is of interest. OBJECTIVE: The purpose of this study was to examine the association between pregnancy and survival in female melanoma patients of childbearing age. METHODS: We performed a population-level, retrospective cohort study of women of childbearing age (18-45 years) diagnosed with melanoma from 2007 to 2017 using administrative data from Ontario, Canada. Patients were categorized according to pregnancy status (i.e. pregnancy before [conception from 60 to 13 months prior to melanoma], pregnancy-associated [conception 12 months prior to and after], and pregnancy after [conception 12 months after] melanoma). Cox models were used to examine melanoma-specific survival (MSS) and overall survival (OS) associated with pregnancy status. RESULTS: Of 1312 women with melanoma, most did not experience pregnancy (84.1%), with 7.6% experiencing a pregnancy-associated melanoma and 8.2% experiencing a pregnancy after melanoma. Pregnancy before melanoma occurred in 18.1% of patients. Pregnancy before (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.35-1.28), associated (HR 1.15, 95% CI 0.45-2.97), and after melanoma (HR 0.39, 95% CI 0.13-1.11) was not associated with a difference in MSS compared with those who did not experience a pregnancy during these time periods. Pregnancy status was also not associated with a difference in OS (p > 0.05). Cumulative weeks pregnant were not associated with a difference in MSS (4-week HR 0.99, 95% CI 0.92-1.07) or OS (4-week HR 1.00, 95% CI 0.94-1.06). CONCLUSIONS: In this population-level analysis of female melanoma patients of childbearing age, pregnancy was not associated with a difference in survival, suggesting that pregnancy is not associated with a worse melanoma prognosis.

Prescription of oxycodone versus codeine after childbirth and risk of persistent opioid use: a population-based cohort study.

BACKGROUND: Oxycodone is increasingly prescribed for postpartum analgesia in lieu of codeine owing to concerns regarding the neonatal safety of codeine during lactation. We examined whether initiation of oxycodone after delivery was associated with an increased risk of persistent opioid use relative to initiation of codeine. METHODS: We conducted a population-based cohort study of people who filled a prescription for either codeine or oxycodone within 7 days of discharge from hospital after delivery between Sept. 1, 2012, and June 30, 2020. The primary outcome was persistent opioid use, defined as 1 or more additional prescriptions for an opioid within 90 days of the first postpartum prescription and 1 or more additional prescriptions in the 91 to 365 days thereafter. We used inverse probability of treatment weighting to assess the risk of persistent postpartum opioid use, comparing people who initiated oxycodone with those who initiated codeine. RESULTS: Over the 8-year study period, we identified 70 607 people who filled an opioid prescription within 7 days of discharge from hospital: 21 308 (30.2%) received codeine and 49 299 (69.8%) oxycodone. Compared with people who filled a prescription for codeine, receipt of oxycodone was not associated with persistent opioid use (relative risk [RR] 1.04, 95% confidence interval [CI] 0.91-1.20). We found an association between a prescription for oxycodone and persistent use after vaginal delivery (RR 1.63, 95% CI 1.31-2.03), but not after cesarean delivery (RR 0.85, 95% CI 0.73-1.00). INTERPRETATION: Initiation of oxycodone (v. codeine) was not associated with an increased risk of persistent opioid use, except after vaginal delivery.

Ethnic disparities in COVID-19 outcomes: a multinational cohort study of 20 million individuals from England and Canada.

