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Importance: The US is experiencing a protracted drug overdose crisis primarily associated with exposure to illicitly manufactured fentanyl (IMF), methamphetamine, and cocaine. Overdose risk and treatment responses may be directly affected by absolute drug exposure concentrations and drug use prevalence., Objective: To quantify changes in absolute drug exposure concentrations from 2013 to 2023., Design, Setting, and Participants: This cross-sectional study analyzed urine drug testing (UDT) results from urine specimens collected between January 1, 2013, and August 22, 2023, in 49 states and the District of Columbia. Urine specimens were obtained from patients aged 18 years or older who presented to substance use disorder treatment clinics. The UDT was ordered by clinicians based on medical necessity., Exposures: Urine specimens were analyzed for the following drugs or metabolites (analytes tested in parentheses): fentanyl (fentanyl), heroin (6-monoacetylmorphine), cocaine (benzoylecgonine), and methamphetamine (methamphetamine) using liquid chromatography with tandem mass spectrometry., Main Outcomes and Measures: Relative concentrations of fentanyl, heroin, cocaine, and methamphetamine. Creatinine-normalized drug concentration values were log-transformed prior to visualization and statistical analyses. The Mann-Kendall trend test was performed to examine trends over time. To estimate the geospatial and temporal patterns of drug concentration, a second series of models (1 for each drug) with an interaction effect for clinic location and collection year were fit., Results: A total of 921 931 unique UDT samples were collected from patients (549 042 males [59.6%]; median [IQR] age, 34 [27-44] years). The adjusted fentanyl concentration in urine specimens was 38.23 (95% CI, 35.93-40.67) ng/mg creatinine in 2023 and 4.61 (95% CI, 3.59-5.91) ng/mg creatinine in 2013. The adjusted methamphetamine concentration was 3461.59 (95% CI, 3271.88-3662.30) ng/mg creatinine in 2023 and 665.27 (95% CI, 608.51-727.32) ng/mg creatinine in 2013. The adjusted cocaine concentration was 1122.23 (95% CI, 1032.41-1219.87) ng/mg creatinine in 2023 and 559.71 (95% CI, 524.69-597.06) ng/mg creatinine in 2013. The adjusted heroin concentration was 58.36 (95% CI, 48.26-70.58) ng/mg creatinine in 2023 and 146.59 (95% CI, 136.06-157.92) ng/mg creatinine in 2013. Drug concentrations varied across US Census divisions., Conclusions and Relevance: This cross-sectional study found that absolute concentrations of fentanyl, methamphetamine, and cocaine in urine specimens increased from 2013 to 2023, with a decrease in heroin concentration during that period. The findings suggest that exposure to these substances, as well as the illicit drug supply, has fundamentally changed in many parts of the US, highlighting the need to reinforce surveillance initiatives and accelerate efforts to treat individuals with IMF and/or stimulant exposure.

Importance: Youth (those aged <18 years) parental death has been associated with negative health outcomes. Understanding the burden of parental death due to drug poisoning (herein, drugs) and firearms is essential for informing interventions., Objective: To estimate the incidence of youth parental death due to drugs, firearms, and all other causes., Design, Setting, and Participants: This cross-sectional observational study was conducted using vital registration, including all US decedents, and census data from January 1990 through December 2020. Data were analyzed from May 30, 2023, to March 28, 2024., Exposures: Parental death due to drug poisoning or firearms., Main Outcomes and Measures: A demographic matrix projection model was used to estimate the number and incidence of youth experiencing parental death, defined as the death of 1 or more parents, per 1000 population aged less than 18 years. Analyses evaluated parental deaths by drugs, firearms, and all other causes from 1999 through 2020 by race and ethnicity., Results: Between 1999 and 2020, there were 931 785 drug poisoning deaths and 736 779 firearm-related deaths with a mean (SD) age of 42.6 (16.3) years. Most deaths occurred among males (73.8%) and White decedents (70.8%) followed by Black (17.5%) and Hispanic (9.5%) decedents. An estimated 759 000 (95% CI, 722 000-800 000) youth experienced parental death due to drugs and an estimated 434 000 (95% CI, 409 000-460 000) youth experienced parental death due to firearms, accounting for 17% of all parental deaths. From 1999 to 2020, the estimated number of youth who experienced parental death increased 345% (95% CI, 334%-361%) due to drugs and 39% (95% CI, 37%-41%) due to firearms compared with 24% (95% CI, 23%-25%) due to all other causes. Black youth experienced a disproportionate burden of parental deaths, based primarily on firearm deaths among fathers. In 2020, drugs and firearms accounted for 23% of all parental deaths, double the proportion in 1999 (12%)., Conclusions and Relevance: Results of this modeling study suggest that US youth are at high and increasing risk of experiencing parental death by drugs or firearms. Efforts to stem this problem should prioritize averting drug overdoses and firearm violence, especially among structurally marginalized groups.

Importance: Since 1999, over 1 million people have died of a drug overdose in the US. However, little is known about the bereaved, meaning their family, friends, and acquaintances, and their views on the importance of addiction as a policy priority., Objectives: To quantify the scope of the drug overdose crisis in terms of personal overdose loss (ie, knowing someone who died of a drug overdose) and to assess the policy implications of this loss., Design, Setting, and Participants: This cross-sectional study used data from a nationally representative survey of US adults (age ≥18 years), the fourth wave of the COVID-19 and Life Stressors Impact on Mental Health and Well-Being (CLIMB) study, which was conducted from March to April 2023., Main Outcomes and Measures: Respondents reported whether they knew someone who died of a drug overdose and the nature of their relationship with the decedent(s). They also reported their political party affiliation and rated the importance of addiction as a policy issue. Logistic regression models estimated the associations between sociodemographic characteristics and political party affiliation and the probability of experiencing a personal overdose loss and between the experience of overdose loss and the perceived salience of addiction as a policy issue. Survey weights adjusted for sampling design and nonresponse., Results: Of the 7802 panelists invited to participate, 2479 completed the survey (31.8% response rate); 153 were excluded because they did not know whether they knew someone who died of a drug overdose, resulting in a final analytic sample of 2326 (51.4% female; mean [SD] age, 48.12 [0.48] years). Of these respondents, 32.0% (95% CI, 28.8%-34.3%) reported any personal overdose loss, translating to 82.7 million US adults. A total of 18.9% (95% CI, 17.1%-20.8%) of all respondents, translating to 48.9 million US adults, reported having a family member or close friend die of drug overdose. Personal overdose loss was more prevalent among groups with lower income (<$30 000: 39.9%; ≥$100 000: 26.0%). The experience of overdose loss did not differ across political party groups (Democrat: 29.0%; Republican: 33.0%; independent or none: 34.2%). Experiencing overdose loss was associated with a greater odds of viewing addiction as an extremely or very important policy issue (adjusted odds ratio, 1.37; 95% CI, 1.09-1.72) after adjustment for sociodemographic and geographic characteristics and political party affiliation., Conclusions and Relevance: This cross-sectional study found that 32% of US adults reported knowing someone who died of a drug overdose and that personal overdose loss was associated with greater odds of endorsing addiction as an important policy issue. The findings suggest that mobilization of this group may be an avenue to facilitate greater policy change.

