Physiologic oxygen responses to smoking opioids: an observational study using continuous pulse oximetry at overdose prevention services in British Columbia, Canada.

BACKGROUND: In British Columbia, Canada, smoking is the most common modality of drug use among people who die of opioid toxicity. We aimed to assess oxygen saturation (SpO2) while people smoked opioids during a pilot study that introduced continuous pulse oximetry at overdose prevention services (OPS) sites. METHODS: This was an observational cohort study, using a participatory design. We implemented our monitoring protocol from March to August 2021 at four OPS. We included adults (≥ 18 years) presenting to smoke opioids. A sensor taped to participants' fingers transmitted real-time SpO2 readings to a remote monitor viewed by OPS staff. Peer researchers collected baseline data and observed the timing of participants' inhalations. We analyzed SpO2 on a per-event basis. In mixed-effects logistic regression models, drop in minimum SpO2 ≤ 90% in the current minute was our main outcome variable. Inhalation in that same minute was our main predictor. We also examined inhalation in the previous minute, cumulative inhalations, inhalation rate, demographics, co-morbidities, and substance use variables. RESULTS: We recorded 599 smoking events; 72.8% (436/599) had analyzable SpO2 data. Participants' mean age was 38.6 years (SD 11.3 years) and 73.1% were male. SpO2 was highly variable within and between individuals. Drop in SpO2 ≤ 90% was not significantly associated with inhalation in that same minute (OR: 1.2 [0.8-1.78], p = 0.261) or inhalation rate (OR 0.47 [0.20-1.10], p = 0.082). There was an association of SpO2 drop with six cumulative inhalations (OR 3.38 [1.04-11.03], p = 0.043); this was not maintained ≥ 7 inhalations. Demographics, co-morbidities, and drug use variables were non-contributory. CONCLUSIONS: Continuous pulse oximetry SpO2 monitoring is a safe adjunct to monitoring people who smoke opioids at OPS. Our data reflect challenges of real-world monitoring, indicating that greater supports are needed for frontline responders at OPS. Inconsistent association between inhalations and SpO2 suggests that complex factors (e.g., inhalation depth/duration, opioid tolerance, drug use setting) contribute to hypoxemia and overdose risk while people smoke opioids.

Feeling safer: effectiveness, feasibility, and acceptability of continuous pulse oximetry for people who smoke opioids at overdose prevention services in British Columbia, Canada.

BACKGROUND: Smoking is the most common mode of unregulated opioid consumption overall and implicated in fatal overdoses in British Columbia (BC). In part, perception of decreased risk (e.g., fewer who smoke carry naloxone kits) and limited smoking-specific harm reduction services contribute to overdose deaths. Overdose prevention services (OPS) offer supervised settings for drug use. Continuous pulse oximetry, common in acute care, allows real-time, remote oxygen monitoring. We evaluated the effectiveness of a novel continuous pulse oximetry protocol aimed at allowing physical distancing (as required by COVID-19, secluded spaces, and to avoid staff exposure to vaporized opioids), its feasibility, and acceptability at OPS for people who smoke opioids. METHODS: This was a mixed methods survey study. We developed a continuous pulse oximetry protocol in collaboration with clinical experts and people with lived/living experience of substance use. We implemented our protocol from March to August 2021 at four OPS in BC permitting smoking. We included adults (≥ 18 years) presenting to OPS to smoke opioids. Peer researchers collected demographic, health, and substance use information, and conducted structured observations. OPS clients participating in our study, OPS staff, and peer researchers completed post-monitoring surveys. We analyzed responses using a thematic inductive approach and validated themes with peer researchers. RESULTS: We included 599 smoking events. OPS clients participating in our study had a mean age of 38.5 years; 73% were male. Most (98%) reported using "down", heroin, or fentanyl; 48% concurrently used other substances (32% of whom reported stimulants); 76% reported smoking alone in the last 3 days; and 36% reported an overdose while smoking. Respondents reported that the protocol facilitated physical distancing, was easy to use, high satisfaction, improved confidence, improved sense of safety, and that they would use it again. CONCLUSIONS: Continuous pulse oximetry allowed safe physical distancing, was feasible, and acceptable in monitoring people who smoke opioids at OPS.

Health system use and outcomes of urgently triaged callers to a nurse-managed telephone service for provincial health information after initiation of supplemental virtual physician assessment: a descriptive study.