BACKGROUND: Heterogeneous studies have demonstrated ethnic inequalities in the risk of SARS-CoV-2 infection and adverse COVID-19 outcomes. This study evaluates the association between ethnicity and COVID-19 outcomes in two large population-based cohorts from England and Canada and investigates potential explanatory factors for ethnic patterning of severe outcomes. METHODS: We identified adults aged 18 to 99 years in the QResearch primary care (England) and Ontario (Canada) healthcare administrative population-based datasets (start of follow-up: 24th and 25th Jan 2020 in England and Canada, respectively; end of follow-up: 31st Oct and 30th Sept 2020, respectively). We harmonised the definitions and the design of two cohorts to investigate associations between ethnicity and COVID-19-related death, hospitalisation, and intensive care (ICU) admission, adjusted for confounders, and combined the estimates obtained from survival analyses. We calculated the 'percentage of excess risk mediated' by these risk factors in the QResearch cohort. RESULTS: There were 9.83 million adults in the QResearch cohort (11,597 deaths; 21,917 hospitalisations; 2932 ICU admissions) and 10.27 million adults in the Ontario cohort (951 deaths; 5132 hospitalisations; 1191 ICU admissions). Compared to the general population, pooled random-effects estimates showed that South Asian ethnicity was associated with an increased risk of COVID-19 death (hazard ratio: 1.63, 95% CI: 1.09-2.44), hospitalisation (1.53; 1.32-1.76), and ICU admission (1.67; 1.23-2.28). Associations with ethnic groups were consistent across levels of deprivation. In QResearch, sociodemographic, lifestyle, and clinical factors accounted for 42.9% (South Asian) and 39.4% (Black) of the excess risk of COVID-19 death. CONCLUSION: International population-level analyses demonstrate clear ethnic inequalities in COVID-19 risks. Policymakers should be cognisant of the increased risks in some ethnic populations and design equitable health policy as the pandemic continues.

Venous Thromboembolism in Patients Discharged From the Emergency Department With Ankle Fractures: A Population-Based Cohort Study.

STUDY OBJECTIVE: Temporary lower limb immobilization may be a risk for venous thromboembolism. The purpose of this study was to examine the 90-day incidence of venous thromboembolism among patients discharged from an emergency department (ED) with ankle fractures requiring temporary immobilization. Secondary objectives were to examine individual factors associated with venous thromboembolism in this population and to compare the risk of venous thromboembolism in patients with ankle fractures against a priori-selected control groups. METHODS: This was a retrospective cohort study using province-wide health datasets from Ontario, Canada. We included patients aged 16 years and older discharged from an ED between 2013 and 2018 with closed ankle fractures requiring temporary immobilization. We estimated 90-day incidence of venous thromboembolism after ankle fracture. A Cox proportional hazards model was used to evaluate risk factors associated with venous thromboembolism, censoring at 90 days or death. Patients with ankle fractures were then propensity score matched to 2 control groups: patients discharged with injuries not requiring lower limb immobilization (ie, finger wounds and wrist fractures) to compare relative hazard of venous thromboembolism. RESULTS: There were 86,081 eligible patients with ankle fractures. Incidence of venous thromboembolism within 90 days was 1.3%. Factors associated with venous thromboembolism were older age (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 1.00 to 1.39), venous thromboembolism or superficial venous thrombosis history (HR: 5.18; 95% CI: 4.33 to 6.20), recent hospital admission (HR: 1.33; 95% CI: 1.05 to 1.68), recent nonankle fracture surgery (HR: 1.58; 95% CI: 1.30 to 1.93), and subsequent surgery for ankle fracture (HR: 1.80; 95% CI: 1.48 to 2.20). In the matched cohort, patients with ankle fractures had an increased hazard of venous thromboembolism compared to matched controls with finger wounds (HR: 6.31; 95% CI: 5.30 to 7.52) and wrist fractures (HR: 5.68; 95% CI: 4.71 to 6.85). CONCLUSION: The 90-day incidence of venous thromboembolism among patients discharged from the ED with ankle fractures requiring immobilization was 1.3%. These patients had a 5.7- to 6.3-fold increased hazard compared to matched controls. Certain patients immobilized for ankle fractures are at higher risk of venous thromboembolism, and this should be recognized by emergency physicians.

Preeclampsia and Severe Maternal Morbidity During the COVID-19 Pandemic: A Population-Based Cohort Study in Ontario, Canada.