Importance: Given the high number of opioid overdose deaths in the US and the complex epidemiology of opioid use disorder (OUD), systems models can serve as a tool to identify opportunities for public health interventions., Objective: To estimate the projected 3-year association between public health interventions and opioid overdose-related outcomes among persons with OUD., Design, Setting, and Participants: This decision analytical model used a simulation model of the estimated US population aged 12 years and older with OUD that was developed and analyzed between January 2019 and December 2023. The model was parameterized and calibrated using 2019 to 2020 data and used to estimate the relative change in outcomes associated with simulated public health interventions implemented between 2021 and 2023., Main Outcomes and Measures: Projected OUD and medications for OUD (MOUD) prevalence in 2023 and number of nonfatal and fatal opioid-involved overdoses among persons with OUD between 2021 and 2023., Results: In a baseline scenario assuming parameters calibrated using 2019 to 2020 data remained constant, the model projected more than 16 million persons with OUD not receiving MOUD treatment and nearly 1.7 million persons receiving MOUD treatment in 2023. Additionally, the model projected over 5 million nonfatal and over 145 000 fatal opioid-involved overdoses among persons with OUD between 2021 and 2023. When simulating combinations of interventions that involved reducing overdose rates by 50%, the model projected decreases of up to 35.2% in nonfatal and 36.6% in fatal opioid-involved overdoses among persons with OUD. Interventions specific to persons with OUD not currently receiving MOUD treatment demonstrated the greatest reduction in numbers of nonfatal and fatal overdoses. Combinations of interventions that increased MOUD initiation and decreased OUD recurrence were projected to reduce OUD prevalence by up to 23.4%, increase MOUD prevalence by up to 137.1%, and reduce nonfatal and fatal opioid-involved overdoses among persons with OUD by 6.7% and 3.5%, respectively., Conclusions and Relevance: In this decision analytical model study of persons with OUD, findings suggested that expansion of evidence-based interventions that directly reduce the risk of overdose fatality among persons with OUD, such as through harm reduction efforts, could engender the highest reductions in fatal overdoses in the short-term. Interventions aimed at increasing MOUD initiation and retention of persons in treatment projected considerable improvement in MOUD and OUD prevalence but could require a longer time horizon for substantial reductions in opioid-involved overdoses.

Importance: Patients treated in emergency departments (EDs) for opioid overdose often need drug treatment yet are rarely linked to services after discharge. Emergency department-based peer support is a promising approach for promoting treatment linkage, but evidence of its effectiveness is lacking., Objective: To examine the association of the Opioid Overdose Recovery Program (OORP), an ED peer recovery support service, with postdischarge addiction treatment initiation, repeat overdose, and acute care utilization., Design, Setting, and Participants: This intention-to-treat retrospective cohort study used 2014 to 2020 New Jersey Medicaid data for Medicaid enrollees aged 18 to 64 years who were treated for nonfatal opioid overdose from January 2015 to June 2020 at 70 New Jersey acute care hospitals. Data were analyzed from August 2022 to November 2023., Exposure: Hospital OORP implementation., Main Outcomes and Measures: The primary outcome was medication for opioid use disorder (MOUD) initiation within 60 days of discharge. Secondary outcomes included psychosocial treatment initiation, medically treated drug overdoses, and all-cause acute care visits after discharge. An event study design was used to compare 180-day outcomes between patients treated in OORP hospitals and those treated in non-OORP hospitals. Analyses adjusted for patient demographics, comorbidities, and prior service use and for community-level sociodemographics and drug treatment access., Results: A total of 12 046 individuals were included in the study (62.0% male). Preimplementation outcome trends were similar for patients treated in OORP and non-OORP hospitals. Implementation of the OORP was associated with an increase of 0.034 (95% CI, 0.004-0.064) in the probability of 60-day MOUD initiation in the half-year after implementation, representing a 45% increase above the preimplementation mean probability of 0.075 (95% CI, 0.066-0.084). Program implementation was associated with fewer repeat medically treated overdoses 4 half-years (-0.086; 95% CI, -0.154 to -0.018) and 5 half-years (-0.106; 95% CI, -0.184 to -0.028) after implementation. Results differed slightly depending on the reference period used, and hospital-specific models showed substantial heterogeneity in program outcomes across facilities., Conclusions and Relevance: In this cohort study of patients treated for opioid overdose, OORP implementation was associated with an increase in MOUD initiation and a decrease in repeat medically treated overdoses. The large variation in outcomes across hospitals suggests that treatment effects were heterogeneous and may depend on factors such as implementation success, program embeddedness, and availability of other hospital- and community-based OUD services.

Importance: In March 2020, British Columbia, Canada, became the first jurisdiction globally to launch a large-scale provincewide safer supply policy. The policy allowed individuals with opioid use disorder at high risk of overdose or poisoning to receive pharmaceutical-grade opioids prescribed by a physician or nurse practitioner, but to date, opioid-related outcomes after policy implementation have not been explored., Objective: To investigate the association of British Columbia's Safer Opioid Supply policy with opioid prescribing and opioid-related health outcomes., Design, Setting, and Participants: This cohort study used quarterly province-level data from quarter 1 of 2016 (January 1, 2016) to quarter 1 of 2022 (March 31, 2022), from British Columbia, where the Safer Opioid Supply policy was implemented, and Manitoba and Saskatchewan, where the policy was not implemented (comparison provinces)., Exposure: Safer Opioid Supply policy implemented in British Columbia in March 2020., Main Outcomes and Measures: The main outcomes were rates of prescriptions, claimants, and prescribers of opioids targeted by the Safer Opioid Supply policy (hydromorphone, morphine, oxycodone, and fentanyl); opioid-related poisoning hospitalizations; and deaths from apparent opioid toxicity. Difference-in-differences analysis was used to compare changes in outcomes before and after policy implementation in British Columbia with those in the comparison provinces., Results: The Safer Opioid Supply policy was associated with statistically significant increases in rates of opioid prescriptions (2619.6 per 100 000 population; 95% CI, 1322.1-3917.0 per 100 000 population; P < .001) and claimants (176.4 per 100 000 population; 95% CI, 33.5-319.4 per 100 000 population; P = .02). There was no significant change in prescribers (15.7 per 100 000 population; 95% CI, -0.2 to 31.6 per 100 000 population; P = .053). However, the opioid-related poisoning hospitalization rate increased by 3.2 per 100 000 population (95% CI, 0.9-5.6 per 100 000 population; P = .01) after policy implementation. There were no statistically significant changes in deaths from apparent opioid toxicity (1.6 per 100 000 population; 95% CI, -1.3 to 4.5 per 100 000 population; P = .26)., Conclusions and Relevance: Two years after its launch, the Safer Opioid Supply policy in British Columbia was associated with higher rates of safer supply opioid prescribing but also with a significant increase in opioid-related poisoning hospitalizations. These findings will help inform ongoing debates about this policy not only in British Columbia but also in other jurisdictions that are contemplating it.

Importance: Two states modified laws to remove or substantially reduce criminal penalties for any drug possession. The hypothesis was that removing criminal penalties for drug possession may reduce fatal drug overdoses due to reduced incarceration and increased calls for help at the scene of an overdose., Objective: To evaluate whether decriminalization of drug possession in Oregon and Washington was associated with changes in either direction in fatal drug overdose rates., Design, Setting, and Participants: This cohort study used a synthetic control method approach to examine whether there were changes in drug possession laws and fatal drug overdose rates in Oregon and Washington in the postpolicy period (February 1, 2021, to March 31, 2022, in Oregon and March 1, 2021, to March 31, 2022, in Washington). A counterfactual comparison group (synthetic controls) was created for Oregon and Washington, using 48 states and the District of Columbia, that did not implement similar policies during the study period (January 1, 2018, to March 31, 2022). For 2018-2021, final multiple cause-of-death data from the National Vital Statistics System (NVSS) were used. For 2022, provisional NVSS data were used. Drug overdose deaths were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision underlying cause-of-death codes X40-X44, X60-X64, X85, and Y10-Y14., Exposures: In Oregon, Measure 110 went into effect on February 1, 2021. In Washington, the Washington Supreme Court decision in State v Blake occurred on February 25, 2021., Main Outcome: Monthly fatal drug overdose rates., Results: Following the implementation of Measure 110, absolute monthly rate differences between Oregon and its synthetic control were not statistically significant (probability = 0.26). The average rate difference post Measure 110 was 0.268 fatal drug overdoses per 100 000 state population. Following the implementation of the policy change in Washington, the absolute monthly rate differences between Washington and synthetic Washington were not statistically significant (probability = 0.06). The average rate difference post Blake was 0.112 fatal drug overdoses per 100 000 state population., Conclusions and Relevance: This study found no evidence of an association between legal changes that removed or substantially reduced criminal penalties for drug possession in Oregon and Washington and fatal drug overdose rates. Additional research could examine potential other outcomes as well as longer-term associations with fatal drug overdose overall and across racial and ethnic groups.