BACKGROUND: British Columbia's 8-1-1 telephone service connects callers with nurses for health care advice. As of Nov. 16, 2020, callers advised by a registered nurse to obtain in-person medical care can be subsequently referred to virtual physicians. We sought to determine health system use and outcomes of 8-1-1 callers urgently triaged by a nurse and subsequently assessed by a virtual physician. METHODS: We identified callers referred to a virtual physician between Nov. 16, 2020, and Apr. 30, 2021. After assessment, virtual physicians assigned callers to 1 of 5 triage dispositions (i.e., go to emergency department [ED] now, see primary care provider within 24 hours, schedule an appointment with a health care provider, try home treatment, other). We linked relevant administrative databases to ascertain subsequent health care use and outcomes. RESULTS: We identified 5937 encounters with virtual physicians involving 5886 8-1-1 callers. Virtual physicians advised 1546 callers (26.0%) to go to the ED immediately, of whom 971 (62.8%) had 1 or more ED visits within 24 hours. Virtual physicians advised 556 (9.4%) callers to seek primary care within 24 hours, of whom 132 (23.7%) had primary care billings within 24 hours. Virtual physicians advised 1773 (29.9%) callers to schedule an appointment with a health care provider, of whom 812 (45.8%) had primary care billings within 7 days. Virtual physicians advised 1834 (30.9%) callers to try a home treatment, of whom 892 (48.6%) had no health system encounters over the next 7 days. Eight (0.1%) callers died within 7 days of assessment with a virtual physician, 5 of whom were advised to go to the ED immediately. Fifty-four (2.9%) callers with a "try home treatment" disposition were admitted to hospital within 7 days of a virtual physician assessment, and no callers who were advised home treatment died. INTERPRETATION: This Canadian study evaluated health service use and outcomes arising from the addition of virtual physicians to a provincial health information telephone service. Our findings suggest that supplementation of this service with an assessment from a virtual physician safely reduces the overall proportion of callers advised to seek urgent in-person visits.

The impact of poisoning in British Columbia: a cost analysis.

BACKGROUND: Poisoning, from substances such as illicit drugs, prescribed and over-the-counter medications, alcohol, pesticides, gases and household cleaners, is the leading cause of injury-related death and the second leading cause for injury-related hospital admission in British Columbia. We examined the health and economic costs of poisoning in BC for 2016, using a societal perspective, to support public health policies aimed at minimizing losses to society. METHODS: Costs by intent, sex and age group were calculated in Canadian dollars using a classification and costing framework based on existing provincial injury data combined with data from the published literature. Direct cost components included fatal poisonings, hospital admissions, emergency department visits, ambulance attendance without transfer to hospital and calls to the British Columbia Drug and Poison Information Centre (BC DPIC) not resulting in ambulance attendance, emergency care or transfer to hospital. Indirect costs, measured as loss of earnings and informal caregiving costs, were also calculated. RESULTS: We estimate that poisonings in BC totalled $812.5 million in 2016 with $108.9 million in direct health care costs and $703.6 million in indirect costs. Unintentional poisoning injuries accounted for 84% of total costs, 46% of direct costs and 89% of indirect costs. Males accounted for higher proportions of direct costs for all patient dispositions except hospital admissions. Patients aged 25-64 years accounted for higher proportions of direct costs except for calls to BC DPIC, where proportions were highest for children younger than 15 years. INTERPRETATION: Hospital care expenditures represented the largest direct cost of poisoning, and lost productivity following death represented the largest indirect cost. Quantifying and understanding the financial burden of poisoning has implications not only for government and health care, but also for society, employers, patients and families.

Out-of-hospital management of unresponsive, apneic, witnessed opioid overdoses: a case series from a supervised consumption site.

OBJECTIVES: There are conflicting recommendations for lay rescuer management of patients who are unresponsive and apneic due to opioid overdose. We evaluated the management of such patients at an urban supervised consumption site. METHODS: At a single urban supervised consumption site in Vancouver, BC, we conducted a retrospective chart review and administrative database linkage of consecutive patients who were unresponsive and apneic following witnessed opioid overdose between January 1, 2012 and December 31, 2017. We linked these visits with regional hospital records to define the entire care episode, which concluded when the patient was discharged from the supervised consumption site, ED, or hospital, or died. The primary outcome was successful resuscitation, defined as alive and neurologically intact (ambulatory and speaking coherently, or alert and oriented, or Glasgow Coma Scale 15) at the conclusion of the care episode. Secondary outcomes included mortality and predefined complications of resuscitation. RESULTS: We collected 767 patients, with a median age of 43 and 81.6% male, with complete follow-up on 763 patients (99.5%). All patients were managed with oxygen and ventilation (100%, 95% CI 0.995-1.0); 715 (93.2%, 95% CI 0.911-0.949) received naloxone; no patients underwent chest compressions (0%, 95% CI 0-0.005). All patients with complete follow-up were alive and neurologically intact at the end of their care episode (100%, 95% CI 0.994-1.0). Overall, 191 (24.9%) patients were transported to hospital, and 15 (2.0%) patients required additional naloxone after leaving the supervised consumption site; 16 (2.1%) developed complications, and 1 patient was admitted to hospital. CONCLUSIONS: At an urban supervised consumption site, all unresponsive, apneic patients with witnessed opioid overdose were successfully resuscitated with oxygen and/or naloxone. No patients required chest compressions.

