Opioid-related deaths between 2019 and 2021 across 9 Canadian provinces and territories.

BACKGROUND: The drug toxicity crisis continues to accelerate across Canada, with rapid increases in opioid-related harms following the onset of the COVID-19 pandemic. We sought to describe trends in the burden of opioid-related deaths across Canada throughout the pandemic, comparing these trends by province or territory, age, and sex. METHODS: We conducted a repeated cross-sectional analysis of accidental opioid-related deaths between Jan. 1, 2019, and Dec. 31, 2021, across 9 Canadian provinces and territories using aggregated national data. Our primary measure was the burden of premature opioid-related death, measured by potential years of life lost. Our secondary measure was the proportion of all deaths attributable to opioids; we used the Cochrane-Armitage test for trend to compare proportions. RESULTS: Between 2019 and 2021, the annual number of opioid-related deaths increased from 3007 to 6222 and years of life lost increased from 126 115 to 256 336 (from 3.5 to 7.0 yr of life lost per 1000 population). In 2021, the highest number of years of life lost was among males (181 525 yr) and people aged 30-39 years (87 045 yr). In 2019, we found that 1.7% of all deaths among those younger than 85 years were related to opioids, rising to 3.2% in 2021. Significant increases in the proportion of deaths related to opioids were observed across all age groups (p < 0.001), representing 29.3% and 29.0% of deaths among people aged 20-29 and 30-39 years in 2021, respectively. INTERPRETATION: Across Canada, the burden of premature opioid-related deaths doubled between 2019 and 2021, representing more than one-quarter of deaths among younger adults. The disproportionate loss of life in this demographic group highlights the critical need for targeted prevention efforts.

Trends in opioid toxicities among people with and without opioid use disorder and the impact of the COVID-19 pandemic in Ontario, Canada: A population-based analysis.

BACKGROUND: Across Canada, the COVID-19 pandemic occurred amidst an ongoing drug toxicity crisis. Although elevated rates of substance-related harms have been observed nationally, it remains unknown if the pandemic state of emergency led to disproportionate increases in opioid toxicities among people with opioid use disorder (OUD) compared to those without. METHODS: We conducted a population-based repeated cross-sectional time series analysis of fatal and non-fatal opioid toxicities between January 1, 2014, and December 31, 2021, in Ontario, Canada. We used interventional autoregressive integrated moving average models to examine the impact of the pandemic on monthly rates of opioid toxicities per 100,000 Ontario residents stratified by people with and without OUD. RESULTS: We identified 80,296 opioid toxicities of which 53.5 % occurred among people with OUD. Among 52,052 unique individuals, 60.5 % were male and 46.2 % were 25-44 years old. Between January 2014 and December 2021, the rate of opioid toxicities increased from 2.6 to 10.5 per 100,000 (rate ratio [RR]=4.07). The magnitude of this increase differed among people with OUD (0.8 to 7.4 per 100,000; RR=9.35) and without OUD (1.8 to 3.1 per 100,000; RR=1.74). We observed a significant ramp increase in the overall rate of opioid toxicities following the declaration of the pandemic emergency in March 2020 (+0.19 per 100,000 monthly, 95 % CI: 0.029, 0.36, p = 0.021). In a stratified analysis, we found a similar ramp increase among people with OUD (+0.19 per 100,000 monthly, 95 % CI: 0.10, 0.28, p < 0.001); however, this was not observed among people without OUD (p = 0.95). CONCLUSIONS: The rate of opioid toxicities accelerated across Ontario following the pandemic-related state of emergency, with the majority of this increase among people with OUD. The important differences observed among people with OUD compared with those without, highlights the critical need for improved access to harm reduction and treatment interventions among this population.

Prescribed safer opioid supply: A scoping review of the evidence.