Importance: The first government-sanctioned overdose prevention centers (OPCs) in the US opened in New York City (NYC) in November 2021 amid concerns that they may increase crime and disorder, representing a significant political challenge to OPCs., Objective: To identify whether opening the first 2 government-sanctioned OPCs in the US was associated with changes in crime and disorder., Design, Setting, and Participants: In this cohort study, difference-in-differences Poisson regression models were used to compare crime, residents' requests for assistance for emergencies and nuisance complaints, and police enforcement in the vicinity of NYC's 2 OPCs with those around 17 other syringe service programs that did not offer overdose prevention services from January 1, 2019, through December 31, 2022., Main Outcomes and Measures: Changes in the volume of crimes reported by the public or observed by police; arrests for drug possession and weapons; 911 calls and 311 calls regarding crime, public nuisances, and medical events; and summonses issued by police for criminal infractions in both the immediate vicinity of the sites (ie, a hexagonal area spanning about 6 city blocks) and their wider neighborhoods (ie, a tesselated 3-hexagon array spanning about 18 city blocks)., Results: No significant changes were detected in violent crimes or property crimes recorded by police, 911 calls for crime or medical incidents, or 311 calls regarding drug use or unsanitary conditions observed in the vicinity of the OPCs. There was a significant decline in low-level drug enforcement, as reflected by a reduction in arrests for drug possession near the OPCs of 82.7% (95% CI, -89.9% to -70.4%) and a reduction in their broader neighborhoods of 74.5% (95% CI, -87.0% to -50.0%). Significant declines in criminal court summonses issued in the immediate vicinity by 87.9% (95% CI, -91.9% to -81.9%) and in the neighborhoods around the OPCs by 59.7% (95% CI, -73.8% to -38.0%) were observed. Reductions in enforcement were consistent with the city government's support for the 2 OPCs, which may have resulted in a desire not to deter clients from using the sites by fear of arrest for drug possession., Conclusions and Relevance: In this difference-in-differences cohort study, the first 2 government-sanctioned OPCs in the US were not associated with significant changes in measures of crime or disorder. These observations suggest the expansion of OPCs can be managed without negative crime or disorder outcomes.

Importance: Determining the association between drug use and suicide is complicated but can help to inform targeted suicide prevention strategies., Objective: To examine the substances prevalent in poisoning- and nonpoisoning-related suicides in Australia., Design, Setting, and Participants: This was a multiple-year, cross-sectional study of suicides from July 2013 to October 2019 in Australia with toxicology data available in a national coronial database. The cause of death was classified as poisoning related if any type of poisoning was determined by the coroner to contribute to the cause of death. Prevalence ratios (PRs) were calculated to compare substance detection in poisoning- vs nonpoisoning-related suicides. Data were analyzed from October 2021 to April 2023., Exposures: All substances detected in decedents at the time of death according to toxicology reports were recorded., Main Outcome(s) and Measure(s): The most common individual substances and substance classes were identified. From these, blood concentrations of substances of interest were analyzed, and the most commonly occurring combinations of substance classes were listed., Results: Toxicology was performed on 13 664 suicide decedents (median [IQR] age, 44 [31-57] years; 10 350 male [76%]). From these, 3397 (25%) were poisoning-related suicides (median [IQR] age, 50 [38-63] years; 2124 male [63%]). The remainder were classified as nonpoisoning-related suicides (median [IQR] age, 42 [29-55] years; 8226 male [80%]). PRs for common medicine classes being detected in poisoning-related suicides compared with nonpoisoning-related suicides were as follows: antidepressants (PR, 1.63; 95% CI, 1.54-1.73), benzodiazepines (PR, 2.01; 95% CI, 1.90-2.13), nonopioid analgesics/anti-inflammatory drugs (PR, 1.88; 95% CI, 1.78-2.00), and opioids (PR, 2.72; 95% CI, 2.58-2.87). Alcohol (as ethanol ≥0.03 g/100 mL) was almost equally prevalent in poisoning- and nonpoisoning-related deaths (PR, 1.07; 95% CI, 1.01-1.14), whereas amphetamines (PR, 0.68; 95% CI, 0.61-0.77) and cannabinoids (PR, 0.67; 95% CI, 0.60-0.74) were detected more often in nonpoisoning-related suicides. Combinations of multiple sedative agents in poisoning-related suicides were common., Conclusions and Relevance: Both poisoning- and nonpoisoning-related suicide deaths featured a high prevalence of psychotropic medicines or potential intoxication, which suggests the association of suicide with poor mental health and substance misuse. Findings suggest that substances with a high involvement in poisoning-related suicides should be prescribed cautiously, including antidepressants that are toxic in overdose, sedatives, opioids, and potentially lethal combinations.

Importance: Drug use and incarceration have a substantial impact on rural communities, but factors associated with the incarceration of rural people who use drugs (PWUD) have not been thoroughly investigated., Objective: To characterize associations between recent incarceration, overdose, and substance use disorder (SUD) treatment access among rural PWUD., Design, Setting, and Participants: For this cross-sectional study, the Rural Opioid Initiative research consortium conducted a survey in geographically diverse rural counties with high rates of overdose across 10 US states (Illinois, Wisconsin, North Carolina, Oregon, Kentucky, West Virginia, Ohio, Massachusetts, New Hampshire, and Vermont) between January 25, 2018, and March 17, 2020, asking PWUD about their substance use, substance use treatment, and interactions with the criminal legal system. Participants were recruited through respondent-driven sampling in 8 rural US regions. Respondents who were willing to recruit additional respondents from their personal networks were enrolled at syringe service programs, community support organizations, and through direct community outreach; these so-called seed respondents then recruited others. Of 3044 respondents, 2935 included participants who resided in rural communities and reported past-30-day injection of any drug or use of opioids nonmedically via any route. Data were analyzed from February 8, 2022, to September 15, 2023., Exposure: Recent incarceration was the exposure of interest, defined as a report of incarceration in jail or prison for at least 1 day in the past 6 months., Main Outcomes and Measures: The associations between PWUD who were recently incarcerated and main outcomes of treatment use and overdose were examined using logistic regression., Results: Of 2935 participants, 1662 (56.6%) were male, 2496 (85.0%) were White; the mean (SD) age was 36 (10) years; and in the past 30 days, 2507 (85.4%) reported opioid use and 1663 (56.7%) reported injecting drugs daily. A total of 1224 participants (41.7%) reported recent incarceration, with a median (IQR) incarceration of 15 (3-60) days in the past 6 months. Recent incarceration was associated with past-6-month overdose (adjusted odds ratio [AOR], 1.38; 95% CI, 1.12-1.70) and recent SUD treatment (AOR, 1.62; 95% CI, 1.36-1.93) but not recent medication for opioid use disorder (MOUD; AOR, 1.03; 95% CI, 0.82-1.28) or currently carrying naloxone (AOR, 1.02; 95% CI, 0.86-1.21)., Conclusions and Relevance: In this cross-sectional study of PWUD in rural areas, participants commonly experienced recent incarceration, which was not associated with MOUD, an effective and lifesaving treatment. The criminal legal system should implement effective SUD treatment in rural areas, including MOUD and provision of naloxone, to fully align with evidence-based SUD health care policies.