RéSUMé: OBJECTIFS: Il existe des recommandations contradictoires concernant la prise en charge par des secouristes non professionnels des patients qui ne réagissent pas et sont apnéiques en raison d'une surdose d'opioïdes. Nous avons évalué la prise en charge de ces patients dans un site urbain de consommation supervisée. MéTHODES: Dans un seul site de consommation supervisée urbain à Vancouver, en Colombie-Britannique, nous avons effectué un examen rétrospectif des dossiers et un couplage de bases de données administratives de patients consécutifs qui étaient insensibles et apnéiques après avoir été témoins d'une surdose d'opioïdes entre le 1er janvier 2012 et le 31 décembre 2017. Le résultat primaire était la réussite de la réanimation, définie comme étant vivante et neurologiquement intacte (ambulatoire et parlant de manière cohérente, ou alerte et orientée, ou échelle de coma de Glasgow 15) à la fin de l'épisode de soins. Les résultats secondaires comprenaient la mortalité et les complications prédéfinies de la réanimation. RéSULTATS: Nous avons recueilli 767 patients, avec un âge médian de 43 ans et 81,6 % d'hommes, avec un suivi complet de 763 patients (99,5 %). Tous les patients ont été pris en charge avec de l'oxygène et la ventilation (100 %, IC à 95 % : 0,995-1,0) ; 715 (93,2 %, IC à 95 % : 0,911-0,949) ont reçu de la naloxone ; aucun patient n'a subi de compressions thoraciques (0 %, IC à 95 % : 0-0,005). Tous les patients ayant fait l'objet d'un suivi complet étaient vivants et intacts sur le plan neurologique à la fin de leur épisode de soins (100 %, IC à 95 % : 0,994-1,0). Dans l'ensemble, 191 (24,9 %) patients ont été transportés à l'hôpital, et 15 (2,0 %) patients ont eu besoin de naloxone supplémentaire après avoir quitté le site de consommation supervisée ; 16 (2,1 %) ont développé des complications, et 1 patient a été admis à l'hôpital. CONCLUSIONS: Dans un centre de consommation supervisée urbain, tous les patients apnéiques non réceptifs ayant été témoins d'une surdose d'opioïdes ont été réanimés avec succès avec de l'oxygène et/ou de la naloxone. Aucun patient n'a eu besoin de compressions thoraciques.

Association Between Prescription Opioid Therapy for Noncancer Pain and Hepatitis C Virus Seroconversion.

Importance: Initiation of injection drug use may be more frequent among people dispensed prescription opioid therapy for noncancer pain, potentially increasing the risk of hepatitis C virus (HCV) acquisition. Objective: To assess the association between medically dispensed long-term prescription opioid therapy for noncancer pain and HCV seroconversion among individuals who were initially injection drug use-naive. Design, Setting, and Participants: A population-based, retrospective cohort study of individuals tested for HCV in British Columbia, Canada, with linkage to outpatient pharmacy dispensations, was conducted. Individuals with an initial HCV-negative test result followed by 1 additional test between January 1, 2000, and December 31, 2017, and who had no history of substance use at baseline (first HCV-negative test), were included. Participants were followed up from baseline to the last HCV-negative test or estimated date of seroconversion (midpoint between HCV-positive and the preceding HCV-negative test). Exposures: Episodes of prescription opioid use for noncancer pain were defined as acute (<90 days) or long-term (≥90 days). Prescription opioid exposure status (long-term vs prescription opioid-naive/acute) was treated as time-varying in survival analyses. In secondary analyses, long-term exposure was stratified by intensity of use (chronic vs. episodic) and by average daily dose in morphine equivalents (MEQ). Main Outcomes and Measures: Multivariable Cox regression models were used to assess the association between time-varying prescription opioid status and HCV seroconversion. Results: A total of 382 478 individuals who had more than 1 HCV test were included, of whom more than half were female (224 373 [58.7%]), born before 1974 (201 944 [52.8%]), and younger than 35 years at baseline (196 298 [53.9%]). Participants were followed up for 2 057 668 person-years and 1947 HCV seroconversions occurred. Of the participants, 41 755 people (10.9%) were exposed to long-term prescription opioid therapy at baseline or during follow-up. The HCV seroconversion rate per 1000 person-years was 0.8 among the individuals who were prescription opioid-naive/acute (1489 of 1947 [76.5%] seroconversions; 0.4% seroconverted within 5 years) and 2.1 with long-term prescription opioid therapy (458 of 1947 [23.5%] seroconversions; 1.1% seroconverted within 5 years). In multivariable analysis, exposure to long-term prescription opioid therapy was associated with a 3.2-fold (95% CI, 2.9-3.6) higher risk of HCV seroconversion (vs prescription opioid-naive/acute). In separate Cox models, long-term chronic use was associated with a 4.7-fold higher risk of HCV seroconversion (vs naive/acute use 95% CI, 3.9-5.8), and long-term higher-dose use (≥90 MEQ) was associated with a 5.1-fold higher risk (vs naive/acute use 95% CI, 3.7-7.1). Conclusions and Relevance: In this cohort study of people with more than 1 HCV test, long-term prescription opioid therapy for noncancer pain was associated with a higher risk of HCV seroconversion among individuals who were injection drug use-naive at baseline or at prescription opioid initiation. These results suggest injection drug use initiation risk is higher among people dispensed long-term therapy and may be useful for informing approaches to identify and prevent HCV infection. These findings should not be used to justify abrupt discontinuation of long-term therapy, which could increase risk of harms.

