Characteristics of Opioid Toxicity Deaths Among Adolescents and Young Adults in Ontario Prior To and During the COVID-19 Pandemic.

PURPOSE: To characterize opioid toxicity deaths among adolescents and young adults in Ontario, Canada, prior to and during the first year of the COVID-19 pandemic. METHODS: We conducted a descriptive, cross-sectional study of opioid toxicity deaths among individuals aged 15-24 in Ontario in the year prior to (March 17, 2019, to March 16, 2020) and the first year of the pandemic (March 17, 2020, to March 16, 2021) using administrative health databases. We analyzed circumstances surrounding death, substances contributing to death, and health-care encounters prior to death. RESULTS: We identified 284 deaths among Ontarians aged 15-24, including 115 in the year preceding and 169 in the first year of the pandemic. Fentanyl contributed to 84.3% of deaths in the prepandemic year, rising to 93.5% (p = .012) the following year. Stimulants contributed to approximately half of deaths in both periods (41.7% prepandemic and 49.1% during pandemic). In both periods, roughly one in 4 decedents had a health-care encounter in the week prior to death and less than 20% of those with an opioid use disorder received opioid agonist treatment in the 30 days prior to death. DISCUSSION: Among young Ontarians, the number of opioid-related deaths increased by 47% in the first year of the COVID-19 pandemic. Fentanyl contributed to the vast majority of deaths, with non-opioid substances (primarily stimulants) also contributing to approximately half of deaths. Patterns of health-care utilization prior to death suggest opportunities to better connect this population to services that address opioid use disorder needs and promote harm reduction.

Risk of Arterial and Venous Thrombotic Events Among Patients with COVID-19: A Multi-National Collaboration of Regulatory Agencies from Canada, Europe, and United States.

Purpose: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. Patients and Methods: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE. Results: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09-0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99-1.04%) in the US. Conclusion: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability.

Cancer Screening Disparities Before and After the COVID-19 Pandemic.

Importance: Breast, cervical, and colorectal cancer-screening disparities existed prior to the COVID-19 pandemic, and it is unclear whether those have changed since the pandemic. Objective: To assess whether changes in screening from before the pandemic to after the pandemic varied for immigrants and for people with limited income. Design, Setting, and Participants: This population-based, cross-sectional study, using data from March 31, 2019, and March 31, 2022, included adults in Ontario, Canada, the country's most populous province, with more than 14 million people, almost 30% of whom are immigrants. At both dates, the screening-eligible population for each cancer type was assessed. Exposures: Neighborhood income quintile, immigrant status, and primary care model type. Main Outcomes and Measures: For each cancer screening type, the main outcome was whether the screening-eligible population was up to date on screening (a binary outcome) on March 31, 2019, and March 31, 2022. Up to date on screening was defined as having had a mammogram in the previous 2 years, a Papanicolaou test in the previous 3 years, and a fecal test in the previous 2 years or a flexible sigmoidoscopy or colonoscopy in the previous 10 years. Results: The overall cohort on March 31, 2019, included 1 666 943 women (100%) eligible for breast screening (mean [SD] age, 59.9 [5.1] years), 3 918 225 women (100%) eligible for cervical screening (mean [SD] age, 45.5 [13.2] years), and 3 886 345 people eligible for colorectal screening (51.4% female; mean [SD] age, 61.8 [6.4] years). The proportion of people up to date on screening in Ontario decreased for breast, cervical, and colorectal cancers, with the largest decrease for breast screening (from 61.1% before the pandemic to 51.7% [difference, -9.4 percentage points]) and the smallest decrease for colorectal screening (from 65.9% to 62.0% [difference, -3.9 percentage points]). Preexisting disparities in screening for people living in low-income neighborhoods and for immigrants widened for breast screening and colorectal screening. For breast screening, compared with income quintile 5 (highest), the ß estimate for income quintile 1 (lowest) was -1.16 (95% CI, -1.56 to -0.77); for immigrant vs nonimmigrant, the ß estimate was -1.51 (95% CI, -1.84 to -1.18). For colorectal screening, compared with income quintile 5, the ß estimate for quntile 1 was -1.29 (95% CI, 16 -1.53 to -1.06); for immigrant vs nonimmigrant, the ß estimate was -1.41 (95% CI, -1.61 to -1.21). The lowest screening rates both before and after the COVID-19 pandemic were for people who had no identifiable family physician (eg, moving from 11.3% in 2019 to 9.6% in 2022 up to date for breast cancer). In addition, patients of interprofessional, team-based primary care models had significantly smaller reductions in ß estimates for breast (2.14 [95% CI, 1.79 to 2.49]), cervical (1.72 [95% CI, 1.46 to 1.98]), and colorectal (2.15 [95% CI, 1.95 to 2.36]) postpandemic screening and higher uptake of screening in general compared with patients of other primary care models. Conclusions and Relevance: In this cross-sectional study in Ontario that included 2 time points, widening disparities before compared with after the COVID-19 pandemic were found for breast cancer and colorectal cancer screening based on income and immigrant status, but smaller declines in disparities were found among patients of interprofessional, team-based primary care models than among their counterparts. Policy makers should investigate the value of prioritizing and investing in improving access to team-based primary care for people who are immigrants and/or with limited income.