Importance: Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training implementation. However, there was limited good-quality evidence in a systematic review of the association between THN access and subsequent risk compensation behaviors., Objective: To assess whether THN training is associated with changes in overdose risk behaviors, indexed through injecting frequency, in a cohort of people who inject drugs., Design, Setting, and Participants: This cohort study used prospectively collected self-reported behavioral data before and after THN training of participants in The Melbourne Injecting Drug User Cohort Study (SuperMIX). Annual interviews were conducted in and around Melbourne, Victoria, Australia, from 2008 to 2021. SuperMIX participants were adults who regularly injected heroin or methamphetamine in the 6 months preceding their baseline interview. The current study included only people who inject drugs who reported THN training and had participated in at least 1 interview before THN training., Exposure: In 2017, the SuperMIX baseline or follow-up survey began asking participants if and when they had received THN training. The first THN training date that was recorded was included as the exposure variable. Subsequent participant interviews were excluded from analysis., Main Outcomes and Measures: Injecting frequency was the primary outcome and was used as an indicator of overdose risk. Secondary outcomes were opioid injecting frequency, benzodiazepine use frequency, and the proportion of the time drugs were used alone. Fixed-effects generalized linear (Poisson) multilevel modeling was used to estimate the association between THN training and the primary and secondary outcomes. Time-varying covariates included housing status, income, time in study, recent opioid overdose, recent drug treatment, and needle and syringe coverage. Findings were expressed as incidence rate ratios (IRRs) with 95% CIs., Results: There were 1328 participants (mean [SD] age, 32.4 [9.0] years; 893 men [67.2%]) who completed a baseline interview in the SuperMIX cohort, and 965 participants completed either a baseline or follow-up interview in or after 2017. Of these 965 participants, 390 (40.4%) reported THN training. A total of 189 people who inject drugs had pretraining participant interviews with data on injecting frequency and were included in the final analysis (mean [SD] number of interviews over the study period, 6.2 [2.2]). In fixed-effects regression analyses adjusted for covariates, there was no change in the frequency of injecting (IRR, 0.91; 95% CI, 0.69-1.20; P = .51), opioid injecting (IRR, 0.95; 95% CI, 0.74-1.23; P = .71), benzodiazepine use (IRR, 0.96; 95% CI, 0.69-1.33; P = .80), or the proportion of reported time of using drugs alone (IRR, 1.04; 95% CI, 0.86-1.26; P = .67) before and after THN training., Conclusions and Relevance: This cohort study of people who inject drugs found no evidence of an increase in injecting frequency, along with other markers of overdose risk, after THN training and supply. The findings suggest that THN training should not be withheld because of concerns about risk compensation and that advocacy for availability and uptake of THN is required to address unprecedented opioid-associated mortality.

Importance: Synthetic opioids, such as the fentanyl analogue and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency department (ED) with illicit opioid overdose (OD). However, clinical outcomes from OD of novel potent opioids (NPOs), specifically nitazenes, are unknown aside from small case series., Objective: To determine naloxone administration and clinical sequelae of patients who were in the ED with NPO overdose compared with fentanyl OD., Design, Setting, and Participants: This is a cohort study subgroup analysis of adults admitted to the ED and tested positive for NPOs among in the ongoing nationwide ToxIC Fentalog cohort study from 2020 to 2022. Patients who were in the ED with a presumed acute opioid OD and residual blood samples were included, and those testing positive for NPOs were analyzed. Patients were included in this analysis if their confirmatory testing was positive for an NPO analyte, such as brorphine, isotonitazene, metonitazene, and/or N-piperidinyl etonitazene. A comparison group included patients that were positive for fentanyl and devoid of any other analytes on toxicologic analysis., Exposures: Patients were exposed to NPOs, including brorphine, isotonitazene, metonitazene and/or N-piperidinyl etonitazene., Main Outcomes and Measures: The primary outcome was the total number of naloxone doses and total cumulative naloxone dose administered as part of routine clinical care following the OD. Naloxone requirements and clinical sequelae of NPO-positive patients were compared with those testing positive for fentanyl only., Results: During the study period, 2298 patients were screened, of whom 717 met inclusion criteria, 537 had complete laboratory testing data, with 11 (2.0%) positive for only fentanyl and 9 (1.7%) positive for NPOs (brorphine, isotonitazene, metonitazene, or N-piperidinyl etonitazene). The age range of patients was aged 20 to 57 years (4 males [44.4%] and 5 females [55.6%]). The NPO group received a statistically significantly higher mean (SD) number of naloxone boluses in-hospital (1.33 [1.50]) compared with the fentanyl group (0.36 [0.92]) (P = .02), which corresponded to a moderately large effect size (Cohen d = 0.78). Metonitazene overdose was associated with cardiac arrest and more naloxone doses overall. Metonitazene cases had a mean (SD) number of 3.0 (0) naloxone doses, and 2 of 2 patients (100%) with metonitazene overdoses were administered cardiopulmonary resuscitation., Conclusions and Relevance: In this cohort study of patients admitted to the ED with confirmed opioid overdose testing positive for NPOs, in-hospital naloxone dosing was high compared with patients who tested positive for fentanyl alone. Further study is warranted to confirm these preliminary associations.

Importance: The opioid crisis disproportionately affects Medicaid enrollees, yet little systematic evidence exists regarding how prevalence of and health care utilization for opioid use disorder (OUD) vary across geographical areas., Objectives: To characterize state- and county-level variation in claims-based prevalence of OUD and rates of medication treatment for OUD and OUD-related nonfatal overdose among Medicaid enrollees., Design, Setting, and Participants: This cross-sectional study used data from the Transformed Medicaid Statistical Information System Analytic Files from January 1, 2016, to December 31, 2018. Participants were Medicaid enrollees with or without OUD in 46 states; Washington, DC; and Puerto Rico who were aged 18 to 64 years and not dually enrolled in Medicare. The analysis was conducted between September 2022 and April 2023., Exposure: Calendar-year OUD prevalence., Main Outcomes and Measures: The main outcomes were claims-based measures of OUD prevalence and rates of medication treatment for OUD and opioid-related nonfatal overdose. Individual records were aggregated at the state and county level, and variation was assessed within and across states., Results: Of the 76 390 817 Medicaid enrollee-year observations included in our study (mean [SD] enrollee age, 36.5 [1.6] years; 59.0% female), 2 280 272 (3.0%) had a claims-based OUD (mean [SD] age, 38.9 [3.6] years; 51.4% female). Of enrollees with OUD, 41.2% were eligible due to Medicaid expansion, 46.4% had other substance use disorders, 55.8% had mental health conditions, 55.2% had claims indicating some form of OUD medication, and 5.8% had claims indicating an overdose during a calendar year. Claims-based outcomes exhibited substantial variation across states: OUD prevalence ranged from 0.6% in Arkansas and Puerto Rico to 9.7% in Maryland, rates of OUD medication treatment ranged from 17.7% in Kansas to 82.8% in Maine, and rates of overdose ranged from 0.3% in Mississippi to 10.5% in Illinois. Pronounced variation was also found within states (eg, OUD prevalence in Maryland ranged from 2.2% in Prince George's County to 21.6% in Cecil County)., Conclusions and Relevance: In this cross-sectional study of Medicaid enrollees from 2016 to 2018, claims-based prevalence of OUD and rates of OUD medication treatment and opioid-related overdose varied substantially across and within states. Further research appears to be needed to identify important factors influencing this variation.

Importance: Health departments have used a variety of methods for overdose surveillance, and the Centers for Disease Control and Prevention (CDC) is implementing a standardized case definition to improve overdose surveillance nationally. The comparative accuracy of the CDC opioid overdose case definition vs existing state opioid overdose surveillance systems is unknown., Objective: To evaluate the accuracy of the CDC opioid overdose case definition and existing Rhode Island Department of Health (RIDOH) state opioid overdose surveillance system., Design, Setting, and Participants: This cross-sectional study of ED opioid overdose visits was conducted at 2 EDs in Providence, Rhode Island, at the state's largest health system from January to May 2021. Electronic health records (EHRs) were reviewed for opioid overdoses identified by the CDC case definition and opioid overdoses reported to the RIDOH state surveillance system. Included patients were those at study EDs whose visit met the CDC case definition, was reported to the state surveillance system, or both. True overdose cases were confirmed by EHR review using a standard case definition; 61 of 460 EHRs (13.3%) were double reviewed to estimate classification accuracy. Data were analyzed from January through May 2021., Main Outcome and Measure: Accurate identification of an opioid overdose was assessed by estimating the positive predictive value of the CDC case definition and state surveillance system using results from the EHR review., Results: Among 460 ED visits that met the CDC opioid overdose case definition, were reported to the RIDOH opioid overdose surveillance system, or both (mean [SD] age, 39.7 [13.5] years; 313 males [68.0%]; 61 Black [13.3%], 308 White [67.0%], and 91 other race [19.8%]; and 97 Hispanic or Latinx [21.1%] among each patient visit), 359 visits (78.0%) were true opioid overdoses. For these visits, the CDC case definition and RIDOH surveillance system agreed that 169 visits (36.7%) were opioid overdoses. Of 318 visits meeting the CDC opioid overdose case definition, 289 visits (90.8%; 95% CI, 87.2%-93.8%) were true opioid overdoses. Of 311 visits reported to the RIDOH surveillance system, 235 visits (75.6%; 95% CI, 70.4%-80.2%) were true opioid overdoses., Conclusions and Relevance: This cross-sectional study found that the CDC opioid overdose case definition more often identified true opioid overdoses compared with the Rhode Island overdose surveillance system. This finding suggests that using the CDC case definition for opioid overdose surveillance may be associated with improved data efficiency and uniformity.