Prescription opioid treatment for non-cancer pain and initiation of injection drug use: large retrospective cohort study.

OBJECTIVE: To assess the association between long term prescription opioid treatment medically dispensed for non-cancer pain and the initiation of injection drug use (IDU) among individuals without a history of substance use. DESIGN: Retrospective cohort study. SETTING: Large administrative data source (containing information for about 1.7 million individuals tested for hepatitis C virus or HIV in British Columbia, Canada) with linkage to administrative health databases, including dispensations from community pharmacies. PARTICIPANTS: Individuals age 11-65 years and without a history of substance use (except alcohol) at baseline. MAIN OUTCOME MEASURES: Episodes of prescription opioid use for non-cancer pain were identified based on drugs dispensed between 2000 and 2015. Episodes were classified by the increasing length and intensity of opioid use (acute (lasting <90 episode days), episodic (lasting ≥90 episode days; with <90 days' drug supply and/or <50% episode intensity), and chronic (lasting ≥90 episode days; with ≥90 days' drug supply and ≥50% episode intensity)). People with a chronic episode were matched 1:1:1:1 on socioeconomic variables to those with episodic or acute episodes and to those who were opioid naive. IDU initiation was identified by a validated administrative algorithm with high specificity. Cox models weighted by inverse probability of treatment weights assessed the association between opioid use category (chronic, episodic, acute, opioid naive) and IDU initiation. RESULTS: 59 804 participants (14 951 people from each opioid use category) were included in the matched cohort, and followed for a median of 5.8 years. 1149 participants initiated IDU. Cumulative probability of IDU initiation at five years was highest for participants with chronic opioid use (4.0%), followed by those with episodic use (1.3%) and acute use (0.7%), and those who were opioid naive (0.4%). In the inverse probability of treatment weighted Cox model, risk of IDU initiation was 8.4 times higher for those with chronic opioid use versus those who were opioid naive (95% confidence interval 6.4 to 10.9). In a sensitivity analysis limited to individuals with a history of chronic pain, cumulative risk for those with chronic use (3.4% within five years) was lower than the primary results, but the relative risk was not (hazard ratio 9.7 (95% confidence interval 6.5 to 14.5)). IDU initiation was more frequent at higher opioid doses and younger ages. CONCLUSIONS: The rate of IDU initiation among individuals who received chronic prescription opioid treatment for non-cancer pain was infrequent overall (3-4% within five years) but about eight times higher than among opioid naive individuals. These findings could have implications for strategies to prevent IDU initiation, but should not be used as a reason to support involuntary tapering or discontinuation of long term prescription opioid treatment.

Adverse events related to bystander naloxone administration in cases of suspected opioid overdose in British Columbia: An observational study.

INTRODUCTION: Take-Home Naloxone programs have been introduced across North America in response to rising opioid overdose deaths. There is currently limited real-world data on bystander naloxone administration, overdose outcomes, and evidence related to adverse events following bystander naloxone administration. METHODS: The research team used descriptive statistics from Take-Home Naloxone administration forms. We explored reported demographic variables and adverse events among people who received by-stander administered naloxone in a suspected opioid overdose event between August 31, 2012 and December 31, 2018 in British Columbia. We examined and contextualized differences across years given policy, program and drug toxicity changes. We used multivariate logistic regression to examine whether an association exists between number of ampoules of naloxone administered and the odds that the recipient will experience withdrawal symptoms. RESULTS: A large majority (98.1%) of individuals who were administered naloxone survived their overdose and 69.2% had no or only mild withdrawal symptoms. Receiving three (Adjusted Odds Ratio (AOR) 1.64 (95% Confidence Interval (CI): 1.08-2.48)) or four or more (AOR 2.19 (95% CI: 1.32-3.62)) ampoules of naloxone was significantly associated with odds of moderate or severe withdrawal compared to receiving one ampoule of naloxone. CONCLUSIONS: This study provides evidence from thousands of bystander reversed opioid overdoses using Take-Home Naloxone kits in British Columbia, and suggests bystander-administered naloxone is safe and effective for opioid overdose reversal. Data suggests an emphasis on titration during bystander naloxone training in situations where the person experiencing overdose can be adequately ventilated may help avoid severe withdrawal symptoms. We identified a decreasing trend in the likelihood of moderate or severe withdrawal over the study period.

Socioeconomic factors and substances involved in poisoning-related emergency department visits in British Columbia, Canada. / Facteurs socioéconomiques et substances en cause dans les visites aux urgences liées à des intoxications en Colombie Britannique (Canada).