Validity of diagnoses of SARS-CoV-2 infection in Canadian administrative health data: a multiprovince, population-based cohort study.

BACKGROUND: Accurate coding of diagnoses of SARS-CoV-2 infection in administrative data benefits population-based studies about the epidemiology, treatment and outcomes of COVID-19. We describe the validity of diagnoses of SARS-CoV-2 infection recorded in hospital discharge abstracts, emergency department records and outpatient physician service claims from 3 Canadian provinces. METHODS: In this cohort study, population-based inpatient, emergency department and outpatient records were linked to SARS-CoV-2 polymerase chain reaction (PCR; reference standard) test results from British Columbia, Manitoba and Ontario for Apr. 1, 2020, to Mar. 31, 2021. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of diagnoses of SARS-CoV-2 infection were estimated for each quarter in the study period, overall and by province, age group and sex. RESULTS: Our study encompassed more than 13 million SARS-CoV-2 PCR test results. Specificity and NPV of diagnoses of SARS-CoV-2 infection were consistently high (i.e., most estimates were > 95%). Overall sensitivity estimates were 86.2%, 60.4% and 20.3% in the first quarter for inpatient, emergency department and outpatient cohorts, and 66.2%, 47.5% and 25.0% in the last quarter, respectively. For inpatients, overall PPV estimates ranged from 50.0% to 66.4%. For emergency department patients, overall PPV estimates were 76.9% and 68.3% in the first and last quarters, respectively. For outpatients, PPV estimates were 6.8% and 29.1% in the first and last quarters, respectively. INTERPRETATION: We found variations in the validity of diagnoses for SARS-CoV-2 infection recorded in different health care settings, geographic areas and over time. Our multiprovince validation study provides evidence about the potential use of inpatient and emergency department records as an alternative to population-based laboratory data for identification of patients with SARS-CoV-2 infection, but does not support the use of outpatient claims for this purpose.

Effect of Free Medicine Distribution on Health Care Costs in Canada Over 3 Years: A Secondary Analysis of the CLEAN Meds Randomized Clinical Trial.

Importance: Few interventions are proven to reduce total health care costs, and addressing cost-related nonadherence has the potential to do so. Objective: To determine the effect of eliminating out-of-pocket medication fees on total health care costs. Design, Setting, and Participants: This secondary analysis of a multicenter randomized clinical trial using a prespecified outcome took place across 9 primary care sites in Ontario, Canada (6 in Toronto and 3 in rural areas), where health care services are generally publicly funded. Adult patients (≥18 years old) reporting cost-related nonadherence to medicines in the past 12 months were recruited between June 1, 2016, and April 28, 2017, and followed up until April 28, 2020. Data analysis was completed in 2021. Interventions: Access to a comprehensive list of 128 medicines commonly prescribed in ambulatory care with no out-of-pocket costs for 3 years vs usual medicine access. Main Outcome and Measures: Total publicly funded health care costs over 3 years, including costs of hospitalizations. Health care costs were determined using administrative data from Ontario's single-payer health care system, and all costs are reported in Canadian dollars with adjustments for inflation. Results: A total of 747 participants from 9 primary care sites were included in the analysis (mean [SD] age, 51 [14] years; 421 [56.4%] female). Free medicine distribution was associated with a lower median total health care spending over 3 years of $1641 (95% CI, $454-$2792; P = .006). Mean total spending was $4465 (95% CI, -$944 to $9874) lower over the 3-year period. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, eliminating out-of-pocket medication expenses for patients with cost-related nonadherence in primary care was associated with lower health care spending over 3 years. These findings suggest that eliminating out-of-pocket medication costs for patients could reduce overall costs of health care. Trial Registration: ClinicalTrials.gov Identifier: NCT02744963.

