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BACKGROUND: The association between cost-sharing and receipt of medication for opioid use disorder (MOUD) is unknown. METHODS: We constructed a cohort of 10,513 commercially insured individuals with a new diagnosis of opioid use disorder (OUD) and information on insurance cost-sharing in a large national de-identified claims database. We examined four cost-sharing measures: 1) pharmacy deductible; 2) medical service deductible; 3) pharmacy medication co-pay; and 4) medical office co-pay. We measured MOUD (naltrexone, buprenorphine, or methadone) initiation (within 14 days of diagnosis), engagement (second receipt within 34 days of first), and 6-month retention (continuous receipt without 14-day gap). We used multivariable logistic regression to assess the association between cost-sharing and MOUD initiation, engagement, and retention. We calculated total out-of-pocket costs in the 30 days following MOUD initiation for each type of MOUD. RESULTS: Of 10,513 individuals with incident OUD, 1,202 (11%) initiated MOUD, 742 (7%) engaged, and 253 (2%) were retained in MOUD at six months. A high ($1,000+) medical deductible was associated with a lower odds of initiation compared to no deductible (odds ratio: 0.85, 95% CI: 0.74-0.98). We found no significant associations between other cost-sharing measures for initiation, engagement, or retention. Median initial 30-day out-of-pocket costs ranged from $100 for methadone to $710 for extended-release naltrexone. CONCLUSION: Among insurance plan cost-sharing measures, only medical services deductible showed an association with decreased MOUD initiation. Policy and benefit design should consider ways to reduce cost barriers to initiation and retention in MOUD.

Objectives. To examine trends in opioid overdose deaths by race/ethnicity from 2018 to 2019 across 67 HEALing Communities Study (HCS) communities in Kentucky, New York, Massachusetts, and Ohio. Methods. We used state death certificate records to calculate opioid overdose death rates per 100 000 adult residents of the 67 HCS communities for 2018 and 2019. We used Poisson regression to calculate the ratio of 2019 to 2018 rates. We compared changes by race/ethnicity by calculating a ratio of rate ratios (RRR) for each racial/ethnic group compared with non-Hispanic White individuals. Results. Opioid overdose death rates were 38.3 and 39.5 per 100 000 for 2018 and 2019, respectively, without a significant change from 2018 to 2019 (rate ratio = 1.03; 95% confidence interval [CI] = 0.98, 1.08). We estimated a 40% increase in opioid overdose death rate for non-Hispanic Black individuals (RRR = 1.40; 95% CI = 1.22, 1.62) relative to non-Hispanic White individuals but no change among other race/ethnicities. Conclusions. Overall opioid overdose death rates have leveled off but have increased among non-Hispanic Black individuals. Public Health Implications. An antiracist public health approach is needed to address the crisis of opioid-related harms. (Am J Public Health. 2021;111(10):1851–1854. https://doi.org/10.2105/AJPH.2021.306431 )

Urine drug testing (UDT) is a recommended risk mitigation strategy for patients prescribed opioids for chronic pain, but evidence that UDT supports identification of substance misuse is limited. Identify the prevalence of UDT results that may identify substance misuse, including diversion, among patients prescribed opioids for chronic pain. Retrospective cohort study. Patients (n=638) receiving opioids for chronic pain who had one or more UDTs, examining up to eight substances per sample, during a one 1-year period. Experts adjudicated the clinical concern that UDT results suggest substance misuse or diversion as not concerning, uncertain, or concerning. Of 638 patients, 48% were female and 49% were over age 55 years. Patients had a median of three UDTs during the intervention year. We identified 37% of patients (235/638) with ≥1 concerning UDT and a further 35% (222/638) having ≥1 uncertain UDT. We found concerning UDTs due to non-detection of a prescribed substance in 24% (156/638) of patients and detection of a non-prescribed substance in 23% (147/638). Compared to patients over 65 years, those aged 18–34 years were more likely to have concerning UDT results with an adjusted odds ratio (AOR) of 4.8 (95% confidence interval [CI] 1.9–12.5). Patients with mental health diagnoses (AOR 1.6 [95% CI 1.1–2.3]) and substance use diagnoses (AOR 2.3 [95% CI 1.5–3.7]) were more likely to have a concerning UDT result. Expert adjudication of UDT results identified clinical concern for substance misuse in 37% of patients receiving opioids for chronic pain. Further research is needed to determine if UDTs impact clinical practice or patient-related outcomes.

