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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.).

Background Naloxone is the usual drug used in opioid-induced respiratory depression but it has a short half-life, precipitates withdrawal in dependent patients, and thus for persistent reversal of long-acting opioids has to be given by titrated doses and infusions. The partial agonist buprenorphine has a much longer duration of action and causes less severe withdrawal, but still should largely reverse respiratory depression induced by full agonist opioids. We aimed to compare the efficacy/safety of buprenorphine and naloxone in reversing respiratory depression in methadone-poisoned opioid-dependent patients. Methods Patients with methadone-induced respiratory depression were randomized to receive naloxone (titrated doses), or lower or higher doses of buprenorphine (10 μg/kg or 15 μg/kg). The primary outcome was immediate reversal of respiratory depression. We also recorded acute opioid withdrawal, need for intubation/recurrent apnea, repeated doses of opioid antagonists, length of hospital stay, other morbidity, and mortality. The study was registered with the Iranian Registry of Clinical Trials (Trial ID: 18265; Approval code: IRCT2015011020624N1). Results Eighty-five patients were randomized; 55/56 patients who received buprenorphine had rapid reversal of respiratory depression, which persisted for at least 12 h. Naloxone was effective in 28/29 patients, but often required very high titrated doses (thus delaying time to respond) and prolonged infusions. Intubation (8/29 vs 5/56) and opioid withdrawal (15/29 vs 7/56) were less common with buprenorphine. There were no serious complications or deaths in those receiving buprenorphine. The 15-μg/kg buprenorphine dose appeared to provide a longer duration of action, but precipitated withdrawal more frequently than the 10-μg/kg dose. Conclusion Buprenorphine appears to be a safe and effective substitute for naloxone in overdosed opioid-dependent patients. Further studies are warranted to explore the optimal dosing strategy for buprenorphine to consistently maintain reversal of respiratory depression but not precipitate withdrawal. Trial registration number IRCT2015011020624N1 . Registered 30 September 2015.

BackgroundOpioid overdose is a major and increasing cause of injury and death. There is an urgent need for interventions to reduce overdose events among high-risk persons.MethodsAdults at elevated risk for opioid overdose involving heroin or pharmaceutical opioids who had been cared for in an emergency department (ED) were randomised to overdose education combined with a brief behavioural intervention and take-home naloxone or usual care. Outcomes included: (1) time to first opioid overdose-related event resulting in medical attention or death using competing risks survival analysis; and (2) ED visit and hospitalisation rates, using negative binomial regression and adjusting for time at risk.ResultsDuring the follow-up period, 24% of the 241 participants had at least one overdose event, 85% had one or more ED visits and 55% had at least one hospitalisation, with no significant differences between intervention and comparison groups. The instantaneous risk of an overdose event was not significantly lower for the intervention group (sub-HR: 0.83; 95% CI 0.49 to 1.40).DiscussionThese null findings may be due in part to the severity of the population in terms of housing insecurity (70% impermanently housed), drug use, unemployment and acute healthcare issues. Given the high overdose and healthcare utilisation rates, more intensive interventions, such as direct referral and provision of housing and opioid agonist treatment medications, may be necessary to have a substantial impact on opioid overdoses for this high-acuity population in acute care settings.Trial registration numberNCT0178830; Results.

BackgroundAdolescents and young adults with risk factors for opioid misuse and opioid use disorder are at elevated risk for overdose. We examined prior non-fatal overdose experiences among at-risk adolescents/young adults to inform prevention efforts.MethodsAdolescents/young adults (ages 16–30) in two US emergency departments self-reporting past year opioid misuse or opioid use plus a misuse risk factor completed a baseline survey as part of an ongoing randomised controlled trial. We describe baseline factors associated with (a) overall non-fatal overdose experiences and (b) groups based on substance(s) used during the worst overdose experience.ResultsAmong 771 participants (27.9% male), 40.7% reported a non-fatal overdose experience. Compared with those without a prior overdose experience, those with prior overdose experience(s) were less likely to be heterosexual, and more likely to report a prior suicide attempt and greater peer substance misuse. Regarding the worst overdose experience, substance(s) included: 36.6% alcohol only, 28.0% alcohol and cannabis, 22.6% alcohol with other substance(s) and 12.7% other substance(s) only (eg, opioids). Compared with the alcohol only group, the alcohol and cannabis group were younger and less likely to be heterosexual; the alcohol with other substance(s) group were older and had greater peer substance misuse; and the other substance(s) only group were more likely to be male, receive public assistance, screen positive for anxiety and less likely to be heterosexual.ConclusionsAmong at-risk adolescents/young adults, findings support the need for tailored overdose prevention efforts based on substance(s) used, with consideration of sexuality, mental health and peer substance use.Trial registration number NCT04550715.

We summarise the evidence for medicinal uses of opioids, harms related to the extramedical use of, and dependence on, these drugs, and a wide range of interventions used to address these harms. The Global Burden of Diseases, Injuries, and Risk Factors Study estimated that in 2017, 40·5 million people were dependent on opioids (95% uncertainty interval 34·3–47·9 million) and 109 500 people (105 800–113 600) died from opioid overdose. Opioid agonist treatment (OAT) can be highly effective in reducing illicit opioid use and improving multiple health and social outcomes—eg, by reducing overall mortality and key causes of death, including overdose, suicide, HIV, hepatitis C virus, and other injuries. Mathematical modelling suggests that scaling up the use of OAT and retaining people in treatment, including in prison, could avert a median of 7·7% of deaths in Kentucky, 10·7% in Kiev, and 25·9% in Tehran over 20 years (compared with no OAT), with the greater effects in Tehran and Kiev being due to reductions in HIV mortality, given the higher prevalence of HIV among people who inject drugs in those settings. Other interventions have varied evidence for effectiveness and patient acceptability, and typically affect a narrower set of outcomes than OAT does. Other effective interventions focus on preventing harm related to opioids. Despite strong evidence for the effectiveness of a range of interventions to improve the health and wellbeing of people who are dependent on opioids, coverage is low, even in high-income countries. Treatment quality might be less than desirable, and considerable harm might be caused to individuals, society, and the economy by the criminalisation of extramedical opioid use and dependence. Alternative policy frameworks are recommended that adopt an approach based on human rights and public health, do not make drug use a criminal behaviour, and seek to reduce drug-related harm at the population level.