Patterns of antiemetic medication use during pregnancy: A multi-country retrospective cohort study.

OBJECTIVE: To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014. METHODS: We constructed population-based cohorts of pregnant women using administrative healthcare data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Saskatchewan), the Clinical Practice Research Datalink from the United Kingdom, and the IBM MarketScan Research Databases from the United States. We included pregnancies ending in live births, stillbirth, spontaneous abortion, or induced abortion. We determined maternal use of antiemetics from pharmacy claims in Canada and the United States and from prescriptions in the United Kingdom. RESULTS: The most common outcome of 3 848 734 included pregnancies (started 2002-2014) was live birth (66.7% of all pregnancies) followed by spontaneous abortion (20.2%). Use of antiemetics during pregnancy increased over time in all three countries. Canada had the highest prevalence of use of prescription antiemetics during pregnancy (17.7% of pregnancies overall, 13.2% of pregnancies in 2002, and 18.9% in 2014), followed by the United States (14.0% overall, 8.9% in 2007, and 18.1% in 2014), and the United Kingdom (5.0% overall, 4.2% in 2002, and 6.5% in 2014). Besides use of antiemetic drugs being considerably lower in the United Kingdom, the increase in its use over time was more modest. The most commonly used antiemetic was combination doxylamine/pyridoxine in Canada (95.2% of pregnancies treated with antiemetics), ondansetron in the United States (72.2%), and prochlorperazine in the United Kingdom (63.5%). CONCLUSIONS: In this large cohort study, we observed an overall increase in antiemetic use during pregnancy, and patterns of use varied across jurisdictions. Continued monitoring of antiemetic use and further research are warranted to better understand the reasons for differences in use of these medications and to assess their benefit-risk profile in this population.

Tunable shape memory properties of highly stretchable poly(ester urea) random copolymers based on α-amino acids.

The exploration of biodegradable polymers with shape memory effects (SMEs) holds great promise in biomedical fields. Revealing the relationship between the SMEs and polymer structures not only contributes to interpreting the SME mechanisms, but also prompts the customization of materials properties for specific requirements. Herein, we developed a series of poly(ester urea) (PEU) random copolymers composed of two different diamine monomers based on L-alanine and L-valine, respectively. It was shown that the shape memory performance of the PEU copolymers strongly depended on the composition of two different diamine monomers in the PEU copolymers and other physical properties. This tunability likely arose from the change of polymer chain mobility and crystallinity, which were impacted by the choice of α-amino acids. Intriguingly, thin films of the PEU copolymers exhibited a high strain at break of 347-743% around the physiological temperature (35 °C). Moreover, the random copolymerization of two different sorts of diamine monomers has been demonstrated as a facile approach to precisely tailor the physical properties of the PEUs according to custom needs.

Association of Palliative Care with Days at Home and Healthcare Use in Patients with Advanced Chronic Obstructive Pulmonary Disease: A Cohort Study.

Rationale: Palliative care focuses on improving quality of life for patients with life-limiting conditions. Although previous studies have shown palliative care to be associated with reduced acute healthcare use in people with cancer and other illnesses, these findings may not generalize to patients with chronic obstructive pulmonary disease (COPD). Objectives: We examined the association between palliative care and rates of days at home, locations of death, and acute healthcare use in patients with COPD. Methods: We used health administrative databases in Ontario, Canada, to identify patients with advanced COPD hospitalized between April 2010 and March 2017 and followed up until March 2018. Patients who received palliative care were matched 1:1 with those who did not receive palliative care in terms of age, sex, long-term oxygen, previous COPD hospitalizations and propensity scores. Rate ratios (RR) were estimated by using Poisson models with generalized estimating equations to account for matching. Results: Among 35,492 patients, 1,788 (5%) received palliative care. In the matched cohort (1,721 pairs), people with COPD receiving palliative care had similar rates of days at home (RR, 1.01; 95% confidence interval [CI], 0.97-1.05) but were more likely to die at home (16.4% vs. 10.0%; P < 0.001) compared with those who did not receive palliative care. Rates of healthcare use were similar except for increased hospitalizations in the palliative care group (RR, 1.09; 95% CI, 1.01-1.18). Conclusions: Receipt of palliative care did not reduce days at home or healthcare use but was associated with a modest increase in the proportion who died at home. Future work should evaluate palliative care strategies designed specifically for patients with COPD.

Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort.

Importance: Ondansetron is frequently used to treat nausea and vomiting during pregnancy. Although some studies reported important safety signals, few studies have been sufficiently large to assess rare pregnancy outcomes. Objective: To study the association between ondansetron exposure during pregnancy and the risks of spontaneous abortion, stillbirth, and major congenital malformations. Design, Setting, and Participants: This is a cohort study conducted in 3 countries, with a meta-analysis. Participants included women and girls aged 12 to 55 years who experienced spontaneous abortion, induced abortion, stillbirth, or live birth between April 2002 and March 2016, as recorded in administrative data from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, and Ontario), the US IBM MarketScan Research Databases, and the UK Clinical Practice Research Datalink. The statistical analysis was completed in October 2020. Exposures: Exposure to ondansetron during pregnancy was compared with exposure to other commonly used antiemetics to minimize confounding by indication. Main Outcomes and Measures: The primary outcome was fetal death, defined as either spontaneous abortion or stillbirth. Secondary outcomes were the 2 components of the primary outcome and major congenital malformations identified during the year after a live birth. Adjusted hazard ratios were estimated using Cox proportional hazards models with time-dependent drug exposures and were adjusted using high-dimensional propensity scores. For major congenital malformations, adjusted odds ratios were estimated from logistic models. Site-level results were pooled using random-effects meta-analysis. Sensitivity analyses considered second-line antiemetic exposure and exposure specifically during 4 to 10 weeks of gestation. Results: Data from 456 963 pregnancies were included in this study of fetal death (249 787 [54.7%] in Canada, 197 913 [43.3%] in the US, and 9263 [2.0%] in the UK; maternal age, ≤24 years, 93 201 patients [20.4%]; 25-29 years, 149 117 patients [32.6%]; 30-34 years, 142 442 patients [31.2%]; and ≥35 years, 72 203 patients [15.8%]). Fetal death occurred in 12 907 (7.9%) of 163 810 pregnancies exposed to ondansetron, and 17 476 (5.7%) of 306 766 pregnancies exposed to other antiemetics. The adjusted hazard ratios were 0.91 (95% CI, 0.67-1.23) for fetal death with time-dependent ondansetron exposure during pregnancy, 0.82 (95% CI, 0.64-1.04) for spontaneous abortion, and 0.97 (95% CI, 0.79-1.20) for stillbirth. For major congenital malformations, the estimated odds ratio was 1.06 (95% CI, 0.91-1.22). Results of sensitivity analyses were generally consistent with those of the primary analyses. Conclusions and Relevance: In this large, multicenter cohort study, there was no association between ondansetron exposure during pregnancy and increased risk of fetal death, spontaneous abortion, stillbirth, or major congenital malformations compared with exposure to other antiemetic drugs.

Shifts in office and virtual primary care during the early COVID-19 pandemic in Ontario, Canada.

BACKGROUND: Globally, primary care changed dramatically as a result of the coronavirus disease 2019 (COVID-19) pandemic. We aimed to understand the degree to which office and virtual primary care changed, and for which patients and physicians, during the initial months of the pandemic in Ontario, Canada. METHODS: This population-based study compared comprehensive, linked primary care physician billing data from Jan. 1 to July 28, 2020, with the same period in 2019. We identified Ontario residents with at least 1 office or virtual (telephone or video) visit during the study period. We compared trends in total physician visits, office visits and virtual visits before COVID-19 with trends after pandemic-related public health measures changed the delivery of care, according to various patient and physician characteristics. We used interrupted time series analysis to compare trends in the early and later halves of the COVID-19 period. RESULTS: Compared with 2019, total primary care visits between March and July 2020 decreased by 28.0%, from 7.66 to 5.51 per 1000 people/day. The smallest declines were among patients with the highest expected health care use (8.3%), those who could not be attributed to a primary care physician (10.2%), and older adults (19.1%). In contrast, total visits in rural areas increased by 6.4%. Office visits declined by 79.1% and virtual care increased 56-fold, comprising 71.1% of primary care physician visits. The lowest uptake of virtual care was among children (57.6%), rural residents (60.6%) and physicians with panels of ≥ 2500 patients (66.0%). INTERPRETATION: Primary care in Ontario saw large shifts from office to virtual care over the first 4 months of the COVID-19 pandemic. Total visits declined least among those with higher health care needs. The determinants and consequences of these major shifts in care require further study.

