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Objectives. To determine whether the Communities That HEAL (CTH) intervention is effective in increasing naloxone distribution compared with usual care. Methods. The HEALing (Helping to End Addiction Long-Term) Communities Study (HCS) is a cluster-randomized, parallel-arm, wait-list controlled implementation science trial testing the impact of the CTH intervention on increasing the use of evidence-based practices to lower opioid-related overdose deaths. Communities (n = 67) highly impacted by opioid overdose in Kentucky, Massachusetts, New York, and Ohio were allocated to CTH intervention (n = 34) or wait-list comparison (usual care; n = 33) arms. The primary outcome for this study was the number of naloxone units distributed in HCS communities during the comparison period (July 1, 2021‒June 30, 2022), examined using an intent-to-treat negative binomial regression model. Results. Naloxone distribution was 79% higher in the CTH intervention versus usual care arm (adjusted relative rate = 1.79; 95% confidence interval = 1.28, 2.51; P = .001; adjusted rates of naloxone distribution 3378 vs 1884 naloxone units per 100 000 residents), when controlling for urban‒rural status, state, baseline opioid-related overdose death rate, and baseline naloxone distribution rate. Conclusions. The CTH intervention increased naloxone distribution compared with usual care in communities highly impacted by the opioid crisis. Trial Registration. ClinicalTrials.gov identifier: NCT04111939. ( Am J Public Health. 2025;115(1):83–94. https://doi.org/10.2105/AJPH.2024.307845 )

Most people addicted to opioids began taking them because they were legally prescribed. Little attention has been paid to changing physicians' prescribing behavior. Using a randomized controlled trial format, Doctor et al. monitored the effect of notifying physicians who had a patient die of opioid overdose within 12 months of a prescription. The physicians received an injunction to prescribe safely from their county's medical examiner. This intervention led to reductions in high-intensity prescribing, reductions in the likelihood that an opioid-naïve patient received a prescription, and a reduction in overall cumulative opioid intake. Science , this issue p. 588 Feedback about a patient’s overdose may instill safe opioid prescribing habits in physicians. Most opioid prescription deaths occur among people with common conditions for which prescribing risks outweigh benefits. General psychological insights offer an explanation: People may judge risk to be low without available personal experiences, may be less careful than expected when not observed, and may falter without an injunction from authority. To test these hypotheses, we conducted a randomized trial of 861 clinicians prescribing to 170 persons who subsequently suffered fatal overdoses. Clinicians in the intervention group received notification of their patients’ deaths and a safe prescribing injunction from their county’s medical examiner, whereas physicians in the control group did not. Milligram morphine equivalents in prescriptions filled by patients of letter recipients versus controls decreased by 9.7% (95% confidence interval: 6.2 to 13.2%; P < 0.001) over 3 months after intervention. We also observed both fewer opioid initiates and fewer high-dose opioid prescriptions by letter recipients.

How to mitigate the dramatic increase in the number of self-inflicted deaths from suicide, alcohol-related liver disease, and drug overdose among young adults has become a critical public health question. A promising area of study looks at interventions designed to address risk factors for the behaviors that precede these —often denoted—“deaths of despair.” This paper examines whether a childhood intervention can have persistent positive effects by reducing adolescent and young adulthood (age 25) behaviors that precede these deaths, including suicidal ideation, suicide attempts, hazardous drinking, and opioid use. These analyses test the impact and mechanisms of action of Fast Track (FT), a comprehensive childhood intervention designed to decrease aggression and delinquency in at-risk kindergarteners. We find that random assignment to FT significantly decreases the probability of exhibiting any behavior of despair in adolescence and young adulthood. In addition, the intervention decreases the probability of suicidal ideation and hazardous drinking in adolescence and young adulthood as well as opioid use in young adulthood. Additional analyses indicate that FT’s improvements to children’s interpersonal (e.g., prosocial behavior, authority acceptance), intrapersonal (e.g., emotional recognition and regulation, social problem solving), and academic skills in elementary and middle school partially mediate the intervention effect on adolescent and young adult behaviors of despair and self-destruction. FT’s improvements to interpersonal skills emerge as the strongest indirect pathway to reduce these harmful behaviors. This study provides evidence that childhood interventions designed to improve these skills can decrease the behaviors associated with premature mortality.