OBJECTIVE: Significant changes to the delivery of obstetrical care that occurred with the onset of the COVID-19 pandemic may be associated with higher risks of adverse maternal outcomes. We evaluated preeclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome and composite severe maternal morbidity (SMM) among pregnant people who gave birth during the COVID-19 pandemic and compared these data with those of people who gave birth before the pandemic in Ontario, Canada. METHODS: This was a population-based, retrospective cohort study using linked administrative data sets from ICES. Data on pregnant people at ≥20 weeks gestation who gave birth between March 15, 2020, and September 30, 2021, were compared with those of pregnant people who gave birth within the same date range for the years 2015-2019. We used multivariable logistic regression to assess the effect of the pandemic period on the odds of preeclampsia/HELLP syndrome and composite SMM, adjusting for maternal baseline characteristics and comorbidities. RESULTS: There were no differences between the study periods in the adjusted odds ratios (aORs) for preeclampsia/HELLP syndrome among primiparous (aOR 1.00; 95% CI 0.91-1.11) and multiparous (aOR 0.94; 95% CI 0.81-1.09) patients and no differences for composite SMM (primiparous, aOR 1.00; 95% CI 0.95-1.05; multiparous, aOR 1.01; 95% CI 0.95-1.08). CONCLUSION: Adverse maternal outcomes were not higher among pregnant people who gave birth during the first 18 months of the COVID-19 pandemic in Ontario, Canada, when compared with those who gave birth before the pandemic.

DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis.

Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry-specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10-5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.

Recent Improvements in Attainment of the Hemoglobin A1c Target of ≤7.0% Among Adults with Type 1 Diabetes in Ontario: A Retrospective Cohort Study.

Aims: We evaluated attainment of the hemoglobin A1c (HbA1c) target of ≤7.0%, its temporal trends, and associated factors among adults with type 1 diabetes in Ontario, Canada, using administrative data. Methods: We conducted a retrospective cohort study, including Ontarians with type 1 diabetes ≥18 years old with ≥1 HbA1c test between April 1, 2012 (fiscal year 2013), and March 31, 2023. Generalized estimating equations were used to determine probabilities of meeting the HbA1c target, as well as associations between fiscal year and individual-, physician-, and system-level factors on odds of meeting the target. Results: Among 28,827 adults with type 1 diabetes [14,385 (49.9%) female, 17,998 (62.4%) pump users], with median age at index of 25 years [interquartile range (IQR) 18-37] and median diabetes duration of 12 years [6-18], there were 474,714 HbA1c tests [median 2/individual/year (IQR: 1-3)]. The model-estimated probability of meeting the HbA1c target of ≤7.0% was 22.1% (95% confidence interval, CI: 21.6 to 22.5) in 2013, remained stable until 2020, and increased to 34.7% (95% CI: 34.3 to 35.2) in 2023. The age- and sex-adjusted odds ratio for meeting the target in 2023 versus 2013 was 1.87 (95% CI: 1.79 to 1.96). Young adults (18-25 years), diabetic ketoacidosis, greater comorbidity, and receiving diabetes care from a nonspecialist physician were associated with reduced odds of meeting the HbA1c target. Conclusions: One-third of adults with type 1 diabetes in Ontario met the recommended HbA1c target of ≤7.0% in 2023, with improvement noted since 2021, which may be due to advanced technologies or effects of the COVID-19 pandemic.

A population-based time-series analysis of opioid agonist treatment dispensed during pregnancy.

BACKGROUND AND AIMS: Identifying effective opioid treatment options during pregnancy is a high priority due to the growing prevalence of opioid use disorder across North America. We assessed the temporal impact of three population-level interventions on the use of opioid agonist treatment (OAT) during pregnancy in Ontario, Canada. DESIGN: This was a population-based time-series analysis to identify trends in the monthly prevalence of pregnant people dispensed methadone and buprenorphine. The impact of adding buprenorphine/naloxone to the public drug formulary, the release of pregnancy-specific guidance and the start of the COVID-19 pandemic were assessed. SETTING AND PARTICIPANTS: The study was conducted in Ontario, Canada between 1 July 2013 and 31 March 2022, comprising people who delivered a live or stillbirth in any Ontario hospital during the study period. MEASUREMENTS: We identified any prescription for methadone or buprenorphine dispensed between the estimated conception date and delivery date and calculated the monthly prevalence of OAT-exposed pregnancies among all pregnant people in Ontario. FINDINGS: Overall, rates of OAT during pregnancy have declined since mid-2018. Methadone-exposed pregnancies decreased from 0.46% of all pregnancies in Ontario in 2015 to a low of 0.16% in 2022. In the primary analysis, none of the interventions had a statistically significant impact on overall OAT rates; however, in the stratified analyses, there was a small increase in buprenorphine after the formulary change [0.006%, 95% confidence interval (CI) = 0.0032-0.0081, P < 0.0001] and a decrease in buprenorphine after the release of the 2017 guidelines (-0.005%, 95% CI = -0.0080 to -0.0020, P = 0.001) and the start of the COVID-19 pandemic (-0.003%, 95% CI = -0.0054 to -0.0006, P = 0.015). CONCLUSION: Despite changes in guidance and funding, opioid agonist treatment during pregnancy has been declining in Ontario, Canada since 2018.