INTRODUCTION: Canada's opioid crisis has taken thousands of lives, increasing awareness of poisoning-related injuries as an important public health issue. However, in British Columbia (BC), where overdose mortality rates are the highest in Canada, studies have not yet identified which demographic populations most often visit emergency departments (ED) due to all poisonings, nor which substances are most commonly involved. The aim of this study was to explore these gaps, after developing a methodology for calculating ED visit rates in BC. METHODS: Poisoning-related ED visit rates during fiscal years 2012/13 to 2016/17, inclusive, were calculated by sex, age group, poisoning substance and socioeconomic status, using a novel methodology developed in this study. ED data were sourced from the National Ambulatory Care Reporting System and population data from Statistics Canada's 2016 (or 2011) census profiles. RESULTS: During the study period, there were an estimated 81 463 poisoning-related ED visits (351.2 per 100 000 population). Infants, toddlers, youth and those aged 20-64 years had elevated risks of poisoning-related ED visits. Rates were highest among those in neighbourhoods with the greatest material (607.8 per 100 000 population) or social (484.2 per 100 000 population) deprivation. Over time, narcotics and psychodysleptics became increasingly common poisoning agents, while alcohol remained problematic. CONCLUSION: A methodology for estimating ED visit rates in BC was developed and applied to determine poisoning-related ED visit rates among various demographic groups within BC. British Columbians most vulnerable to poisoning have been identified, emphasizing the need for efforts to limit drug overdoses and excessive alcohol intoxication to reduce rates of these preventable injuries.

Analyses of Child and Youth Self-Poisoning Hospitalizations by Substance and Socioeconomic Status.

Child and youth self-poisoning is a growing public health issue in many regions of the world, including British Columbia (BC), Canada, where 15-19-year-olds have the highest rates of self-poisoning hospitalizations compared with those of all other ages. The purpose of this study was to identify what substances children and youth commonly used to poison themselves in BC and how socioeconomic status may impact self-poisoning risk. Self-poisoning hospitalization rates among 10-14 and 15-19-year-olds from 1 April 2012 to 31 March 2020 were calculated by substance using ICD-10-CA codes X60-X69 and T36-T65, as well as by socioeconomic status using the Institut National de Santé Publique du Québec's Deprivation Index. Nonopioid analgesics, antipyretics, and antirheumatics were the most common substances involved, with rates of 27.6 and 74.3 per 100,000 population among 10-14 and 15-19-year-olds, respectively, followed by antiepileptic, sedative-hypnotic, antiparkinsonism, and psychotropic drugs, with rates of 20.2 and 68.1 per 100,000 population among 10-14 and 15-19-year-olds, respectively. In terms of socioeconomic status, rates were highest among 10-19-year-olds living in neighbourhoods with the fewest social connections (243.7 per 100,000 population). These findings can inform poisoning prevention strategies and relevant policies, thereby reducing the number of self-poisoning events among children and youth.

Crystal methamphetamine use in British Columbia, Canada: A cross-sectional study of people who access harm reduction services.

INTRODUCTION: Increased use of crystal methamphetamine ("crystal meth") has been observed across North America and international jurisdictions, including a notable increase in the presence of methamphetamines in illicit drug toxicity deaths in British Columbia (BC), Canada. We used data from a cross-sectional survey and urine toxicology screening to report the prevalence, correlates, and validity of self-reported crystal meth use among clients of harm reduction sites in BC. MATERIALS AND METHODS: Survey data were collected from 1,107 participants across 25 communities in BC, through the 2018 and 2019 Harm Reduction Client Survey. We described reported substance use and used a multivariate logistic regression model to characterize crystal meth use. Urine samples provided by a subset of participants were used to derive validity of self-reported three-day crystal meth use compared to urine toxicology screening. RESULTS: Excluding tobacco, crystal meth was the most frequently reported substance used in the past three days in 2018 and 2019 (59.7% and 71.7%, respectively). Smoking was the dominant route of administration for crystal meth, crack, heroin, and fentanyl. Multivariate analysis determined significantly higher odds of crystal meth use among those who used opioids (Adjusted Odds Ratio [AOR] = 3.13), cannabis (AOR = 2.10), and alcohol (1.41), and among those who were not regularly housed (AOR = 2.08) and unemployed (AOR = 1.75). Age ≥50 was inversely associated with crystal meth use (AOR = 0.63). Sensitivity of self-reported crystal meth use was 86%, specificity was 86%, positive predictive value was 96%, and negative predictive value was 65%. CONCLUSIONS: Crystal meth was the most commonly used substance among clients of harm reduction sites in BC in 2018 and 2019, and was frequently used concurrently with opioids. Comparison to urine samples demonstrated high validity of self-reported crystal meth use. Understanding evolving patterns of substance use will be imperative in tailoring harm reduction and substance use services for individuals that use crystal meth.

Cohort profile: development and characteristics of a retrospective cohort of individuals dispensed prescription opioids for non-cancer pain in British Columbia, Canada.