Identification of incident pancreatic cancer in Ontario administrative health data: A validation study.

PURPOSE: To validate three approaches for identifying incident cases of pancreatic cancer in Ontario administrative claims data. METHODS: We created a cohort using Ontario (Canada) administrative health data from 2002 to 2012 and identified cases of pancreatic cancer with three approaches, using the Ontario Cancer Registry (OCR) as the reference standard. In the any diagnosis approach, cases were defined by primary or secondary diagnostic codes for pancreatic cancer in outpatient or inpatient records. In the any inpatient diagnosis approach, cases were defined using only diagnoses in hospital discharge abstracts. In the algorithm approach, cases were identified by an algorithm that combined the first two approaches. Comparing each approach to the OCR, we calculated the expected value and 95% confidence interval (CI) of the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We also compared the event dates using each approach with those recorded in the OCR. RESULTS: Among a total of 12 060 837 patients in Ontario administrative health data sources, 13 999 incident pancreatic cancer cases were identified in the OCR. Sensitivity ranged from 72.5% (algorithm) to 97.5% (any diagnosis), and PPV ranged from 38.4% (any diagnosis) to 78.9% (any inpatient diagnosis). Specificity and NPV were ~100% for all approaches. The median absolute difference in cancer event date ranged 0 to 15 days. The any inpatient diagnosis method had the highest PPV (78.9%; 95% CI: 78.2-79.5%) and moderate sensitivity (86.6%; 95% CI: 86.0-87.2%). CONCLUSION: Inpatient diagnoses of pancreatic cancer in Ontario administrative heath data are suitable for pancreatic cancer case identification.

Statins and renovascular disease in the elderly: a population-based cohort study.

AIMS: More than 90% of cases of renovascular disease (RVD) are caused by atherosclerosis; thus patients with this condition are at high risk for vascular events. We examined the association of statins with prognosis in patients with RVD. METHODS AND RESULTS: We performed a population-based cohort study in 4040 patients with RVD older than 65 years using province-wide health data in Ontario, Canada. The primary outcome was time to first cardiorenal event, specifically myocardial infarction, stroke, heart failure, acute renal failure, dialysis or death; the primary analysis used a time-dependent covariate for statin exposure. Despite having a greater burden of cardiovascular and renal comorbidity, the risk of the primary outcome was significantly lower in statin users than in non-users [unadjusted hazard ratio (HR) 0.51, 95% confidence interval (CI) 0.47-0.57; P < 0.0001]. This association was materially unchanged after adjusting for demographic characteristics, cardiovascular risk factors, other comorbidities, measures of health-care utilization, screening, and concomitant medications (adjusted HR 0.51, 95% CI 0.46-0.57). An analysis using the same endpoint in a propensity-matched cohort without time-dependent statin exposure revealed a lower risk of the primary outcome in statin-treated patients but with a substantially more conservative point estimate (HR 0.82, 95% CI 0.71-0.95). CONCLUSION: These data suggest that statins are associated with improved prognosis in elderly patients with RVD.

Investigation of corrosion caused by constituents of refinery wastewater effluent used as circulating cooling water.

The corrosion rate of steel plate using single-factor, multifactor, and complex water systems was investigated via refinery wastewater effluents used as circulating cooling water. The results show that the primary corrosion factors of steel depend on the characteristics of the ions, the formation of the oxidized coating, the diffusion of dissolved oxygen, and other complex factors, although ions such as chloride, calcium, and carbonate play an important role. The corrosion rate of carbon steel exhibits two trends: The corrosion rate is high at low conductivity, increases to a maximum, and then decreases and becomes stable with increasing conductivity, as is the case with chloride, sulfate, nitrate and calcium ions. On the other hand, the corrosion rate is highest at low conductivity and then decreases and becomes stable with increasing conductivity, as is the case with carbonate, silicate, and sodium nitrate ions. Research results indicate that the anticorrosive ability is minimal at low conductivity; but is excellent at high conductivity. Pretreatment of low-conductivity water using air flotation and clarification to decrease the concentrations of chloride, calcium, and carbonate ions to a suitable level to satisfy the anticorrosion requirements is required. However, it is not necessary to significantly reduce the salt concentration or conductivity of the water by osmosis or ion exchange to obtain an anticorrosion effect when reusing wastewater effluents as circulating cooling water.