Hepatitis C Attributable Healthcare Costs and Mortality among Immigrants: A Population-Based Matched Cohort Study.

Background: Data on the economic burden of chronic hepatitis C (CHC) among immigrants are limited. Our objective was to estimate the CHC-attributable mortality and healthcare costs among immigrants in Ontario, Canada. Methods: We conducted a population-based matched cohort study among immigrants diagnosed with CHC between May 31, 2003, and December 31, 2018, using linked health administrative data. Immigrants with CHC (exposed) were matched 1 : 1 to immigrants without CHC (unexposed) using a combination of hard (index date, sex, and age) and propensity-score matching. Net costs (2020 Canadian dollars) collected from the healthcare payer perspective were calculated using a phase-of-care approach and used to estimate long-term costs adjusted for survival. Results: We matched 5,575 exposed individuals with unexposed controls, achieving a balanced match. The mean age was 47 years, and 52% was male. On average, 10.5% of exposed and 3.5% of unexposed individuals died 15 years postindex (relative risk = 2.9; 95% confidence interval (CI): 2.6-3.5). The net 30-day costs per person were $88 (95% CI: 55 to 122) for the prediagnosis, $324 (95% CI: 291 to 356) for the initial phase, $1,016 (95% CI: 900 to 1,132) for the late phase, and $975 (95% CI: -25 to 1,974) for the terminal phase. The mean net healthcare cost adjusted for survival at 15 years was $90,448. Conclusions: Compared to unexposed immigrants, immigrants infected with CHC have higher mortality rates and greater healthcare costs. These findings will support the planning of HCV elimination efforts among key risk groups in the province.

New Persistent Opioid Use After Childbirth.

OBJECTIVE: To examine factors associated with new persistent opioid use after childbirth. METHODS: We conducted a population-based cohort study of individuals who initiated opioid therapy within 7 days of discharge from hospital after delivery between September 1, 2013, and September 30, 2021. The primary outcome was new persistent opioid use , which was defined as one or more prescriptions for an opioid within 90 days of the first postpartum prescription and one or more subsequent opioid prescriptions in the 91-365 days afterward. We used multivariable logistic regression to assess patient-, pregnancy-, and prescription-related factors associated with new persistent opioid use after delivery. RESULTS: We identified 118,694 unique deliveries after which opioids were initiated, including 99,399 cesarean (83.7%) and 19,295 vaginal (16.3%) deliveries. Among mothers who initiated an opioid after delivery, 1,282 (10.8/1,000 deliveries) met our definition of new persistent opioid use in the subsequent year. Rates of new persistent opioid use were appreciably higher after vaginal (16.0/1,000) compared with cesarean (9.8/1,000) deliveries. Each additional 30 morphine milligram equivalents in the initial opioid prescription was associated with an increased risk of new persistent use after cesarean (adjusted odds ratio [aOR] 1.06, 95% CI 1.04-1.08) and vaginal (aOR 1.05, 95% CI 1.02-1.08) delivery. A concomitant benzodiazepine prescription after cesarean delivery was associated with a markedly increased risk of persistent opioid use (aOR 2.69, 95% CI 1.60-4.52). CONCLUSION: Among people who filled an opioid prescription after delivery, about 1% displayed evidence of persistent opioid use in the subsequent year. Initial prescriptions for large quantities of opioids and a concurrent benzodiazepine prescription may be important modifiable risk factors to prevent new persistent opioid use after delivery.