People with mental illnesses and people living in poverty have higher rates of incarceration than others, but relatively little is known about the long-term impact that incarceration has on an individual's mental health later in life.To evaluate prior incarceration's association with mental health at midlife.Retrospective cohort study PARTICIPANTS: Participants from the National Longitudinal Survey of Youth 1979 (NLSY79)-a nationally representative age cohort of individuals 15 to 22 years of age in 1979-who remained in follow-up through age 50.Midlife mental health outcomes were measured as part of a health module administered once participants reached 50 years of age (2008-2019): any mental health history, any depression history, past-year depression, severity of depression symptoms in the past 7 days (Center for Epidemiologic Studies Depression [CES-D] scale), and mental health-related quality of life in the past 4 weeks (SF-12 Mental Component Score [MCS]). The main exposure was any incarceration prior to age 50.Among 7889 participants included in our sample, 577 (5.4%) experienced at least one incarceration prior to age 50. Prior incarceration was associated with a greater likelihood of having any mental health history (predicted probability 27.0% vs. 16.6%; adjusted odds ratio [aOR] 1.9 [95%CI: 1.4, 2.5]), any history of depression (22.0% vs. 13.3%; aOR 1.8 [95%CI: 1.3, 2.5]), past-year depression (16.9% vs. 8.6%; aOR 2.2 [95%CI: 1.5, 3.0]), and high CES-D score (21.1% vs. 15.4%; aOR 1.5 [95%CI: 1.1, 2.0]) and with a lower (worse) SF-12 MCS (-2.1 points [95%CI: -3.3, -0.9]; standardized mean difference -0.24 [95%CI: -0.37, -0.10]) at age 50, when adjusting for early-life demographic, socioeconomic, and behavioral factors.Prior incarceration was associated with worse mental health at age 50 across five measured outcomes. Incarceration is a key social-structural driver of poor mental health.

Background Opioid-related overdose mortality has remained at crisis levels across the United States, increasing 5-fold and worsened during the COVID-19 pandemic. The ability to provide forecasts of opioid-related mortality at granular geographical and temporal scales may help guide preemptive public health responses. Current forecasting models focus on prediction on a large geographical scale, such as states or counties, lacking the spatial granularity that local public health officials desire to guide policy decisions and resource allocation. Objective The overarching objective of our study was to develop Bayesian spatiotemporal dynamic models to predict opioid-related mortality counts and rates at temporally and geographically granular scales (ie, ZIP Code Tabulation Areas [ZCTAs]) for Massachusetts. Methods We obtained decedent data from the Massachusetts Registry of Vital Records and Statistics for 2005 through 2019. We developed Bayesian spatiotemporal dynamic models to predict opioid-related mortality across Massachusetts’ 537 ZCTAs. We evaluated the prediction performance of our models using the one-year ahead approach. We investigated the potential improvement of prediction accuracy by incorporating ZCTA-level demographic and socioeconomic determinants. We identified ZCTAs with the highest predicted opioid-related mortality in terms of rates and counts and stratified them by rural and urban areas. Results Bayesian dynamic models with the full spatial and temporal dependency performed best. Inclusion of the ZCTA-level demographic and socioeconomic variables as predictors improved the prediction accuracy, but only in the model that did not account for the neighborhood-level spatial dependency of the ZCTAs. Predictions were better for urban areas than for rural areas, which were more sparsely populated. Using the best performing model and the Massachusetts opioid-related mortality data from 2005 through 2019, our models suggested a stabilizing pattern in opioid-related overdose mortality in 2020 and 2021 if there were no disruptive changes to the trends observed for 2005-2019. Conclusions Our Bayesian spatiotemporal models focused on opioid-related overdose mortality data facilitated prediction approaches that can inform preemptive public health decision-making and resource allocation. While sparse data from rural and less populated locales typically pose special challenges in small area predictions, our dynamic Bayesian models, which maximized information borrowing across geographic areas and time points, were used to provide more accurate predictions for small areas. Such approaches can be replicated in other jurisdictions and at varying temporal and geographical levels. We encourage the formation of a modeling consortium for fatal opioid-related overdose predictions, where different modeling techniques could be ensembled to inform public health policy.

