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Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices. In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults. During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year. In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).

Governments can address widespread fentanyl-related deaths by pursuing a harm-reduction approach involving increased transparency for users and public health and public safety organizations, harm-reduction policing, expanded naloxone use, and targeted treatment. Fentanyl, a powerful synthetic opioid, poses an increasing public health threat. Low production costs encourage suppliers to “cut” heroin with the drug, particularly white powder heroin sold in the eastern United States. 1 Fentanyl also appears as a prevalent active ingredient in counterfeit OxyContin (oxycodone) tablets. The result is that fentanyl plays a major role in rising mortality due to heroin or opioid overdose. It poses a serious overdose risk because it can rapidly suppress respiration and cause death more quickly than do other opioids. From 2012 through 2014, the number of reported deaths involving fentanyl more than doubled, from 2628 . . .

This review provides a national summary of what is currently known about the Canadian opioid crisis with respect to opioid-related deaths and harms and potential risk factors as of December 2017. We reviewed all public-facing opioid-related surveillance or epidemiological reports published by provincial and territorial ministries of health and chief coroners' or medical examiners' offices. In addition, we reviewed publications from federal partners and reports and articles published prior to December 2017. We synthesized the evidence by comparing provincial and territorial opioid-related mortality and morbidity rates with the national rates to look for regional trends. The opioid crisis has affected every region of the country, although some jurisdictions have been impacted more than others. As of 2016, apparent opioid-related deaths and hospitalization rates were highest in the western provinces of British Columbia and Alberta and in both Yukon and the Northwest Territories. Nationally, most apparent opioid-related deaths occurred among males; individuals between 30 and 39 years of age accounted for the greatest proportion. Current evidence suggests regional age and sex differences with respect to health outcomes, especially when synthetic opioids are involved. However, differences between data collection methods and reporting requirements may impact the interpretation and comparability of reported data. This report identifies gaps in evidence and areas for further investigation to improve our understanding of the national opioid crisis. The Public Health Agency of Canada will continue to work closely with the provinces, territories and national partners to further refine and standardize national data collection, conduct special studies and expand information-sharing to improve the evidence needed to inform public health action and prevent opioid-related deaths and harms.

Background British Columbia, Canada, is experiencing a public health emergency related to opioid overdoses driven by consumption of street drugs contaminated with illicitly manufactured fentanyl. This cross-sectional study evaluates a drug checking intervention for the clients of a supervised injection facility (SIF) in Vancouver. Methods Insite is a facility offering supervised injection services in Vancouver’s Downtown East Side, a community with high levels of injection drug use and associated harms, including overdose deaths. During July 7, 2016, to June 21, 2017, Insite clients were offered an opportunity to check their drugs for fentanyl using a test strip designed to test urine for fentanyl. Results of the drug check were recorded along with information including the substance checked, whether the client intended to dispose of the drug or reduce the dose and whether they experienced an overdose. Logistic regression models were constructed to assess the associations between drug checking results and dose reduction or drug disposal. Crude odds ratios (OR) and 95% confidence intervals (CI) were reported. Results About 1% of the visits to Insite during the study resulted in a drug check. Out of 1411 drug checks conducted by clients, 1121 (79.8%) were positive for fentanyl. Although most tests were conducted post-consumption, following a positive pre-consumption drug check, 36.3% ( n  = 142) of participants reported planning to reduce their drug dose while only 11.4% ( n  = 50) planned to dispose of their drug. While the odds of intended dose reduction among those with a positive drug check was significantly higher than those with a negative result (OR = 9.36; 95% CI 4.25–20.65), no association was observed between drug check results and intended drug disposal (OR = 1.60; 95% CI 0.79–3.26). Among all participants, intended dose reduction was associated with significantly lower odds of overdose (OR = 0.41; 95% CI 0.18–0.89). Conclusions Although only a small proportion of visits resulted in a drug check, a high proportion (~ 80%) of the drugs checked were contaminated with fentanyl. Drug checking at harm reduction facilities such as SIFs might be a feasible intervention that could contribute to preventing overdoses in the context of the current overdose emergency.

Novel synthetic opioids (NSOs) represent an emerging group of novel psychoactive substances, acting as agonists at the opioid receptors. NSOs include fentanyl-related compounds, e.g. methoxyacetylfentanyl (MeACF), and non-fentanyl analogs, e.g. “U compounds” including U-47700. Here we present three cases of death involving MeACF and U-47700, with particular reference to preliminary data on pharmacokinetics and tissue distribution.After a complete post-mortem examination, general unknown screenings and analysis of drugs of abuse were performed on postmortem samples by immunoassays, gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry. To quantify the analytes of interest in post-mortem blood and tissues, the standard addition method was used. A toxicological significance score (TSS), weighing the role of the NSO in each death case, was assigned.Case 1 died at the hospital after consumption of U-47700, methadone (serum levels: 2,600 ng/ml and 37 ng/ml), tilidine and benzodiazepines. In case 2, U-47700 (204 ng/ml) together with methadone (290 ng/ml), flubromazepam (480 ng/ml) and diazepam (300 ng/ml) were detected in peripheral blood. In case 3, methoxyacetylfentanyl (266 ng/ml), furanylfentanyl (4.3 ng/ml) 4-ANPP (15 ng/ml) and alprazolam (69 ng/ml) were quantified in femoral blood. In all cases, the NSO likely contributed to the death (TSS = 3).NSOs appear to be often consumed in the setting of polydrug intoxications, especially in combination with other opioids and benzodiazepines, which often exert synergistic effects. The standard addition method remains the most reliable in post-mortem analysis and toxicological results should always be evaluated together with circumstantial and autopsy data.