Engagement with the HCV care cascade among high-risk groups: A population-based study.

BACKGROUND: HCV elimination requires a thorough understanding of the care cascade. A direct-acting antiviral (DAA)-era description of the care cascade has not been undertaken in Ontario, Canada's most populous jurisdiction. Our primary objective was to describe the current population-level care cascade in the general Ontario population and among key risk groups ─ baby boomers, immigrants, and individuals experiencing residential instability. The secondary objective was to identify predictors of engagement. METHODS: We conducted a population-based cohort study of Ontario residents undergoing HCV testing between January 1, 1999, and December 31, 2018, and mapped the care cascade [antibody-diagnosed, RNA tested, RNA positive, genotyped, treated, achieved sustained virologic response, reinfected/relapsed] as of December 31, 2018. The cascade was stratified by risk groups. Cause-specific hazard modeling was used to identify demographic, and socioeconomic predictors of engagement with key steps of the cascade. RESULTS: Among 108,428 Ontario residents living with an HCV antibody diagnosis, 88% received confirmatory RNA testing; of these, 62% tested positive and 94% of positive tests were genotyped. Of those with confirmed viremia, 53% initiated treatment and 76% of treated individuals achieved sustained virologic response, while ~1% experienced reinfection or relapse. Males, older birth cohorts, long-term residents, those with a history of substance use disorder and social marginalization (eg, material deprivation, residential instability), and those initially diagnosed in the pre-DAA era exhibited lower rates of engagement with almost every step of HCV care. CONCLUSIONS: Despite DAA era improvements, treatment initiation remains a major gap. HCV screening and linkage-to-treatment, particularly for those with a history of substance use disorder and social marginalization, will be needed to equitably close gaps in HCV care in the province.

Short- and Long-Term Outcomes in Patients With Thrombophilia Undergoing Transcatheter Closure of Patent Foramen Ovale.

BACKGROUND: Patients with thrombophilia are underrepresented in studies evaluating outcomes after closure of patent foramen ovale (PFO). Real-world data on long term outcomes in this population are very limited. OBJECTIVES: This study compared outcomes in patients with and without thrombophilia undergoing PFO closure, using data from a large, clinical database linked to population-based databases. METHODS: This retrospective cohort study included consecutive patients who had a transcatheter PFO closure and had preprocedural thrombophilia screening. Data from a retrospective, clinical registry were linked to population-based administrative databases in Ontario Canada to evaluate outcomes. Outcomes were reported as rates per 100 person-years and compared using Poisson regression. RESULTS: We included 669 patients, with a mean age of 56.4 years, 97.9% of whom underwent PFO closure for a cryptogenic stroke. Thrombophilia was diagnosed among 174 (26.0%), of which 86% had inherited mutations. In-hospital, procedural complications were observed in 3.1% of patients with no difference by thrombophilia status. Similarly, no differences were observed in 30-day emergency department visits and readmissions. Over the median follow-up of 11.6 years, the most common adverse outcome was new-onset atrial fibrillation (1.0 per 100 person-years; 95% CI: 0.8-1.2), followed by recurrent cerebrovascular events (0.8 per 100 person-years; 95% CI: 0.6-1.1) with no differences between the groups (P > 0.05). CONCLUSIONS: After PFO closure, no differences were observed in long-term adverse outcomes between patients with and without thrombophilia. Though these patients have been excluded from randomized clinical trials of PFO closure in the past, real-world evidence supports their eligibility for the procedure.

Maternal opioid treatment after delivery and risk of adverse infant outcomes: population based cohort study.