Understanding the factors associated with where people who use opioids live, where their fatal overdoses occur, and where deaths are recorded can improve our knowledge of local risk environments and inform intervention planning. Through geospatial analyses of death certificate data between 2015 and 2017, we found that a majority of opioid-involved fatal overdoses in Massachusetts occurred at home. Age (adjusted odds ratio [AOR], 1.03; 95% confidence interval [CI], 1.02-1.04), living in a census tract with a higher percentage of crowded households (AOR, 1.04; 95% CI, 1.01-1.08), households without vehicles (AOR, 1.01; 95% CI, 1.00-1.02), and Hispanic ethnicity (AOR, 0.56; 95% CI, 0.42-0.74) were independently associated with fatal overdose at home. Using geographically weighted regression, we identified locations where these associations were stronger and could benefit most from home-based and culturally sensitive overdose prevention efforts, including expanded overdose education and naloxone distribution.

BACKGROUND Relative costs of care among treatment options for opioid use disorder (OUD) are unknown. METHODS We identified a cohort of 40,885 individuals with a new diagnosis of OUD in a large national de-identified claims database covering commercially insured and Medicare Advantage enrollees. We assigned individuals to 1 of 6 mutually exclusive initial treatment pathways: (1) Inpatient Detox/Rehabilitation Treatment Center; (2) Behavioral Health Intensive, intensive outpatient or Partial Hospitalization Services; (3) Methadone or Buprenorphine; (4) Naltrexone; (5) Behavioral Health Outpatient Services, or; (6) No Treatment. We assessed total costs of care in the initial 90 day treatment period for each strategy using a differences in differences approach controlling for baseline costs. RESULTS Within 90 days of diagnosis, 94.8% of individuals received treatment, with the initial treatments being: 15.8% for Inpatient Detox/Rehabilitation Treatment Center, 4.8% for Behavioral Health Intensive, Intensive Outpatient or Partial Hospitalization Services, 12.5% for buprenorphine/methadone, 2.4% for naltrexone, and 59.3% for Behavioral Health Outpatient Services. Average unadjusted costs increased from $3250 per member per month (SD $7846) at baseline to $5047 per member per month (SD $11,856) in the 90 day follow-up period. Compared with no treatment, initial 90 day costs were lower for buprenorphine/methadone [Adjusted Difference in Differences Cost Ratio (ADIDCR) 0.65; 95% confidence interval (CI), 0.52-0.80], naltrexone (ADIDCR 0.53; 95% CI, 0.42-0.67), and behavioral health outpatient (ADIDCR 0.54; 95% CI, 0.44-0.66). Costs were higher for inpatient detox (ADIDCR 2.30; 95% CI, 1.88-2.83). CONCLUSION Improving health system capacity and insurance coverage and incentives for outpatient management of OUD may reduce health care costs.

OBJECTIVES: To determine how commonly medical inpatients with opioid use disorder (OUD) referred for post-acute medical care were rejected due to substance use or treatment with opioid agonist therapy (OAT). Additionally, to assess for changes in rejection rates following the United States Attorney’s May 2018 settlement with a Massachusetts nursing facility for violating anti-discrimination laws for such rejections. METHODS: We linked electronic referrals to private Massachusetts post-acute medical care facilities from Boston Medical Center in 2018 with clinical data. We included referrals with evidence of OUD using ICD-10 diagnosis codes or OAT receipt. We identified the frequency of referrals where the stated rejection reason was substance use or OAT and classified these as discriminatory. We used segmented regression to assess for changes in proportion of referrals with substance use and OAT-related rejections before and after the settlement. RESULTS: In 2018, 219 OUD-associated hospitalizations resulted in 1648 referrals to 285 facilities; 81.8% (1348) were rejected. Among hospitalizations, 37.4% (82) received at least one discriminatory rejection. Among rejections, 15.1% (203) were discriminatory (105 for OAT and 98 for substance use). Among facilities, 29.1% (83) had at least one discriminatory rejection. We found no differences in proportion of discriminatory rejections before and after the settlement. CONCLUSIONS: Individuals hospitalized with OUD frequently experience explicit discrimination when rejected from post-acute care despite federal and state protections. Efforts are needed to enhance enforcement of anti-discrimination laws, regulations, and policies to ensure access to post-acute medical care for people with OUD and ongoing medical needs.