BACKGROUND: Safer opioid supply programs provide prescription pharmaceutical opioids, often with supportive services, to people at high risk of experiencing harms related to substance use. However, questions regarding the effectiveness and safety of this practice remain. We conducted a scoping review of literature describing client outcomes from formal opioid supply programs providing prescriptions for pharmaceutical opioids, and the perceptions of involved clients/providers. METHODS: We performed a scoping review of peer-reviewed studies and grey literature published between January 1, 2012, to September 12, 2023. We included articles reporting either safer opioid supply client outcomes or clients/providers perspectives. Extracted data included study objectives, substance use patterns, client outcomes, client/provider perspectives, and estimates of effectiveness and/or harm. RESULTS: Our search yielded 1,597 articles. Following removal of duplicates and application of exclusion criteria, 24 publications comprising 17 peer-reviewed and seven grey literature publications were included in our study. We generated eight themes summarizing topics in the available literature: opioid-related toxicities, infectious complications, other clinical outcomes, client-reported outcomes, program access barriers, diversion, program retention, and costs to the healthcare system. Specific findings included low rates of opioid toxicities, improved physical and mental health, and improved quality of life among clients. A lack of access to adequate opioid doses and the limited range of opioid options offered within safer opioid supply programs was described by clients and providers as a potential reason for diversion and a barrier to program access. CONCLUSIONS: Generally, evidence suggests that safer opioid supply programs are beneficial to clients through measurable outcomes. However, the available literature has important limitations, including limited inferences about the effectiveness, safety, and potential for diversion within safer opioid supply programs. Further research is needed to support the ongoing evaluation of safer opioid supply programs as one component of a multifactorial response to escalating rates of substance-related harms.

Assessing the impact of the slow-release oral morphine drug shortages in Ontario, Canada: A population-based time series analysis.

BACKGROUND: Slow-release oral morphine (SROM) is used to manage pain, and as opioid agonist treatment (OAT). Between 2017 and 2021 in Canada, several drug shortages occurred for Kadian© (SROM-24). The purpose of this study was to evaluate the impact of these shortages on people's ability to remain on this medication. METHODS: We conducted a retrospective population-based time series analysis of SROM-24 dispensed between January 1, 2014, and December 31, 2021, in Ontario, Canada. Using interventional autoregressive integrated moving average models (ARIMA) models, we evaluated the association between SROM-24 drug shortages and treatment discontinuation. Analyses were also stratified by the SROM-24 indication (pain or OAT). RESULTS: We identified 22,479 SROM-24 recipients, of which one-third (33.9%) were aged 65 or above and just over half (51.9%) were female. In our primary analysis of monthly SROM-24 discontinuation, we observed a significant sustained monthly increase following the shortages in November 2019 (+0.29%/month; 95% CI: 0.16%, 0.43%; p < .001) with significant sudden, temporary changes following the shortages in March 2020 (+2.00%; 95% CI: 0.95%, 3.05%; p < .001), July 2021 (+3.53%; 95% CI: 2.20%, 4.86%; p < .001), and August 2021 (+4.98%; 95% CI: 3.49%, 6.47%; p < .001). Similar results were observed in our stratified analyses, with sustained high rates of discontinuation among people accessing SROM-24 as OAT. CONCLUSIONS: The SROM-24 shortages resulted in significant treatment disruptions across all recipients. These findings have important implications for those with few treatment alternatives, including people using SROM-24 as OAT who are at risk of adverse outcomes following treatment disruptions.

Trends in Opioid Toxicity-Related Deaths in the US Before and After the Start of the COVID-19 Pandemic, 2011-2021.