Background The HEALing Communities Study was a multi-site cluster randomized waitlist-controlled trial evaluating a community-engaged, data-driven intervention to select and deploy evidence-based practices (EBPs) including overdose education and naloxone distribution (OEND), medication for opioid use disorder (MOUD), and safer opioid prescribing. The trial was conducted in 67 highly impacted communities in 4 states, including 8 Rural and 8 urban communities in New York State (NYS). To inform future community-level decision making, we estimated the implementation costs of the EBPs selected by NYS communities. Methods The study was implemented between January 2020-June 2022 (Wave 1, 30 months duration including the peak COVID-19 emergency period) and July 2022-December 2023 (Wave 2, 18 months); each wave included 4 Rural and 4 urban NYS communities. We collected cost data prospectively using invoices, administrative records, and interviews with program staff and stakeholders. We then conducted a micro-costing analysis from the community perspective and compared costs from Waves 1 and 2. Results In both Waves, each community deployed on average 15 EBPs (range 8–25). EBP costs averaged $705,000 (range $320,000-$1.3 million) and $312,000 (range $39,200-$686,300) in Waves 1 and 2, respectively. In Wave 1, 25% of costs were allocated for OEND, 71% for MOUD, and 4% for safer prescribing, compared to 38% for OEND, 60% for MOUD, and 2% for safer prescribing in Wave 2. Average EBP costs per community were $147,600 (range $20,900-$374,000) for those in the OEND category, $345,400 (range $4,100-$1.1 million) for MOUD, and $16,400 (range $360-$105,500) for safer prescribing. Total EBP cost per capita in urban communities was $0.32 compared to $2.65 in Rural communities in Wave 1, and $0.41 urban communities compared to $0.65 in Rural communities in Wave 2. Conclusions The lower EBP costs in Wave 2 resulted from differences in EBP categories and specific EBPs selected and may also reflect differences in the duration of the intervention and the impact of the COVID-19 pandemic over time. Higher per capita costs in rural communities indicate that many costs were not directly related to the number of individuals served.

The naloxone investigation (N-ALIVE) randomized trial commenced in the UK in May 2012, with the preliminary phase involving 5,600 prisoners on release. The trial is investigating whether heroin overdose deaths post-prison release can be prevented by prior provision of a take-home emergency supply of naloxone. Heroin contributes disproportionately to drug deaths through opiate-induced respiratory depression. Take-home emergency naloxone is a novel preventive measure for which there have been encouraging preliminary reports from community schemes. Overdoses are usually witnessed, and drug users themselves and also family members are a vast intervention workforce who are willing to intervene, but whose responses are currently often inefficient or wrong. Approximately 10% of provided emergency naloxone is thought to be used in subsequent emergency resuscitation but, as yet, there have been no definitive studies. The period following release from prison is a time of extraordinarily high mortality, with heroin overdose deaths increased more than sevenfold in the first fortnight after release. Of prisoners with a previous history of heroin injecting who are released from prison, 1 in 200 will die of a heroin overdose within the first 4 weeks. There are major scientific and logistical challenges to assessing the impact of take-home naloxone. Even in recently released prisoners, heroin overdose death is a relatively rare event: hence, large numbers of prisoners need to enter the trial to assess whether take-home naloxone significantly reduces the overdose death rate. The commencement of pilot phase of the N-ALIVE trial is a significant step forward, with prisoners being randomly assigned either to treatment-as-usual or to treatment-as-usual plus a supply of take-home emergency naloxone. The subsequent full N-ALIVE trial (contingent on a successful pilot) will involve 56,000 prisoners on release, and will give a definitive conclusion on lives saved in real-world application. Advocates call for implementation, while naysayers raise concerns. The issue does not need more public debate; it needs good science.

Causal inference for treatments with many versions requires a careful specification of the versions of treatment. Specifically, the existence of multiple relevant versions of treatment has implications for the selection of confounders. To illustrate this, we estimate the effect of organ transplantation using grafts from donors who died due to anoxic drug overdose, on recipient graft survival in the US. We describe how explicitly outlining the target trial (i.e. the hypothetical randomized trial which would answer the causal question of interest) to be emulated by an observational study analysis helps conceptualize treatment versions, guides selection of appropriate adjustment variables, and helps clarify the settings in which causal effects of compound treatments will be of value to decision-makers.