IMPORTANCE: Vitamin D deficiency is associated with chronic pain syndromes and higher opioid use among cancer patients, but its association with opioid use among opioid-naïve subjects following a major surgical procedure with acute pain has not been explored. OBJECTIVE: To determine the association between serum 25-hydroxyvitamin D (25(OH)D) levels, opioid use, and opioid use disorder. METHODS: We identified commercially insured subjects aged 18–64 years with available perioperative serum 25-hydroxyvitamin D (25D) levels who underwent one of nine major surgical procedures in 2000–2014. Primary outcomes were dose and duration of opioid use measured using pharmacy claims. Secondary outcome was opioid use disorder captured using diagnosis codes. Multivariable negative binomial models with generalized estimating equations were performed examining the association between 25D levels and postoperative opioid use measures, adjusting for age, sex, race/ethnicity, Charlson score, education, income, latitude, and season of blood draw. Adjusted Cox regression was used to examine the association with opioid use disorder. RESULTS: Among 5446 subjects, serum 25(OH)D was sufficient (≥ 20 ng/mL) among 4349 (79.9%) subjects, whereas 837 (15.4%) had insufficient (12 to

Background and aim Medically managed opioid withdrawal (detox) can increase the risk of subsequent opioid overdose. We assessed the association between mortality following detox and receipt of medications for opioid use disorder (MOUD) and residential treatment after detox. Design Cohort study generated from individually linked public health data sets. Setting Massachusetts, USA. Participants A total of 30 681 opioid detox patients with 61 819 detox episodes between 2012 and 2014. Measurements Treatment categories included no post-detox treatment, MOUD, residential treatment or both MOUD and residential treatment identified at monthly intervals. We classified treatment exposures in two ways: (a) 'on-treatment' included any month where a treatment was received and (b) 'with-discontinuation' individuals were considered exposed through the month following treatment discontinuation. We conducted multivariable Cox proportional hazards analyses and extended Kaplan-Meier estimator cumulative incidence for all-cause and opioid-related mortality for the treatment categories as monthly time-varying exposure variables. Findings Twelve months after detox, 41% received MOUD for a median of 3 months, 35% received residential treatment for a median of 2 months and 13% received both for a median of 5 months. In on-treatment analyses for all-cause mortality compared with no treatment, adjusted hazard ratios (AHR) were 0.34 [95% confidence interval (CI) = 0.27-0.43] for MOUD, 0.63 (95% CI = 0.47-0.84) for residential treatment and 0.11 (95% CI = 0.03-0.43) for both. In with-discontinuation analyses for all-cause mortality, compared with no treatment, AHRs were 0.52 (95% CI = 0.42-0.63) for MOUD, 0.76 (95% CI = 0.59-0.96) for residential treatment and 0.21 (95% CI = 0.08-0.55) for both. Results were similar for opioid-related overdose mortality. Conclusions Among people who have undergone medically managed opioid withdrawal, receipt of medications for opioid use disorder, residential treatment or the combination of medications for opioid use disorder and residential treatment were associated with substantially reduced mortality compared with no treatment.

Key Points Questions Is exposure to incarceration associated with a long-term increase in mortality rate, and does this association differ by race? Findings In this cohort study of 7974 individuals who were followed up from 1979 to 2018, incarceration was associated with a 65% higher mortality rate among Black participants. Among non-Black participants, incarceration was not associated with mortality. Meaning These findings suggest that racial disparities in the association of incarceration with mortality—as well as in rates of exposure to incarceration—may partially explain the lower life expectancy of the non-Hispanic Black population in the US., This cohort study assesses whether incarceration during adulthood is associated with a higher mortality rate and whether this association differs by race., Importance The association between incarceration and long-term mortality risk is unknown and may contribute to racial disparities in overall life expectancy. Objective To determine whether incarceration in the US is associated with an increase in mortality risk and whether this association is different for Black compared with non-Black populations. Design, Setting, and Participants This generational retrospective cohort study used data from the National Longitudinal Survey of Youth 1979, a nationally representative cohort of noninstitutionalized youths aged 15 to 22 years, from January 1 to December 31, 1979, with follow-up through December 31, 2018. A total of 7974 non-Hispanic Black and non-Hispanic non-Black participants were included. Statistical analysis was performed from October 26, 2019, to August 31, 2021. Exposures Time-varying exposure of having experienced incarceration during follow-up. Main Outcomes and Measures The main outcome was time to death. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs, adjusted for baseline sociodemographic, economic, and behavioral risk factors. Models were evaluated for the full cohort and stratified by race. Results Of the 7974 individuals included in our sample, 4023 (50.5%) were male, and 2992 (37.5%) identified as Black (median age, 18 [IQR, 17-20] years). During a median follow-up of 35 years (IQR, 33-37 years), 478 participants were incarcerated and 818 died. Unadjusted exposure to at least 1 incarceration between 22 and 50 years of age was 11.5% (95% CI, 10.4%-12.7%) for Black participants compared with 2.5% (95% CI, 2.1%-2.9%) for non-Black participants. In the multivariable Cox proportional hazards model with the full cohort, time-varying exposure to incarceration was associated with an increased mortality rate (adjusted HR [aHR], 1.35; 95% CI, 0.97-1.88), a result that was not statistically significant. In the models stratified by race, incarceration was significantly associated with increased mortality among Black participants (aHR, 1.65; 95% CI, 1.18-2.31) but not among non-Black participants (aHR, 1.17; 95% CI, 0.68-2.03). Conclusions and Relevance In this cohort study with 4 decades of follow-up, incarceration was associated with a higher mortality rate among Black participants but not among non-Black participants. These findings suggest that incarceration, which was prevalent and unevenly distributed, may have contributed to the lower life expectancy of the non-Hispanic Black population in the US.