Importance: Opioid-related harms constitute a major public health crisis in the US, and this crisis has worsened during the COVID-19 pandemic. Objectives: To characterize the societal burden of unintentional opioid-related deaths in the US and describe changing mortality patterns during the COVID-19 pandemic. Design, Setting, and Participants: A serial cross-sectional study examined all unintentional opioid-related deaths in the US, evaluated annually from calendar years 2011 to 2021. Main Outcomes and Measures: The public health burden of opioid toxicity-related deaths was estimated in 2 ways. First, the proportion of all deaths that were attributable to unintentional opioid toxicity by year (2011, 2013, 2015, 2017, 2019, and 2021) and age group (15-19, 20-29, 30-39, 40-49, 50-59, and 60-74 years) were calculated, using age-specific estimates of all-cause mortality as the denominator. Second, the total years of life lost (YLL) due to unintentional opioid toxicity was estimated, overall and by sex and age group, for each year studied. Results: Among the 422 605 unintentional deaths due to opioid toxicity between 2011 and 2021, the median age of the individuals was 39 (IQR, 30-51) years, and 69.7% were male. The number of unintentional deaths due to opioid toxicity increased 289% over the study period, from 19 395 (2011) to 75 477 (2021). Similarly, the percentage of all deaths that were attributed to opioid toxicity increased from 1.8% in 2011 to 4.5% in 2021. By 2021, opioid toxicity was responsible for 10.2% of all deaths among those aged 15 to 19 years, 21.7% of deaths among those aged 20 to 29 years, and 21.0% of deaths among those aged 30 to 39 years. The YLL due to opioid toxicity increased 276% over the study period, from 777 597 in 2011 to 2 922 497 in 2021. While YLL plateaued between 2017 (7.0 YLL per 1000) and 2019 (7.2 YLL per 1000), it increased by 62.9% between 2019 and 2021 coincident with the COVID-19 pandemic, reaching 11.7 YLL per 1000 population. This relative increase was similar across all age groups and sexes with the exception of those aged 15 to 19 years, in whom the YLL nearly tripled, from 1.5 to 3.9 YLL per 1000 population. Conclusions and Relevance: In this cross-sectional study, deaths due to opioid toxicity increased substantially during the COVID-19 pandemic. By 2021, 1 of every 22 deaths in the US was attributable to unintentional opioid toxicity, underscoring the urgent need to support people at risk of substance-related harm, particularly men, younger adults, and adolescents.

Medication errors in community pharmacies: Evaluation of a standardized safety program.

Background: The mandated reporting of medication-related errors in community pharmacies including incidents resulting in inappropriate medication use and near misses intercepted before reaching the patient can be utilized as learning opportunities to aid in the prevention of future events. Objectives: To examine reporting uptake, trends, and initial learnings from medication errors reported by community pharmacists to the Assurance and Improvement in Medication Safety (AIMS) Program based in Ontario, Canada between April 1st, 2018, and June 30th, 2021. Methods: A descriptive analysis was conducted of all events reported to the AIMS Program during the study period. The web-based reporting form includes a series of mandatory and optional fields completed by the reporter. Individual medications were grouped into broader classes prior to conducting the analysis. Results: Among the 31,768 event reports received from 2856 community pharmacies, there were 19,639 incidents and 12,129 near misses. Low reporting followed by a rapid increase was observed during expansion of the AIMS Program in 2018, with almost 60% of Ontario community pharmacies submitting at least 1 event over the study period. In most cases (90.5%), no patient harm was reported. The most frequent event types involved the incorrect drug (19.5%), concentration (17.2%) or quantity (14.5%). Approximately 25% of events were identified by the involved patient or their agent. When looking at medication classes, antihypertensives, opioids and antidepressants were involved in over one-quarter of overall and higher severity events. Environmental staffing problems and interruptions were the contributory factor and sub-factor most frequently reported, respectively. Conclusions: This study provides insights into engagement with the AIMS Program by Ontario community pharmacy teams since implementation in 2018. The identification of the circumstances and medications associated with both incidents and near misses, aids in the continued development of strategies and processes to help prevent future events.

Yellow fever vaccine usage in the United States and risk of neurotropic and viscerotropic disease: A retrospective cohort study using three healthcare databases.