Importance: In 2021, more than 80 000 US residents died from an opioid overdose. Public health intervention initiatives, such as the Helping to End Addiction Long-term (HEALing) Communities Study (HCS), are being launched with the goal of reducing opioid-related overdose deaths (OODs)., Objective: To estimate the change in the projected number of OODs under different scenarios of the duration of sustainment of interventions, compared with the status quo., Design, Setting, and Participants: This decision analytical model simulated the opioid epidemic in the 4 states participating in the HCS (ie, Kentucky, Massachusetts, New York, and Ohio) from 2020 to 2026. Participants were a simulated population transitioning from opioid misuse to opioid use disorder (OUD), overdose, treatment, and relapse. The model was calibrated using 2015 to 2020 data from the National Survey on Drug Use and Health, the US Centers for Disease Control and Prevention, and other sources for each state. The model accounts for reduced initiation of medications for OUD (MOUDs) and increased OODs during the COVID-19 pandemic., Exposure: Increasing MOUD initiation by 2- or 5-fold, improving MOUD retention to the rates achieved in clinical trial settings, increasing naloxone distribution efforts, and furthering safe opioid prescribing. An initial 2-year duration of interventions was simulated, with potential sustainment for up to 3 additional years., Main Outcomes and Measures: Projected reduction in number of OODs under different combinations and durations of sustainment of interventions., Results: Compared with the status quo, the estimated annual reduction in OODs at the end of the second year of interventions was 13% to 17% in Kentucky, 17% to 27% in Massachusetts, 15% to 22% in New York, and 15% to 22% in Ohio. Sustaining all interventions for an additional 3 years was estimated to reduce the annual number of OODs at the end of the fifth year by 18% to 27% in Kentucky, 28% to 46% in Massachusetts, 22% to 34% in New York, and 25% to 41% in Ohio. The longer the interventions were sustained, the better the outcomes; however, these positive gains would be washed out if interventions were not sustained., Conclusions and Relevance: In this decision analytical model study of the opioid epidemic in 4 US states, sustained implementation of interventions, including increased delivery of MOUDs and naloxone supply, was found to be needed to reduce OODs and prevent deaths from increasing again.

Importance: At least 500 000 people in the US experience homelessness nightly. More than 30% of people experiencing homelessness also have a substance use disorder. Involuntary displacement is a common practice in responding to unsheltered people experiencing homelessness. Understanding the health implications of displacement (eg, "sweeps," "clearings," "cleanups") is important, especially as they relate to key substance use disorder outcomes., Objective: To estimate the long-term health effects of involuntary displacement of people experiencing homelessness who inject drugs in 23 US cities., Design, Setting, and Participants: A closed cohort microsimulation model that simulates the natural history of injection drug use and health outcomes among people experiencing homelessness who inject drugs in 23 US cities. The model was populated with city-level data from the Centers for Disease Control and Prevention's National HIV Behavioral Surveillance system and published data to make representative cohorts of people experiencing homelessness who inject drugs in those cities., Main Outcomes and Measures: Projected outcomes included overdose mortality, serious injection-related infections and mortality related to serious injection-related infections, hospitalizations, initiations of medications for opioid use disorder, and life-years lived over a 10-year period for 2 scenarios: "no displacement" and "continual involuntary displacement." The population-attributable fraction of continual displacement to mortality was estimated among this population., Results: Models estimated between 974 and 2175 additional overdose deaths per 10 000 people experiencing homelessness at 10 years in scenarios in which people experiencing homelessness who inject drugs were continually involuntarily displaced compared with no displacement. Between 611 and 1360 additional people experiencing homelessness who inject drugs per 10 000 people were estimated to be hospitalized with continual involuntary displacement, and there will be an estimated 3140 to 8812 fewer initiations of medications for opioid use disorder per 10 000 people. Continual involuntary displacement may contribute to between 15.6% and 24.4% of additional deaths among unsheltered people experiencing homelessness who inject drugs over a 10-year period., Conclusion and Relevance: Involuntary displacement of people experiencing homelessness may substantially increase drug-related morbidity and mortality. These findings have implications for the practice of involuntary displacement, as well as policies such as access to housing and supportive services, that could mitigate these harms.

Importance: Federal emergency authorities were invoked during the COVID-19 pandemic to expand clinical telehealth for opioid use disorder (OUD)., Objective: To examine the association of the receipt of telehealth services and medications for OUD (MOUD) with fatal drug overdoses before and during the pandemic., Design, Setting, and Participants: This cohort study used exploratory longitudinal data from 2 cohorts (prepandemic cohort: September 1, 2018, to February 29, 2020; pandemic cohort: September 1, 2019, to February 28, 2021) of Medicare Fee-for-Service beneficiaries aged 18 years or older initiating an episode of OUD-related care using Medicare Fee-for-Service data from the Centers for Medicare & Medicaid Services and National Death Index data from the Centers for Disease Control and Prevention. Data analysis was performed from September 19 to October 17, 2022., Exposures: Prepandemic vs pandemic cohort demographic, medical, substance use, and psychiatric characteristics., Main Outcomes and Measures: Receipt of OUD-related telehealth services, receipt of MOUD, and fatal drug overdose., Results: The prepandemic cohort comprised 105 162 beneficiaries (58.1% female; 67.6% aged 45-74 years). The pandemic cohort comprised 70 479 beneficiaries (57.1% female; 66.3% aged 45-74 years). The rate of all-cause mortality was higher in the pandemic cohort (99.9 per 1000 beneficiaries; 7041 deaths) than in the prepandemic cohort (76.8 per 1000; 8076 deaths) (P < .001). The rate of fatal drug overdoses was higher in the pandemic cohort (5.1 per 1000 beneficiaries; n = 358) than in the prepandemic cohort (3.7 per 1000; n = 391) (P < .001). The percentage of deaths due to a fatal drug overdose was similar in the prepandemic (4.8%) and pandemic (5.1%) cohorts (P = .49). In multivariable analysis of the pandemic cohort, receipt of OUD-related telehealth was associated with a significantly lower adjusted odds ratio (aOR) for fatal drug overdose (aOR, 0.67; 95% CI, 0.48-0.92) as was receipt of MOUD from opioid treatment programs (aOR, 0.41; 95% CI, 0.25-0.68) and receipt of buprenorphine in office-based settings (aOR, 0.62; 95% CI, 0.43-0.91) compared with those not receiving MOUD; receipt of extended-release naltrexone in office-based settings was not associated with lower odds for fatal drug overdose (aOR, 1.16; 95% CI, 0.41-3.26)., Conclusions and Relevance: This cohort study found that, among Medicare beneficiaries initiating OUD-related care during the COVID-19 pandemic, receipt of OUD-related telehealth services was associated with reduced risk for fatal drug overdose, as was receipt of MOUD from opioid treatment programs and receipt of buprenorphine in office-based settings. Strategies to expand provision of MOUD, increase retention in care, and address co-occurring physical and behavioral health conditions are needed.