Drug-overdose deaths increased from 2016 through 2021 and were driven primarily by out-of-hospital deaths associated with fentanyl, which increased by 282% (from 46.6 per million to 178.0 per million).

•Acrylfentanyl caused 40 fatal intoxications in Sweden between April and October 2016.•Non-fatal acrylfentanyl intoxications occurred in lower number.•Acrylfentanyl and other new fentanyl-analogs keep appearing on the drug market. The European Nordic Countries are the most exposed to opioid-related deaths. Between April and October 2016, a series of forty lethal intoxications occurred in Sweden, in which the presence of the synthetic opioid acrylfentanyl was determined to be the main – or a contributing – cause of death. In the reported cases, the blood concentration of acrylfentanyl – mostly detected in combination with other drugs – ranged from 0.01ng/g to 5ng/g; victims were predominantly males (34 males and 6 females), and their age varied between 18 and 53 years. We further describe five cases, representative of the different drug administration route (nasal spray, tablets) and intentions (accidental or voluntary intoxication). Moreover, we address nine cases of non-lethal intoxication, in single (8 cases) or polydrug scenario (1 case). We discuss the present characteristics of the Swedish drug market for fentanyl-analogs in general and acrylfentanyl in particular, reporting a structural difficulty to effectively counteracting the appearance of unscheduled substances due to the constant turnover of new molecules on the recreational drug market.

•A fatal “bath salts” poisoning case, involving acetyl fentanyl and 4-methoxy PV-8.•Simultaneous quantitative analysis of both drugs was done using LC–MS/MS.•Administration of the drugs was most likely to be intravenous. A man in his 30’s was found at home, not breathing. He was admitted to an emergency hospital and the doctor confirmed his death. He had a history of methamphetamine abuse spanning several years, and while fresh needle marks were visible on his arm, the only other autopsy findings indicated an acute death. A small plastic bag containing a pale brown white powder, and a small amount of liquid in a syringe were found at the scene. The police forensic laboratory detected acetyl fentanyl and 4-methoxy PV8 (4-methoxy PHPP) in both the powder and the liquid. Scan analysis by gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) identified acetyl fentanyl and 4-methoxy PV8 in the urine sample. Both drugs were quantitated simultaneously by liquid chromatography–tandem mass spectrometry (LC–MS/MS), using the selected reaction monitoring method. The concentration of acetyl fentanyl in the femoral vein blood, urine, and gastric contents were 153, 240, and 880ng/mL respectively, and the concentration of 4-methoxy PV8 in the femoral vein blood, urine, and gastric contents were 389, 245, and 500ng/mL respectively. Cause of death was attributed to acute poisoning by “bath salts” containing acetyl fentanyl and 4-methoxy PV8. Evidence indicated that self-administered intravenous injection was the most likely scenario, and that the deceased had been a habitual user of the “bath salt” drug for some time. Drugs detected in the gastric contents could be explained by the gastric secretion of basic drugs, or drug-containing bile entering the gastric contents.

Background: In the last decade there has been a progressive increase in the use of new psychoactive substances (NPSs) that are not yet under international control. In particular, novel synthetic opioids (NSOs) have reappeared on the recreational drug market in the last few years. As a result, the use of NSOs has increased rapidly. This poses an emerging and demanding challenge to public health. Aim: To raise awareness among clinicians and other professionals about NPSs, especially NSOs, to summarize current knowledge about pharmacological properties, forms of NSO on the market, pattern of use, effects and consequences of use. Methods: An electronic search was carried out on the Medline/PubMed and Google Scholar databases to find selected search terms. Results: Some NPSs are already controlled, while others can be legally sold directly on the drug market (mainly via internet, less so by drug dealers) or be used as precursors for the synthesis of other designer drugs that mimic the psychoactive effects of controlled substances. Potential side-effects of NSOs include miosis, sedation, respiratory depression, hypothermia, inhibition of gastrointestinal propulsion, death (from opioid overdose). Conclusions: The severity of the opioid crisis has intensified with the introduction of highly potent NSOs on the drug market. As long as addicts are dying from overdose or similar causes, there is something more constructive to do than waiting for addicts to overdose on heroin at a place located near a remedy, as if to say, within reach of naloxone.

After remaining stable from 2010 to 2014, the rate of cocaine-involved overdose death increased sharply from 2015 to 2016. This study aims to determine the contribution of opioids, and fentanyl in particular, to the increase in cocaine-involved overdose death from 2015 to 2016. Using New York City death certificate data linked to medical examiner toxicology data, we identified all overdose deaths where post-mortem toxicology results were positive for cocaine from 2010 to 2016. We analyzed cocaine-involved overdose deaths by co-occurring substances. Age-adjusted rates per 100,000 residents were calculated for 6-month intervals from 2010 to 2016. Data suggest that increased deaths involving opioids, specifically fentanyl, accounted for most of the increase in cocaine-involved deaths from 2015 to 2016.