OBJECTIVE: To examine whether maternal opioid treatment after delivery is associated with an increased risk of adverse infant outcomes. DESIGN: Population based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: 865 691 mother-infant pairs discharged from hospital alive within seven days of delivery from 1 September 2012 to 31 March 2020. Each mother who filled an opioid prescription within seven days of discharge was propensity score matched to a mother who did not. MAIN OUTCOME MEASURES: The primary outcome was hospital readmission of infants for any reason within 30 days of their mother filling an opioid prescription (index date). Infant related secondary outcomes were any emergency department visit, hospital admission for all cause injury, admission to a neonatal intensive care unit, admission with resuscitation or assisted ventilation, and all cause death. RESULTS: 85 675 mothers (99.8% of the 85 852 mothers prescribed an opioid) who filled an opioid prescription within seven days of discharge after delivery were propensity score matched to 85 675 mothers who did not. Of the infants admitted to hospital within 30 days, 2962 (3.5%) were born to mothers who filled an opioid prescription compared with 3038 (3.5%) born to mothers who did not. Infants of mothers who were prescribed an opioid were no more likely to be admitted to hospital for any reason than infants of mothers who were not prescribed an opioid (hazard ratio 0.98, 95% confidence interval 0.93 to 1.03) and marginally more likely to be taken to an emergency department in the subsequent 30 days (1.04, 1.01 to 1.08), but no differences were found for any other adverse infant outcomes and there were no infant deaths. CONCLUSIONS: Findings from this study suggest no association between maternal opioid prescription after delivery and adverse infant outcomes, including death.

Effects of an academic detailing service on benzodiazepine prescribing patterns in primary care.

BACKGROUND: Benzodiazepines are commonly used to treat anxiety and/or insomnia but are associated with substantial safety risks. Changes to prescribing patterns in primary care may be facilitated through tailored quality improvement strategies. Academic detailing (AD) may be an effective method of promoting safe benzodiazepine prescribing. The objective of this study was to evaluate the effectiveness of AD on benzodiazepine prescribing among family physicians. METHODS AND FINDINGS: We used an interrupted time series matched cohort design using population-based administrative claims databases. Participants were family physicians practicing in Ontario, Canada. The intervention was a voluntary AD service which involves brief service-oriented educational outreach visits by a trained pharmacist. The focus was on key messages for safer benzodiazepine prescribing in primary care with an emphasis on judicious prescribing to older adults aged 65 and older. Physicians in the intervention group were those who received at least one AD visit on benzodiazepine use between June 2019 and February 2020. Physicians in the control group were included if they did not receive an AD visit during the study period. Intervention physicians were matched to control physicians 1:4, on a variety of characteristics. Physicians were excluded if they had inactive billing or billing of less than 100 unique patient visits in the calendar year prior to the index date. The primary outcome was mean total benzodiazepine prescriptions at the level of the physician. Secondary outcomes were rate (per 100) of patients with long-term prescriptions, high-risk prescriptions, newly started prescriptions, and benzodiazepine-related patient harms. Data were analyzed using a repeated measures pre-post comparison with an intention-to-treat. Analyses were then stratified to focus on effects within higher-prescribing physicians. There were 1337 physicians were included in the study; 237 who received AD and 1064 who did not. There was no significant change in benzodiazepine prescribing when considering all physicians in the intervention and matched control groups. Although not significant, a greater reduction in total benzodiazepine prescriptions was observed amongst the highest-volume prescribing physicians who received the intervention (% change in slope = -0.53, 95%CI = -2.34 to 1.30, p > .05). The main limitation of our study was the voluntary nature of the AD intervention, which may have introduced a self-selection bias of physicians most open to changing their prescribing. CONCLUSION: This study suggests that future AD interventions should focus on physicians with the greatest room for improvement to their prescribing.

Impact of a Transitional Pain Service on postoperative opioid trajectories: a retrospective cohort study.