Importance: Most prisons and jails in the US discontinue medications for opioid use disorder (MOUD) upon incarceration and do not initiate MOUD prior to release., Objective: To model the association of MOUD access during incarceration and at release with population-level overdose mortality and OUD-related treatment costs in Massachusetts., Design, Setting, and Participants: This economic evaluation used simulation modeling and cost-effectiveness with costs and quality-adjusted life-years (QALYs) discounted at 3% to compare MOUD treatment strategies in a corrections cohort and an open cohort representing individuals with OUD in Massachusetts. Data were analyzed between July 1, 2021, and September 30, 2022., Exposures: Three strategies were compared: (1) no MOUD provided during incarceration or at release, (2) extended-release (XR) naltrexone offered only at release from incarceration, and (3) all 3 MOUDs (naltrexone, buprenorphine, and methadone) offered at intake., Main Outcomes and Measures: Treatment starts and retention, fatal overdoses, life-years and QALYs, costs, and incremental cost-effectiveness ratios (ICERs)., Results: Among 30 000 simulated incarcerated individuals with OUD, offering no MOUD was associated with 40 927 (95% uncertainty interval [UI], 39 001-42 082) MOUD treatment starts over a 5-year period and 1259 (95% UI, 1130-1323) overdose deaths after 5 years. Over 5 years, offering XR-naltrexone at release led to 10 466 (95% UI, 8515-12 201) additional treatment starts, 40 (95% UI, 16-50) fewer overdose deaths, and 0.08 (95% UI, 0.05-0.11) QALYs gained per person, at an incremental cost of $2723 (95% UI, $141-$5244) per person. In comparison, offering all 3 MOUDs at intake led to 11 923 (95% UI, 10 861-12 911) additional treatment starts, compared with offering no MOUD, 83 (95% UI, 72-91) fewer overdose deaths, and 0.12 (95% UI, 0.10-0.17) QALYs per person gained, at an incremental cost of $852 (95% UI, $14-$1703) per person. Thus, XR-naltrexone only was a dominated strategy (both less effective and more costly) and the ICER of all 3 MOUDs compared with no MOUD was $7252 (95% UI, $140-$10 018) per QALY. Among everyone with OUD in Massachusetts, XR-naltrexone only averted 95 overdose deaths over 5 years (95% UI, 85-169)-a 0.9% decrease in state-level overdose mortality-while the all-MOUD strategy averted 192 overdose deaths (95% UI, 156-200)-a 1.8% decrease., Conclusions and Relevance: The findings of this simulation-modeling economic study suggest that offering any MOUD to incarcerated individuals with OUD would prevent overdose deaths and that offering all 3 MOUDs would prevent more deaths and save money compared with an XR-naltrexone-only strategy.

Importance: Previous studies that examined the role of household opioid prescriptions in opioid overdose risk were limited to commercial claims, did not include fatal overdoses, and had limited inclusion of household prescription characteristics. Broader research is needed to expand understanding of the risk of overdose., Objective: To assess the role of household opioid availability and other household prescription factors associated with individuals' odds of fatal or nonfatal opioid overdose., Design, Setting, and Participants: A retrospective cohort study assessing patient outcomes from January 1, 2015, through December 31, 2018, was conducted on adults in the Oregon Comprehensive Opioid Risk Registry database in households of at least 2 members. Data analysis was performed between October 16, 2020, and January 26, 2023., Exposures: Household opioid prescription availability and household prescription characteristics., Main Outcomes and Measures: Opioid overdoses were captured from insurance claims, death records, and hospital discharge data. Household opioid prescription availability and prescription characteristics for individuals and households were modeled as 6-month cumulative time-dependent measures, updated monthly. To assess the association between household prescription availability, household prescription characteristics, and overdose, multilevel logistic regression models were developed, adjusting for demographic, clinical, household, and prescription characteristics., Results: The sample included 1 691 856 individuals in 1 187 140 households, of which most were women (53.2%), White race (70.7%), living in metropolitan areas (75.8%), and having commercial insurance (51.8%), no Elixhauser comorbidities (69.5%), and no opioid prescription fills in the study period (57.0%). A total of 28 747 opioid overdose events were observed during the study period (0.0526 per 100 person-months). Relative to individuals without personal or household opioid fills, the odds of opioid-related overdose increased by 60% when another household member had an opioid fill in the past 6 months (adjusted odds ratio [aOR], 1.60; 95% CI, 1.54-1.66) and were highest when both the individual and another household member had opioid fills in the preceding 6 months (aOR, 6.25; 95% CI, 6.09-6.40)., Conclusions and Relevance: In this cohort study of adult Oregon residents in households of at least 2 members, the findings suggest that household prescription availability is associated with increased odds of opioid overdose for others in the household, even if they do not have their own opioid prescription. These findings underscore the importance of educating patients about proper opioid disposal and the risks of household opioids.

Importance: Buprenorphine remains underused in treating opioid use disorder, despite its effectiveness. During the onset of the COVID-19 pandemic, the US government implemented prescribing flexibilities to support continued access., Objective: To determine whether buprenorphine-involved overdose deaths changed after implementing these policy changes and highlight characteristics and circumstances of these deaths., Design, Setting, and Participants: This cross-sectional study used data from the State Unintentional Drug Overdose Reporting System (SUDORS) to assess overdose deaths in 46 states and the District of Columbia occurring July 2019 to June 2021. Data were analyzed from March 7, 2022, to June 30, 2022., Main Outcomes and Measures: Buprenorphine-involved and other opioid-involved overdose deaths were examined. Monthly opioid-involved overdose deaths and the percentage involving buprenorphine were computed to assess trends. Proportions and exact 95% CIs of drug coinvolvement, demographics, and circumstances were calculated by group., Results: During July 2019 to June 2021, 32 jurisdictions reported 89 111 total overdose deaths and 74 474 opioid-involved overdose deaths, including 1955 buprenorphine-involved overdose deaths, accounting for 2.2% of all drug overdose deaths and 2.6% of opioid-involved overdose deaths. Median (IQR) age was similar for buprenorphine-involved overdose deaths (41 [34-55] years) and other opioid-involved overdose deaths (40 [31-52] years). A higher proportion of buprenorphine-involved overdose decedents, compared with other opioid-involved decedents, were female (36.1% [95% CI, 34.2%-38.2%] vs 29.1% [95% CI, 28.8%-29.4%]), non-Hispanic White (86.1% [95% CI, 84.6%-87.6%] vs 69.4% [95% CI, 69.1%-69.7%]), and residing in rural areas (20.8% [95% CI, 19.1%-22.5%] vs 11.4% [95% CI, 11.2%-11.7%]). Although monthly opioid-involved overdose deaths increased, the proportion involving buprenorphine fluctuated but did not increase during July 2019 to June 2021. Nearly all (92.7% [95% CI, 91.5%-93.7%]) buprenorphine-involved overdose deaths involved at least 1 other drug; higher proportions involved other prescription medications compared with other opioid-involved overdose deaths (eg, anticonvulsants: 18.6% [95% CI, 17.0%-20.3%] vs 5.4% [95% CI, 5.2%-5.5%]) and a lower proportion involved illicitly manufactured fentanyls (50.2% [95% CI, 48.1%-52.3%] vs 85.3% [95% CI, 85.1%-85.5%]). Buprenorphine decedents were more likely to be receiving mental health treatment than other opioid-involved overdose decedents (31.4% [95% CI, 29.3%-33.5%] vs 13.3% [95% CI, 13.1%-13.6%])., Conclusions and Relevance: The findings of this cross-sectional study suggest that actions to facilitate access to buprenorphine-based treatment for opioid use disorder during the COVID-19 pandemic were not associated with an increased proportion of overdose deaths involving buprenorphine. Efforts are needed to expand more equitable and culturally competent access to and provision of buprenorphine-based treatment.