IMPORTANCE: Opioid-related mortality and national prescribing guidelines have led to tapering of doses among patients prescribed long-term opioid therapy for chronic pain. There is limited information about risks related to tapering, including overdose and mental health crisis. OBJECTIVE: To assess whether there are associations between opioid dose tapering and rates of overdose and mental health crisis among patients prescribed stable, long-term, higher-dose opioids. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using deidentified medical and pharmacy claims and enrollment data from the OptumLabs Data Warehouse from 2008 to 2019. Adults in the US prescribed stable higher doses (mean ≥50 morphine milligram equivalents/d) of opioids for a 12-month baseline period with at least 2 months of follow-up were eligible for inclusion. EXPOSURES: Opioid tapering, defined as at least 15% relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period. Maximum monthly dose reduction velocity was computed during the same period. MAIN OUTCOMES AND MEASURES: Emergency or hospital encounters for (1) drug overdose or withdrawal and (2) mental health crisis (depression, anxiety, suicide attempt) during up to 12 months of follow-up. Discrete time negative binomial regression models estimated adjusted incidence rate ratios (aIRRs) of outcomes as a function of tapering (vs no tapering) and dose reduction velocity. RESULTS: The final cohort included 113 618 patients after 203 920 stable baseline periods. Among the patients who underwent dose tapering, 54.3% were women (vs 53.2% among those who did not undergo dose tapering), the mean age was 57.7 years (vs 58.3 years), and 38.8% were commercially insured (vs 41.9%). Posttapering patient periods were associated with an adjusted incidence rate of 9.3 overdose events per 100 person-years compared with 5.5 events per 100 person-years in nontapered periods (adjusted incidence rate difference, 3.8 per 100 person-years [95% CI, 3.0-4.6]; aIRR, 1.68 [95% CI, 1.53-1.85]). Tapering was associated with an adjusted incidence rate of 7.6 mental health crisis events per 100 person-years compared with 3.3 events per 100 person-years among nontapered periods (adjusted incidence rate difference, 4.3 per 100 person-years [95% CI, 3.2-5.3]; aIRR, 2.28 [95% CI, 1.96-2.65]). Increasing maximum monthly dose reduction velocity by 10% was associated with an aIRR of 1.09 for overdose (95% CI, 1.07-1.11) and of 1.18 for mental health crisis (95% CI, 1.14-1.21). CONCLUSIONS AND RELEVANCE: Among patients prescribed stable, long-term, higher-dose opioid therapy, tapering events were significantly associated with increased risk of overdose and mental health crisis. Although these findings raise questions about potential harms of tapering, interpretation is limited by the observational study design.