To determine pharmacy students’ knowledge retention from and comfort level with a patient-case simulation compared with a written patient case. Pharmacy students were randomly assigned to participate in either a written patient case or a simulated patient case in which a high-fidelity mannequin was used to portray a patient experiencing a narcotic and acetaminophen overdose. Participants’ responses on a multiple-choice test and a survey instrument administered before the case, immediately after the case, and 25 days later indicated that participation in the simulated patient case did not result in greater knowledge retention or comfort level than participation in the written patient case. Students’ knowledge improved post-intervention regardless of which teaching method was used. Although further research is needed to determine whether the use of simulation in the PharmD curriculum is equivalent or superior to other teaching methods, students’ enthusiasm for learning in a simulated environment where they can safely apply patient care skills make this technology worth exploring.

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 . . .

The rate of opioid analgesic overdose is proportional to the number of opioid prescriptions and the dose prescribed. This review considers the epidemiology, mechanisms, and management of opioid analgesic overdose. Opioid analgesic overdose is a preventable and potentially lethal condition that results from prescribing practices, inadequate understanding on the patient's part of the risks of medication misuse, errors in drug administration, and pharmaceutical abuse. 1 , 2 Three features are key to an understanding of opioid analgesic toxicity. First, opioid analgesic overdose can have life-threatening toxic effects in multiple organ systems. Second, normal pharmacokinetic properties are often disrupted during an overdose and can prolong intoxication dramatically. 3 Third, the duration of action varies among opioid formulations, and failure to recognize such variations can lead to inappropriate treatment decisions, sometimes with lethal results. 2 , . . .

To describe the use and efficacy of nebulized naloxone in patients with suspected opioid intoxication. This was an observational study conducted at an inner city emergency department. Patients were eligible if they had self-reported or suspected opioid intoxication and a spontaneous respiratory rate ≥6 breaths/minute. Nebulized naloxone (2 mg in 3 mL normal saline) was administered through a standard face mask at the discretion of the treating physician. Structured data collection included demographics, vital signs pre and post naloxone administration and adverse events. The primary outcome was level of consciousness, which was recorded pre and 15 minutes postnaloxone administration using the Glasgow Coma Scale (GCS) and the Richmond Agitation Sedation Scale (RASS). Of the 73 patients who presented with suspected opioid intoxication and were given naloxone over the study period, 26 were initially treated with nebulized naloxone. After nebulized naloxone administration, median GCS improved from 11 [interquartile range (IQR) 3.5] to 13 (IQR, 2.5), P = .001. Median RASS improved from −3.0 (IQR, −1.0) to −2.0 (IQR, −1.5), P < .0001. Need for supplemental oxygen decreased from 81% to 50%, P = .03. Vital signs did not differ pre/post therapy. There were few adverse effects from nebulized naloxone administration: 12% experienced moderate-severe agitation, 8% were diaphoretic and none vomited. Eleven required subsequent administrations of naloxone, nine of whom self-reported using either heroin, methadone or both. Of these, 5 underwent urine drug screening and all 5 tested positive for either opiates or methadone. Nebulized naloxone was well-tolerated and led to a reduction in the need for supplemental oxygen as well as improved median GCS and RASS scores in patients with suspected opioid intoxication.

Objective To evaluate the impact of state supported overdose education and nasal naloxone distribution (OEND) programs on rates of opioid related death from overdose and acute care utilization in Massachusetts.Design Interrupted time series analysis of opioid related overdose death and acute care utilization rates from 2002 to 2009 comparing community-year strata with high and low rates of OEND implementation to those with no implementation.Setting 19 Massachusetts communities (geographically distinct cities and towns) with at least five fatal opioid overdoses in each of the years 2004 to 2006.Participants OEND was implemented among opioid users at risk for overdose, social service agency staff, family, and friends of opioid users. Intervention OEND programs equipped people at risk for overdose and bystanders with nasal naloxone rescue kits and trained them how to prevent, recognize, and respond to an overdose by engaging emergency medical services, providing rescue breathing, and delivering naloxone.Main outcome measures Adjusted rate ratios for annual deaths related to opioid overdose and utilization of acute care hospitals.Results Among these communities, OEND programs trained 2912 potential bystanders who reported 327 rescues. Both community-year strata with 1-100 enrollments per 100 000 population (adjusted rate ratio 0.73, 95% confidence interval 0.57 to 0.91) and community-year strata with greater than 100 enrollments per 100 000 population (0.54, 0.39 to 0.76) had significantly reduced adjusted rate ratios compared with communities with no implementation. Differences in rates of acute care hospital utilization were not significant.Conclusions Opioid overdose death rates were reduced in communities where OEND was implemented. This study provides observational evidence that by training potential bystanders to prevent, recognize, and respond to opioid overdoses, OEND is an effective intervention.