Importance: Studies have suggested a rise in opioid- and stimulant-involved overdoses in recent years in North America. This risk may be acute for individuals who have had contact with the criminal justice system, who are particularly vulnerable to overdose risk., Objective: To examine the association of opioid and/or stimulant use disorder diagnoses with overdose (fatal and nonfatal) among people with histories of incarceration., Design, Setting, and Participants: In this cohort study, population-based health and corrections data were retrieved from the British Columbia Provincial Overdose Cohort, which contains a 20% random sample of residents of British Columbia. The analysis included all people in the 20% random sample who had a history of incarceration between January 1, 2010, and December 31, 2014. Outcomes were derived from 5-years of follow-up data (January 1, 2015, to December 31, 2019). Statistical analysis took place from January 2022 to June 2022., Exposures: Substance use disorder diagnosis type (ie, opioid use disorder, stimulant use disorder, both, or neither), sociodemographic, health, and incarceration characteristics., Main Outcomes and Measures: Hazard ratios (HRs) are reported from an Andersen-Gill model for recurrent nonfatal overdose events and from a Fine and Gray competing risk model for fatal overdose events., Results: The study identified 6816 people (5980 male [87.7%]; 2820 aged <30 years [41.4%]) with histories of incarceration. Of these, 293 (4.3%) had opioid use disorder only, 395 (6.8%) had stimulant use disorder only, and 281 (4.1%) had both diagnoses. During follow-up, 1655 people experienced 4026 overdoses including 3781 (93.9%) nonfatal overdoses, and 245 (6.1%) fatal overdoses. In adjusted analyses, the hazard of both fatal (HR, 2.39; 95% CI, 1.48-3.86) and nonfatal (HR, 2.45; 95% CI, 1.94-3.11) overdose was highest in the group with both opioid and stimulant use disorder diagnoses., Conclusions and Relevance: This cohort study of people with a history of incarceration found an elevated hazard of fatal and nonfatal overdose among people with both opioid and stimulant use disorder diagnoses. This study suggests an urgent need to address the service needs of individuals who have had contact with the criminal justice system and who co-use opioids and stimulants.

Importance: In 2021, the state of Rhode Island distributed 10 000 additional naloxone kits compared with the prior year through partnerships with community-based organizations., Objective: To compare various strategies to increase naloxone distribution through community-based programs in Rhode Island to identify one most effective and efficient strategy in preventing opioid overdose deaths (OODs)., Design, Setting, and Participants: In this decision analytical model study conducted from January 2016 to December 2022, a spatial microsimulation model with an integrated decision tree was developed and calibrated to compare the outcomes of alternative strategies for distributing 10 000 additional naloxone kits annually among all individuals at risk for opioid overdose in Rhode Island., Interventions: Distribution of 10 000 additional naloxone kits annually, focusing on people who inject drugs, people who use illicit opioids and stimulants, individuals at various levels of risk for opioid overdose, or people who misuse prescription opioids vs no additional kits (status quo). Two expanded distribution implementation approaches were considered: one consistent with the current spatial distribution patterns for each distribution program type (supply-based approach) and one consistent with the current spatial distribution of individuals in each of the risk groups, assuming that programs could direct the additional kits to new geographic areas if required (demand-based approach)., Main Outcomes and Measures: Witnessed OODs, cost per OOD averted (efficiency), geospatial health inequality measured by the Theil index, and between-group variance for OOD rates., Results: A total of 63 131 simulated individuals were estimated to be at risk for opioid overdose in Rhode Island based on current population data. With the supply-based approach, prioritizing additional naloxone kits to people who use illicit drugs averted more witnessed OODs by an estimated mean of 18.9% (95% simulation interval [SI], 13.1%-30.7%) annually. Expanded naloxone distribution using the demand-based approach and focusing on people who inject drugs had the best outcomes across all scenarios, averting an estimated mean of 25.3% (95% SI, 13.1%-37.6%) of witnessed OODs annually, at the lowest mean incremental cost of $27 312 per OOD averted. Other strategies were associated with fewer OODs averted at higher costs but showed similar patterns of improved outcomes and lower unit costs if kits could be reallocated to areas with greater need. The demand-based approach reduced geospatial inequality in OOD rates in all scenarios compared with the supply-based approach and status quo., Conclusions and Relevance: In this decision analytical model study, variations in the effectiveness, efficiency, and health inequality of the different naloxone distribution expansion strategies and approaches were identified. Future efforts should be prioritized for people at highest risk for overdose (those who inject drugs or use illicit drugs) and redirected toward areas with the greatest need. These findings may inform future naloxone distribution priority settings.

Importance: Federal emergency authorities were invoked during the COVID-19 pandemic to expand use of telehealth for new and continued care, including provision of medications for opioid use disorder (MOUD)., Objective: To examine receipt of telehealth services, MOUD (methadone, buprenorphine, and extended-release [ER] naltrexone) receipt and retention, and medically treated overdose before and during the COVID-19 pandemic., Design, Setting, and Participants: This exploratory longitudinal cohort study used data from the US Centers for Medicare & Medicaid Services from September 2018 to February 2021. Two cohorts (before COVID-19 pandemic from September 2018 to February 2020 and during COVID-19 pandemic from September 2019 to February 2021) of Medicare fee-for-service beneficiaries 18 years and older with an International Statistical Classification of Diseases, Tenth Revision, Clinical Modification OUD diagnosis., Exposures: Pre-COVID-19 pandemic vs COVID-19 pandemic cohort demographic characteristics, medical and substance use, and psychiatric comorbidities., Main Outcomes and Measures: Receipt and retention of MOUD, receipt of OUD and behavioral health-related telehealth services, and experiencing medically treated overdose., Results: The pre-COVID-19 pandemic cohort comprised 105 240 beneficiaries; of these, 61 152 (58.1%) were female, 71 152 (67.6%) were aged 45 to 74 years, and 82 822 (79.5%) non-Hispanic White. The COVID-19 pandemic cohort comprised 70 538 beneficiaries; of these, 40 257 (57.1%) were female, 46 793 (66.3%) were aged 45 to 74 years, and 55 510 (79.7%) were non-Hispanic White. During the study period, a larger percentage of beneficiaries in the pandemic cohort compared with the prepandemic cohort received OUD-related telehealth services (13 829 [19.6%] vs 593 [0.6%]; P &lt; .001), behavioral health-related telehealth services (28 902 [41.0%] vs 1967 [1.9%]; P &lt; .001), and MOUD (8854 [12.6%] vs 11 360 [10.8%]; P &lt; .001). The percentage experiencing a medically treated overdose during the study period was similar (18.5% [19 491 of 105 240] in the prepandemic cohort vs 18.4% [13 004 of 70 538] in the pandemic cohort; P = .65). Receipt of OUD-related telehealth services in the pandemic cohort was associated with increased odds of MOUD retention (adjusted odds ratio [aOR], 1.27; 95% CI, 1.14-1.41) and lower odds of medically treated overdose (aOR, 0.67; 95% CI, 0.63-0.71). Among beneficiaries in the pandemic cohort, those receiving MOUD from opioid treatment programs only (aOR, 0.54; 95% CI, 0.47-0.63) and those receiving buprenorphine from pharmacies only (aOR, 0.91; 95% CI, 0.84-0.98) had lower odds of medically treated overdose compared with beneficiaries who did not receive MOUD., Conclusions and Relevance: Emergency authorities to expand use of telehealth and provide flexibilities for MOUD provision during the pandemic were used by Medicare beneficiaries initiating an episode of OUD-related care and were associated with improved retention in care and reduced odds of medically treated overdose. Strategies to expand provision of MOUD and increase retention in care are urgently needed.

Importance: Overdose is one of the leading causes of death in the US; however, surveillance data lag considerably from medical examiner determination of the death to reporting in national surveillance reports., Objective: To automate the classification of deaths related to substances in medical examiner data using natural language processing (NLP) and machine learning (ML)., Design, Setting, and Participants: Diagnostic study comparing different natural language processing and machine learning algorithms to identify substances related to overdose in 10 health jurisdictions in the US from January 1, 2020, to December 31, 2020. Unstructured text from 35 433 medical examiner and coroners' death records was examined., Exposures: Text from each case was manually classified to a substance that was related to the death. Three feature representation methods were used and compared: text frequency-inverse document frequency (TF-IDF), global vectors for word representations (GloVe), and concept unique identifier (CUI) embeddings. Several ML algorithms were trained and best models were selected based on F-scores. The best models were tested on a hold-out test set and results were reported with 95% CIs., Main Outcomes and Measures: Text data from death certificates were classified as any opioid, fentanyl, alcohol, cocaine, methamphetamine, heroin, prescription opioid, and an aggregate of other substances. Diagnostic metrics and 95% CIs were calculated for each combination of feature extraction method and machine learning classifier., Results: Of 35 433 death records analyzed (decedent median age, 58 years [IQR, 41-72 years]; 24 449 [69%] were male), the most common substances related to deaths included any opioid (5739 [16%]), fentanyl (4758 [13%]), alcohol (2866 [8%]), cocaine (2247 [6%]), methamphetamine (1876 [5%]), heroin (1613 [5%]), prescription opioids (1197 [3%]), and any benzodiazepine (1076 [3%]). The CUI embeddings had similar or better diagnostic metrics compared with word embeddings and TF-IDF for all substances except alcohol. ML classifiers had perfect or near perfect performance in classifying deaths related to any opioids, heroin, fentanyl, prescription opioids, methamphetamine, cocaine, and alcohol. Classification of benzodiazepines was suboptimal using all 3 feature extraction methods., Conclusions and Relevance: In this diagnostic study, NLP/ML algorithms demonstrated excellent diagnostic performance at classifying substances related to overdoses. These algorithms should be integrated into workflows to decrease the lag time in reporting overdose surveillance data.