PURPOSE: Prescription opioids (POs) are widely prescribed for chronic non-cancer pain but are associated with several risks and limited long-term benefit. Large, linked data sources are needed to monitor their harmful effects. We developed and characterised a retrospective cohort of people dispensed POs. PARTICIPANTS: We used a large linked administrative database to create the Opioid Prescribing Evaluation and Research Activities cohort of individuals dispensed POs for non-cancer pain in British Columbia (BC), Canada (1996-2015). We created definitions to categorise episodes of PO use based on a review of the literature (acute, episodic, chronic), developed an algorithm for inferring clinical indication and assessed patterns of PO use across a range of characteristics. FINDINGS TO DATE: The current cohort includes 1.1 million individuals and 3.4 million PO episodes (estimated to capture 40%-50% of PO use in BC). The majority of episodes were acute (81%), with most prescribed for dental or surgical pain. Chronic use made up 3% of episodes but 88% of morphine equivalents (MEQ). Across the acute to episodic to chronic episode gradient, there was an increasing prevalence of higher potency POs (hydromorphone, oxycodone, fentanyl, morphine), long-acting formulations and chronic pain related indications (eg, back, neck, joint pain). Average daily dose (MEQ) was similar for acute/episodic but higher for chronic episodes. Approximately 7% of the cohort had a chronic episode and chronic pain was the characteristic most strongly associated with chronic PO use. Individuals initiating a chronic episode were also more likely to have higher social/material deprivation and previous experience with a mental health condition or a problem related to alcohol or opioid use. Overall, these findings suggest our episode definitions have face validity and also provide insight into characteristics of people initiating chronic PO therapy. FUTURE PLANS: The cohort will be refreshed every 2 years. Future analyses will explore the association between POs and adverse outcomes.

Death after emergency department visits for opioid overdose in British Columbia: a retrospective cohort analysis.

BACKGROUND: Visits to the emergency department are critical opportunities to engage individuals after an overdose. We sought to estimate and compare the 12-month mortality between persons with visits to the emergency department related to opioid overdose and those with non-overdose-related visits. METHODS: We conducted a retrospective cohort study using the Provincial Overdose Cohort, which contains data for patients in British Columbia who had an opioid-related overdose between 2015 and 2017, along with a 20% random sample of BC residents for comparison. We examined all nonfatal visits to the emergency department between Jan. 1, 2015, and Dec. 31, 2016, among persons aged 14 to 74 years and compared the 12-month mortality between those with overdose-related visits and those with non-overdose-related visits. We estimated the hazard ratio for death, with adjustment for age, sex, comorbidity and disposition (discharged or left against medical advice). RESULTS: We included 3593 persons with overdose-related visits and 216 453 with non-overdose-related visits to the emergency department. Those with overdose-related visits were younger, were predominantly male and had more mental health conditions. The 12-month crude mortality probability was 5.4% (95% confidence interval [CI] 4.7%-6.2%) in this group and 1.7% (95% CI 1.6%-1.8%) among those with non-overdose-related visits. After adjustment, for persons who were discharged, the 12-month mortality hazard was 3.5 (95% CI 3.0-4.2) times higher among those with overdose-related visits than those with non-overdose-related visits. For persons who left against medical advice, the mortality hazard was 7.1 (95% CI 4.0-12.5) times higher among those with opioid overdose. INTERPRETATION: Among persons with overdose-related visits to the emergency department, 12-month mortality was higher than among those with non-overdose-related visits. Overdose-related visits should prompt urgent evidence-based interventions (e.g., take-home naloxone kits, buprenorphine-naloxone induction) to prevent future deaths.

Predicting mortality from acetaminophen poisoning shortly after hospital presentation.

AIMS: Early identification of patients likely to die after acetaminophen (APAP) poisoning remains challenging. We sought to compare the sensitivity and time to fulfilment (latency) of established prognostic criteria. METHODS: Three physician toxicologists independently classified every in-hospital death associated with APAP overdose from eight large Canadian cities over three decades using the Relative Contribution to Fatality scale from the American Association of Poison Control Centres. The sensitivity and latency were calculated for each of the following criteria: King's College Hospital (KCH), Model for End Stage Liver Disease (MELD) ≥33, lactate ≥3.5 mmol/L, phosphate ≥1.2 mmol/L 48+ hours post-ingestion, as well as combinations thereof. RESULTS: A total of 162 in-hospital deaths were classified with respect to APAP as follows: 26 Undoubtedly, 40 Probably, 27 Contributory, 14 Probably not, 25 Clearly not, and 30 Unknown. Cases from the first three classes (combined into n = 93 "APAP deaths") typically presented with supratherapeutic APAP concentrations, hepatotoxicity, acidaemia, coagulopathy and/or encephalopathy, and began antidotal treatment a median of 12 hours (IQR 3.4-30 h) from the end of ingestion. Among all patients deemed "APAP deaths", meeting either KCH or lactate criteria demonstrated the highest sensitivity (94%; 95% CI 86-98%), and the shortest latency from hospital arrival to criterion fulfilment (median 4.2 h; IQR 1.0-16 h). In comparison, the MELD criterion demonstrated a substantially lower sensitivity (55%; 43-66%) and longer latency (52 h; 4.4-∞ h, where "∞" denotes death prior to criterion becoming positive). CONCLUSIONS: Meeting either KCH or serum lactate criteria identifies most patients who die from acetaminophen poisoning at or shortly after hospital presentation.