INTRODUCTION: It has been well described that a small but significant proportion of patients continue to use opioids months after surgical discharge. We sought to evaluate postdischarge opioid use of patients who were seen by a Transitional Pain Service compared with controls. METHODS: We conducted a retrospective cohort study using administrative data of individuals who underwent surgery in Ontario, Canada from 2014 to 2018. Matched cohort pairs were created by matching Transitional Pain Service patients to patients of other academic hospitals in Ontario who were not enrolled in a Transitional Pain Service. Segmented regression was performed to assess changes in monthly mean daily opioid dosage. RESULTS: A total of 209 Transitional Pain Service patients were matched to 209 patients who underwent surgery at other academic centers. Over the 12 months after surgery, the mean daily dose decreased by an estimated 3.53 morphine milligram equivalents (95% CI 2.67 to 4.39, p<0.001) per month for the Transitional Pain Service group, compared with a decline of only 1.05 morphine milligram equivalents (95% CI 0.43 to 1.66, p<0.001) for the controls. The difference-in-difference change in opioid use for the Transitional Pain Service group versus the control group was -2.48 morphine milligram equivalents per month (95% CI -3.54 to -1.43, p=0.003). DISCUSSION: Patients enrolled in the Transitional Pain Service were able to achieve opioid dose reduction faster than in the control cohorts. The difficulty in finding an appropriate control group for this retrospective study highlights the need for future randomized controlled trials to determine efficacy.

Outcomes of Patent Foramen Ovale Transcatheter Closure: Should a Short Aortic Rim Preclude Closure?

Background: The risk of erosion of an atrial septal closure device, in particular the Amplatzer Septal Occluder, has been described as higher in patients with a short aortic rim. Similar concern has been applied to patent foramen ovale (PFO) closure devices, but there are only rare reported cases of erosion. It may be that smaller devices are chosen due to fear of device erosion in PFO patients when this is not necessarily an issue. Objectives: The authors aimed to assess outcomes after PFO closure with the Amplatzer PFO device in patients with a short (<9 mm) aortic rim. Methods: We performed a retrospective analysis of PFO closure for any indication, between 2006 and 2017 at a quaternary center. Preprocedural transesophageal echocardiographic parameters including the aortic rim were remeasured. Long-term outcomes were obtained by linkage to provincial administrative databases. Results: Over the study period, 324 patients underwent PFO closure with the Amplatzer PFO device, with a mean age of 49.8 years; 61% had a short aortic rim (<9 mm). The most common indication was cryptogenic stroke (72%); those with longer aortic distance were more likely to have a non-stroke indication for closure, diabetes (15% vs 6.5%, P = 0.04), and heart failure (15.7% vs 4%, P < 0.001). Over a median 7 years of follow-up, there were no cases of device erosion or embolization requiring cardiac surgery. Conclusions: In a large cohort with long-term administrative follow-up (1,394 patient-years), implantation of an Amplatzer PFO device was performed safely even in patients with a short aortic rim.

Introduction of publicly funded pharmacare and socioeconomic disparities in glycemic management in children and youth with type 1 diabetes in Ontario, Canada: a population-based trend analysis.

BACKGROUND: We evaluated the impact of publicly funded pharmacare (Ontario Health Insurance Plan [OHIP]+), which was introduced in Ontario on Jan. 1, 2018, for youth less than 25 years of age, on temporal trends in hemoglobin A1c (HbA1c, a measure of glycemic management) and the differential effect on the change in temporal trends in HbA1c according to socioeconomic status (SES). METHODS: We conducted a trend analysis using administrative data sets. We included youth aged 21 years, 9 months or younger, residing in Ontario on Jan. 1, 2016, with diabetes diagnosed before age 15 years and before Jan. 1, 2015. We used claims for insulin to measure pharmacare use. We evaluated the change in HbA1c (%) per 90 days before (Jan. 1, 2016, to Dec. 31, 2017) the introduction of and during (Apr. 1, 2018, to Mar. 31, 2019) OHIP+ coverage, and the difference in the change in HbA1c according to SES, using segmented regression analysis. RESULTS: Of 9641 patients, 7041 (73.0%) made an insulin claim. We found a negligible difference in the temporal change in HbA1c during compared with before OHIP+ coverage that was not statistically significant (ß estimate -0.0002, 95% confidence interval [CI] -0.0004 to 0.0000). The size of the effect was slightly greater in those individuals with the lowest SES than in those with the highest SES (ß estimate -0.0008, 95% CI -0.0015 to -0.0001). INTERPRETATION: We found that the effect of OHIP+ on the change in HbA1c was slightly greater for youth in the lowest SES than for those in the highest SES. Our findings suggest that publicly funded pharmacare may be an effective policy tool to combat worsening socioeconomic disparities in diabetes care and outcomes.