Importance: Overdoses continue to increase in the US, but the contribution of methamphetamine use is understudied in rural communities., Objective: To estimate the prevalence of methamphetamine use and its correlates among people who use drugs (PWUD) in rural US communities and to determine whether methamphetamine use is associated with increased nonfatal overdoses., Design, Setting, and Participants: From January 2018 through March 2020, the National Rural Opioid Initiative conducted cross-sectional surveys of PWUD in rural communities in 10 states (Illinois, Kentucky, New Hampshire, Massachusetts, North Carolina, Ohio, Oregon, Vermont, West Virginia, and Wisconsin). Participants included rural PWUD who reported any past-30-day injection drug use or noninjection opioid use to get high. A modified chain-referral sampling strategy identified seeds who referred others using drugs. Data analysis was performed from May 2021 to January 2022., Exposures: Use of methamphetamine alone, opioids alone, or both., Main Outcomes and Measures: Unweighted and weighted prevalence of methamphetamine use, any past-180-day nonfatal overdose, and number of lifetime nonfatal overdoses., Results: Among the 3048 participants, 1737 (57%) were male, 2576 (85%) were White, and 225 (7.4%) were American Indian; the mean (SD) age was 36 (10) years. Most participants (1878 of 2970 participants with any opioid or methamphetamine use [63%]) reported co-use of methamphetamine and opioids, followed by opioids alone (702 participants [24%]), and methamphetamine alone (390 participants [13%]). The estimated unweighted prevalence of methamphetamine use was 80% (95% CI, 64%-90%), and the estimated weighted prevalence was 79% (95% CI, 57%-91%). Nonfatal overdose was greatest in people using both methamphetamine and opioids (395 of 2854 participants with nonmissing overdose data [22%]) vs opioids alone (99 participants [14%]) or methamphetamine alone (23 participants [6%]). Co-use of methamphetamine and opioids was associated with greater nonfatal overdose compared with opioid use alone (adjusted odds ratio, 1.45; 95% CI, 1.08-1.94; P = .01) and methamphetamine use alone (adjusted odds ratio, 3.26; 95% CI, 2.06-5.14; P < .001). Those with co-use had a mean (SD) of 2.4 (4.2) (median [IQR], 1 [0-3]) lifetime overdoses compared with 1.7 (3.5) (median [IQR], 0 [0-2]) among those using opioids alone (adjusted rate ratio, 1.20; 95% CI, 1.01-1.43; P = .04), and 1.1 (2.9) (median [IQR], 0 [0-1]) among those using methamphetamine alone (adjusted rate ratio, 1.81; 95% CI, 1.45-2.27; P < .001). Participants with co-use most often reported having tried and failed to access substance use treatment: 827 participants (44%) for both, 117 participants (30%) for methamphetamine alone, and 252 participants (36%) for opioids alone (χ22 = 33.8; P < .001). Only 66 participants (17%) using methamphetamine alone had naloxone., Conclusions and Relevance: These findings suggest that harm reduction and substance use disorder treatment interventions must address both methamphetamine and opioids to decrease overdose in rural communities.

Importance: Early identification of people who use opioids in pregnancy may improve health outcomes for pregnant people and infants. However, characterization of diverse circumstances surrounding type of opioid use and indications for opioid use are lacking., Objective: To develop clinically distinct groups of people who use opioids in pregnancy and to evaluate their association with drug overdose or death up to 1 year post partum., Design, Setting, and Participants: This is a population-based, repeated cross-sectional study conducted in Ontario, Canada, with participants who used opioids in pregnancy who had a live birth or stillbirth between January 1, 2014, and December 31, 2019, identified in health administrative databases. Data were analyzed from August 2020 to January 2021., Exposures: Prenatal opioid use., Main Outcomes and Measures: Latent class analysis (LCA), based on prenatal opioid use and 19 socioeconomic and medical characteristics, first identified clinically distinct groups of opioid users. Then, within the optimally derived LCA-derived group, adjusted relative risks (aRRs) were generated for the outcome of drug overdose or all-cause death within 1 year post partum, adjusting for birthing parent age and year of delivery., Results: The analysis included 31 241 people with prenatal opioid use (mean [SD] age, 30.0 [5.6] years; 86.1% [26 908 individuals] Canadian-born; 30.6% [9574 individuals] lived in low-income neighborhoods). LCA generated a 5-group model that optimally distinguished opioid users in pregnancy as follows: short-term analgesia with low comorbidity (group 1), analgesia in young people (group 2), medication for opioid use disorder or unregulated opioid use (group 3), pain management with comorbidity (group 4), and mixed opioid use plus high social and medical needs (group 5). The overall risk of postpartum drug overdose or death was 1.5%. Using the 5-group model, compared with people in group 1, the aRR of overdose or death was highest among those in group 5 (aRR, 14.0; 95% CI, 10.1-19.5), followed by group 3 (aRR, 4.6; 95% CI, 3.3-6.5), group 2 (aRR, 3.3; 95% CI, 2.2-4.7), and group 4 (aRR, 3.2; 95% CI, 2.3-4.4)., Conclusions and Relevance: In this cross-sectional study, distinct groups of people with opioid use in pregnancy were associated with increasing degrees of risk of postpartum drug overdose or death. Group characteristics can be used to identify people with high risk and inform harm reduction, home visiting programs, and other interventions.

Importance: A central tenet of harm reduction and prevention of opioid overdose deaths is the distribution and use of naloxone. Patient-centered methods that investigate naloxone acquisition and carrying can guide opioid overdose education and naloxone distribution efforts., Objective: To assess patients' self-reported naloxone acquisition and carrying after an emergency department (ED) encounter using automated text messaging., Design, Setting, and Participants: This cohort study investigated self-reported patient behaviors involving naloxone after ED discharge in a large, urban academic health system in Philadelphia, Pennsylvania. Adult patients who were prescribed or dispensed naloxone and who had a mobile phone number listed in the electronic health record provided informed consent after ED discharge, and data were collected prospectively using text messaging from October 10, 2020, to March 19, 2021. Patients who did not respond to the survey or who opted out were excluded., Exposure: Automated text message-based survey after ED discharge for patients who were prescribed or dispensed naloxone., Main Outcomes and Measures: The primary outcome was patient-reported naloxone acquisition, carrying, and use. Descriptive statistics were used to summarize patient demographic characteristics., Results: Of 205 eligible patients, 41 (20.0%) completed the survey; of those patients, the mean (SD) age was 39.5 (13.7) years, and 21 (51.2%) were women. Fifteen (36.6%) had a personal history of being given naloxone after an overdose. As indicated by the ED record, 27 participants (65.9%) had naloxone dispensed in the ED, and 36 (87.8%) self-reported acquiring naloxone during or after their ED visit. Twenty-four participants (58.5%) were not carrying naloxone in the week before their ED visit. Twenty participants (48.8%) were carrying naloxone after the ED visit, and 27 (65.9%) reported planning to continue carrying naloxone in the future. Of the 24 individuals (58.5%) not carrying naloxone before their ED encounter, 13 (54.2%) reported planning to continue carrying naloxone in the future., Conclusions and Relevance: In this cohort study of adult patients dispensed or prescribed naloxone from the ED, most reported acquiring naloxone on or after discharge. The ED remains a key point of access to naloxone for individuals at high risk of opioid use and overdose, and text messaging could be a method to engage and motivate patient-reported behaviors in enhancing naloxone acquisition and carrying.