There is a developing drug epidemic in the United States. Jalal et al. analyzed nearly 600,000 unintentional drug overdoses over a 38-year period. Although the overall mortality rate closely followed an exponential growth curve, the pattern itself is a composite of several underlying subepidemics of different drugs. Geographic hotspots have developed over time, as well as drug-specific demographic differences. Science , this issue p. eaau1184 The drug overdose epidemic in the United States is a composite of drug-specific subepidemics. Better understanding of the dynamics of the current U.S. overdose epidemic may aid in the development of more effective prevention and control strategies. We analyzed records of 599,255 deaths from 1979 through 2016 from the National Vital Statistics System in which accidental drug poisoning was identified as the main cause of death. By examining all available data on accidental poisoning deaths back to 1979 and showing that the overall 38-year curve is exponential, we provide evidence that the current wave of opioid overdose deaths (due to prescription opioids, heroin, and fentanyl) may just be the latest manifestation of a more fundamental longer-term process. The 38+ year smooth exponential curve of total U.S. annual accidental drug poisoning deaths is a composite of multiple distinctive subepidemics of different drugs (primarily prescription opioids, heroin, methadone, synthetic opioids, cocaine, and methamphetamine), each with its own specific demographic and geographic characteristics.

Objectives. We examined the causes of hospitalization and death of people who inject drugs participating in the Bangkok Tenofovir Study, an HIV preexposure prophylaxis trial. Methods. The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial conducted during 2005 to 2012 among 2413 people who inject drugs. We reviewed medical records to define the causes of hospitalization and death, examined participant characteristics and risk behaviors to determine predictors of death, and compared the participant mortality rate with the rate of the general population of Bangkok, Thailand. Results. Participants were followed an average of 4 years; 107 died: 22 (20.6%) from overdose, 13 (12.2%) from traffic accidents, and 12 (11.2%) from sepsis. In multivariable analysis, older age (40–59 years; P = .001), injecting drugs (P = .03), and injecting midazolam (P < .001) were associated with death. The standardized mortality ratio was 2.9. Conclusions. People who injected drugs were nearly 3 times as likely to die as were those in the general population of Bangkok and injecting midazolam was independently associated with death. Drug overdose and traffic accidents were the most common causes of death, and their prevention should be public health priorities.

The increases were strongly correlated with increases in synthetic opioid deaths but not with pharmaceutical fentanyl prescribing rates, suggesting that the increases were largely due to IMF.3 In a recent report, fentanyl was detected in at least half of the opioid overdose deaths from July to December 2016 in 7 of the 10 states examined.4 Traditionally, the Centers for Disease Control and Prevention (CDC) and others have included synthetic opioid deaths in estimates of \"prescription\" opioid deaths. Only 4.9% bought opioids from a drug dealer or stranger, and 5.6% reported obtaining them by stealing from a doctor's office, clinic, hospital, or pharmacy or in some other way.5 The National Vital Statistics System (NVSS) multiple causeof-death mortality files record drug overdose deaths, which are identified with the International Classification of Diseases, 10th Revision (1CD-10; Geneva, Switzerland: World Health Organization; 1992), according to the underlying cause-of-death codes X40 to X44 (unintentional), X60 to X64 (suicide), X85 (homicide), or Y10 to Y14 (undetermined intent). Death rates under both measures remain alarmingly high. Because of the increasing evidence that deaths involving synthetic opioids are likely a result of IMF, this more conservative approach likely provides a relatively more accurate number of prescription opioid- involved deaths, even though it excludes synthetic opioids that may have been pharmaceutically manufactured and prescribed. Advances in surveillance, such as the CDC National Center for Injury Prevention and Control's State Unintentional Drug Overdose Reporting System, which currently funds 32 states and Washington, DC, allow for data abstraction from preliminary death certificates and medical examiner or coroner reports on unintentional and undetermined opioid overdose deaths, with detailed data from death scene investigations and toxicology testing.