BACKGROUND: Yellow fever (YF) vaccines are highly effective and have a well-established safety profile despite the risk of rare serious adverse events (SAEs), vaccine-associated neurotropic (YEL-AND) and viscerotropic disease (YEL-AVD). This study aimed to describe US civilian YF vaccine usage, the population characteristics and pre-existing immunosuppressive medical conditions among those vaccinated, and to provide updated risk estimates of neurotropic and viscerotropic disease post-vaccination. METHODS: A retrospective cohort study was conducted using de-identified patient information from Optum Electronic Healthcare Record (EHR) (2007-2019), Optum Clinformatics Data Mart (CDM) (2004-2019) and IBM MarketScan (2007-2019) databases. YF vaccine recipients were identified using relevant vaccination and procedural codes. Demographic characteristics and pre-existing medical conditions were described. Incidence proportions with 95% confidence intervals (CI) of neurotropic and viscerotropic diseases occurring ≤ 30 days post-vaccination, after exclusion of unlikely cases based on current clinical guidelines of YEL-AND and YEL-AVD, were calculated. RESULTS: A total of 92,205, 46,539 and 125,235 YF vaccine recipients were retrieved from Optum EHR, Optum CDM and IBM MarketScan databases, respectively. The majority of vaccine recipients were aged < 60 years (highest proportion aged 18-29 years) with a higher proportion of females overall. Few vaccine recipients (<1%) had conditions predisposing them to immunosuppression. Four non-fatal cases of neurotropic disease and zero cases of viscerotropic disease were identified. The incidence proportion of post-vaccination neurotropic disease was 1.41 (95% CI: 0.15-6.61) and 3.04 (95% CI: 0.86-8.11) per 100,000 vaccine recipients in Optum EHR and IBM MarketScan, respectively, with no events identified in Optum CDM. CONCLUSIONS: This study provides updated insights into current YF vaccine usage in US civilian recipients and supports the safety profile of YF vaccines in US practice. The low frequency of pre-existing immunosuppressive medical conditions among vaccine recipients suggests good adherence to vaccination guidelines by healthcare practitioners. The risk of developing neurotropic and viscerotropic disease post-vaccination remains rare.

Improved post-marketing safety surveillance of quadrivalent inactivated influenza vaccine in Mexico using a computerized, SMS-based follow-up system.

Quadrivalent influenza vaccines (QIVs) are designed to prevent influenza disease caused by two influenza A viruses (H1N1 and H3N2) and both influenza B lineages. Risk-monitoring of QIVs to identify adverse events (AEs) is necessary as influenza vaccines are reformulated each year. We developed a new active surveillance system (Sistema de Control de Vacunación; SICOVA) to improve pharmacovigilance in Mexico. Participants (N = 2013) aged 0 - 96 years from nine sites across three influenza seasons (n = 1166 in 2015 - 2016; n = 633 in 2016 - 2017; and n = 214 in 2017 - 2018) agreed to receive text messages 1, 7, 28, and 42 days post-vaccination to know if they had experienced any AEs. The study was completed electronically by 1763 (87.6%) participants; manual follow-up was conducted for 250 participants whose reporting was incomplete. The overall AE rate was 9.09%. At least one AE was reported by 183 participants, of whom 131 (71.58%) did not require a medical visit and 52 (28.42%) needed medical attention, with none requiring hospitalization. Most AEs requiring medical attention occurred in children aged 0 - 5 years (n = 22, 42.31%) and adults aged 31 - 35 years (n = 5, 9.62%). These results are consistent with the established safety profile of Fluzone® Quadrivalent, and show that SICOVA can facilitate surveillance and increase AE reporting in Mexico.

Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry.

BACKGROUND: The Fluzone® Quadrivalent (IIV4, Sanofi Pasteur) Pregnancy Registry was created to monitor vaccine safety during pregnancy (clinicaltrials.gov, NCT01945424). Here, we describe maternal, pregnancy, obstetrical and neonatal outcomes after vaccine exposure in pregnant women between August 2013 and September 2019. METHODS: All women exposed to IIV4 during their pregnancy were eligible for inclusion. Outcomes were prospective (reported following vaccine exposure but before knowledge of pregnancy outcome ascertained through prenatal tests) or retrospective (prenatal tests were undertaken before the exposure was reported). RESULTS: Among 239 IIV4 vaccine exposure reports received, there were 105 prospective and 10 retrospective reports of maternal adverse events (AEs). The most frequent prospectively reported maternal AEs were medication errors (expired product [n = 8, 3.8%]; extra dose [n = 7, 3.3%]) and injection site pain (n = 7, 3.3%). Among 62 prospectively reported pregnancy and obstetrical events with available follow-up information, seven AEs were reported, four (6.4%) of which were spontaneous abortions. A further seven AEs were reported among the 29 retrospective pregnancy and obstetrical events with available follow-up information. Among neonatal outcomes (15 prospective; 28 retrospective), >85% were reported as full-term births. One premature birth was reported prospectively. Four other neonatal AEs were reported, all retrospectively: two cases of talipes (club foot), one central nervous system anomaly and one atrial septal defect. All infants with available information had normal APGAR scores at 5 minutes. CONCLUSIONS: The frequency of AEs following exposure to IIV4 during pregnancy did not indicate new safety concerns.