Comparison of rates of opioid withdrawal symptoms and reversal of opioid toxicity in patients treated with two naloxone dosing regimens: a retrospective cohort study.

INTRODUCTION: When managing opioid overdose (OD) patients, the optimal naloxone regimen should rapidly reverse respiratory depression while avoiding opioid withdrawal. Published naloxone administration guidelines have not been empirically validated and most were developed before fentanyl OD was common. In this study, rates of opioid withdrawal symptoms (OW) and reversal of opioid toxicity in patients treated with two naloxone dosing regimens were evaluated. METHODS: In this retrospective matched cohort study, health records of patients who experienced an opioid OD treated in two urban emergency departments (ED) during an ongoing fentanyl OD epidemic were reviewed. Definitions for OW and opioid reversal were developed a priori. Low dose naloxone (LDN; ≤0.15 mg) and high dose naloxone (HDN; >0.15 mg) patients were matched in a 1:4 ratio based upon initial respiratory rate (RR). The proportion of patients who developed OW and who met reversal criteria were compared between those treated initially with LDN or HDN. Odds ratios (OR) for OW and opioid reversal were obtained via logistic regression stratified by matched sets and adjusted for age, sex, pre-naloxone GCS, and presence of non-opioid drugs or alcohol. RESULTS: Eighty LDN patients were matched with 299 HDN patients. After adjustment, HDN patients were more likely than LDN patients to have OW after initial dose (OR = 8.43; 95%CI: 1.96, 36.3; p = 0.004) and after any dose (OR = 2.56; 95%CI: 1.17, 5.60; p = 0.019). HDN patients were more likely to meet reversal criteria after initial dose (OR = 2.73; 95%CI: 1.19, 6.26; p = 0.018) and after any dose (OR = 6.07; 95%CI: 1.81, 20.3; p = 0.003). CONCLUSIONS: HDN patients were more likely to have OW but also more likely to meet reversal criteria versus LDN patients.

Comparing mortality and healthcare utilization in the year following a paramedic-attended non-fatal overdose among people who were and were not transported to hospital: A prospective cohort study using linked administrative health data.

BACKGROUND: As the overdose emergency continues in British Columbia (BC), paramedic-attended overdoses are increasing, as is the proportion of people not transported to hospital following an overdose. This study investigated risk of death and subsequent healthcare utilization for people who were and were not transported to hospital after a paramedic-attended non-fatal overdose. METHODS: Using a linked administrative health data set which includes all overdoses that come into contact with health services in BC, we conducted a prospective cohort study of people who experienced a paramedic-attended non-fatal overdose between 2015 and 2016. People were followed for 365 days after the index event. The primary outcomes assessed were all-cause mortality and overdose-related death. Additionally, we examined healthcare utilization after the index event. RESULTS: In this study, 8659 (84%) people were transported and 1644 (16%) were not transported to hospital at the index overdose event. There were 279 overdose deaths (2.7% of people, 59.4% of deaths) during follow-up. There was no significant difference in risk of overdose-related death, though people not transported had higher odds of a subsequent non-fatal overdose event captured in emergency department and outpatient records within 90 days. People transported to hospital had higher odds of using hospital and outpatient services for any reason within 365 days. CONCLUSIONS: Transport to hospital after a non-fatal overdose is an opportunity to provide care for underlying and chronic conditions. There is a need to better understand factors that contribute to non-transport, particularly among people aged 20-59 and people without chronic conditions.

Naloxone dosing in the era of ultra-potent opioid overdoses: a systematic review.

OBJECTIVES: Evaluate the relationship between naloxone dose (initial and cumulative) and opioid toxicity reversal and adverse events in undifferentiated and presumed fentanyl/ultra-potent opioid overdoses. METHODS: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings (1972 to 2018). We included interventional, observational, and case studies/series reporting on naloxone dose and opioid toxicity reversal or adverse events in people >12 years old. RESULTS: A total of 174 studies (110 case reports/series, 57 observational, 7 interventional) with 26,660 subjects (median age 35 years; 74% male). Heterogeneity precluded meta-analysis. Where reported, we abstracted naloxone dose and proportion of patients with toxicity reversal. Among patients with presumed exposure to fentanyl/ultra-potent opioids, 56.9% (617/1,085) responded to an initial naloxone dose ≤0.4 mg compared with 80.2% (170/212) of heroin users, and 30.4% (7/23) responded to an initial naloxone dose >0.4 mg compared with 59.1% (1,434/2,428) of heroin users. Among patients who responded, median cumulative naloxone doses were higher for presumed fentanyl/ultra-potent opioids than heroin overdoses in North America, both before 2015 (fentanyl/ultra-potent opioids: 1.8 mg [interquartile interval {IQI}, 1.0, 4.0]; heroin: 0.8 mg [IQI, 0.4, 0.8]) and after 2015 (fentanyl/ultra-potent opioids: 3.4 mg [IQI, 3.0, 4.1]); heroin: 2 mg [IQI, 1.4, 2.0]). Where adverse events were reported, 11% (490/4,414) of subjects experienced withdrawal. Variable reporting, heterogeneity and poor-quality studies limit conclusions. CONCLUSIONS: Practitioners have used higher initial doses, and in some cases higher cumulative naloxone doses to reverse toxicity due to presumed fentanyl/ultra-potent opioid exposure compared with other opioids. High-quality comparative naloxone dosing studies assessing effectiveness and safety are needed.

Naloxone interventions in opioid overdoses: a systematic review protocol.

BACKGROUND: North America is in the midst of an unabated opioid overdose epidemic due to the increasing non-medical use of fentanyl and ultra-potent opioids. Naloxone is an effective antidote to opioid toxicity, yet its optimal dosing in the context of fentanyl and ultra-potent opioid overdoses remains unknown. This review aims to determine the relationship between the first empiric dose of naloxone and reversal of toxicity, adverse events, and the total cumulative dose required among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. Secondary objectives include evaluating the relationship between the cumulative naloxone dose and toxicity reversal and adverse events, among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. METHODS: To identify studies, we will search MEDLINE, Embase, CENTRAL, DARE, CDAG, CINAHL, Science Citation Index, multiple trial registries, and the gray literature. Included studies will evaluate patients with suspected or confirmed opioid toxicity from undifferentiated opioids and ultra-potent opioids, who received an empiric and possibly additional doses of naloxone. The main outcomes of interest are the relationship between naloxone dose and toxicity reversal and adverse events. We will include controlled and non-controlled interventional studies, observational studies, case reports/series, and reports from poison control centers. We will extract data and assess study quality in duplicate with discrepancies resolved by consensus or a third party. We will use the Downs and Black and Cochrane risk of bias tools for observational and randomized controlled studies. If we find sufficient variation in dose, we will fit a random effects one-stage model to estimate a dose-response relationship. We will conduct multiple subgroup analyses, including by type of opioid used and by suspected high and low prevalence of ultra-potent opioid use based on geographic location and time of the original studies. DISCUSSION: Our review will include the most up-to-date available data including ultra-potent opioids to inform the current response to the opioid epidemic, addressing the limitations of recent reviews. We anticipate limitations relating to study heterogeneity. We will disseminate study results widely to update overdose treatment guidelines and naloxone dosing in Take Home Naloxone programs.

Cannabis use as a risk factor for causing motor vehicle crashes: a prospective study.

AIM: We conducted a responsibility analysis to determine whether drivers injured in motor vehicle collisions who test positive for Δ-9-tetrahydrocannabinol (THC) or other drugs are more likely to have contributed to the crash than those who test negative. DESIGN: Prospective case-control study. SETTING: Trauma centres in British Columbia, Canada. PARTICIPANTS: Injured drivers who required blood tests for clinical purposes following a motor vehicle collision. MEASUREMENTS: Excess whole blood remaining after clinical use was obtained and broad-spectrum toxicology testing performed. The analysis quantified alcohol and THC and gave semiquantitative levels of other impairing drugs and medications. Police crash reports were analysed to determine which drivers contributed to the crash (responsible) and which were 'innocently involved' (non-responsible). We used unconditional logistic regression to determine the likelihood (odds ratio: OR) of crash responsibility in drivers with 0 < THC < 2 ng/ml, 2 ng/ml ≤ THC < 5 ng/ml and THC ≥ 5 ng/ml (all versus THC = 0 ng/ml). Risk estimates were adjusted for age, sex and presence of other impairing substances. FINDINGS: We obtained toxicology results on 3005 injured drivers and police reports on 2318. Alcohol was detected in 14.4% of drivers, THC in 8.3%, other drugs in 8.9% and sedating medications in 19.8%. There was no increased risk of crash responsibility in drivers with THC < 2 ng/ml or 2 ≤ THC < 5 ng/ml. In drivers with THC ≥ 5 ng/ml, the adjusted OR was 1.74 [95% confidence interval (CI) = 0.59-6.36; P = 0.35]. There was significantly increased risk of crash responsibility in drivers with blood alcohol concentration (BAC) ≥ 0.08% (OR = 6.00;95% CI = 3.87-9.75; P < 0.01), other recreational drugs detected (OR = 1.82;95% CI = 1.21-2.80; P < 0.01) or sedating medications detected (OR = 1.45; 95%CI = 1.11-1.91; P < 0.01). CONCLUSIONS: In this sample of non-fatally injured motor vehicle drivers in British Columbia, Canada, there was no evidence of increased crash risk in drivers with Δ-9-tetrahydrocannabinol < 5 ng/ml and a statistically non-significant increased risk of crash responsibility (odds ratio = 1.74) in drivers with Δ-9-tetrahydrocannabinol ≥ 5 ng/ml.