Opioid dosage tapering has emerged as a strategy to reduce harms associated with long-term opioid therapy; however, evidence supporting this approach is limited.To identify the association of opioid tapering or abrupt discontinuation with opioid overdose and suicide events among patients receiving stable long-term opioid therapy without evidence of opioid misuse.This comparative effectiveness study with a trial emulation approach used a large US claims data set of individuals with commercial insurance or Medicare Advantage who were aged 18 years or older and receiving stable long-term opioid therapy without evidence of opioid misuse between January 1, 2010, and December 31, 2018. Statistical analysis was performed from January 17, 2020, through November 12, 2021.Three opioid dosage strategies: stable dosage, tapering (dosage reduction ≥15%), or abrupt discontinuation.Time to opioid overdose or suicide event identified from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes in medical claims over 11 months of follow-up. Inverse probability weighting was used to adjust for baseline confounders. The primary analysis used an intention-to-treat approach; follow-up after assignment regardless of changes in opioid dose was included. A per-protocol analysis was also conducted, in which episodes were censored for lack of adherence to assigned treatment.A cohort of 199 836 individuals (45.1% men; mean [SD] age, 56.9 [12.4] years; and 57.6% aged 45-64 years) had 415 123 qualifying, long-term opioid therapy episodes; 87.1% of episodes were considered stable, 11.1% were considered a taper, and 1.8% were considered abrupt discontinuation. The adjusted cumulative incidence of opioid overdose or suicide events 11 months after baseline was 0.96% (95% CI, 0.92%-0.99%) with a stable dosage strategy, 1.10% (95% CI, 0.99%-1.22%) with a tapered dosage strategy, and 1.28% (95% CI, 0.93%-1.38%) with an abrupt discontinuation strategy. The risk difference between a taper and a stable dosage was 0.15% (95% CI, 0.03%-0.26%), and the risk difference between abrupt discontinuation and a stable dosage was 0.33% (95% CI, -0.03% to 0.74%). Results were similar using the per-protocol approach.This study identified a small absolute increase in risk of harms associated with opioid tapering compared with a stable opioid dosage. These results do not suggest that policies of mandatory dosage tapering for individuals receiving a stable long-term opioid dosage without evidence of opioid misuse will reduce short-term harm via suicide and overdose.

OBJECTIVES Widespread use and misuse of prescription and illicit opioids have exposed millions to health risks including serious infectious complications. Little is known, however, about the association between opioid use and sepsis. DESIGN Retrospective cohort study. SETTING About 373 U.S. hospitals. PATIENTS Adults hospitalized between January 2009 and September 2015. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Sepsis was identified by clinical indicators of concurrent infection and organ dysfunction. Opioid-related hospitalizations were identified by the International Classification of Diseases, 9th Revision, Clinical Modification codes and/or inpatient orders for buprenorphine. Clinical characteristics and outcomes were compared by sepsis and opioid-related hospitalization status. The association between opioid-related hospitalization and all-cause, in-hospital mortality in patients with sepsis was assessed using mixed-effects logistic models to adjust for baseline characteristics and severity of illness.The cohort included 6,715,286 hospitalizations; 375,479 (5.6%) had sepsis, 130,399 (1.9%) had opioid-related hospitalizations, and 8,764 (0.1%) had both. Compared with sepsis patients without opioid-related hospitalizations (n = 366,715), sepsis patients with opioid-related hospitalizations (n = 8,764) were younger (mean 52.3 vs 66.9 yr) and healthier (mean Elixhauser score 5.4 vs 10.5), had more bloodstream infections from Gram-positive and fungal pathogens (68.9% vs 47.0% and 10.6% vs 6.4%, respectively), and had lower in-hospital mortality rates (10.6% vs 16.2%; adjusted odds ratio, 0.73; 95% CI, 0.60-0.79; p < 0.001 for all comparisons). Of 1,803 patients with opioid-related hospitalizations who died in-hospital, 928 (51.5%) had sepsis. Opioid-related hospitalizations accounted for 1.5% of all sepsis-associated deaths, including 5.7% of sepsis deaths among patients less than 50 years old. From 2009 to 2015, the proportion of sepsis hospitalizations that were opioid-related increased by 77% (95% CI, 40.7-123.5%). CONCLUSIONS Sepsis is an important cause of morbidity and mortality in patients with opioid-related hospitalizations, and opioid-related hospitalizations contribute disproportionately to sepsis-associated deaths among younger patients. In addition to ongoing efforts to combat the opioid crisis, public health agencies should focus on raising awareness about sepsis among patients who use opioids and their providers.

INTRODUCTION: Medications for opioid use disorder (MOUD) are highly effective, but barriers along the cascade of care for opioid use disorder (OUD) from diagnosis to treatment limit their reach. For individuals desiring MOUD, the final step in the cascade is filling a written prescription, and fill rates have not been described. METHODS: We used data from a large de-identified database linking individuals’ electronic medical records (EMR) and administrative claims data and employed a previously developed algorithm to identify individuals with a new diagnosis of OUD. We included individuals with a prescription for buprenorphine or naltrexone recorded in the EMR. The outcome was a prescription fill within 30 days as reported in claims data. We compared demographic and clinical characteristics between those who did and did not fill the prescription and used a Kaplan-Meier curve to assess whether fill rates differed based on patient copay. RESULTS: We identified 264 individuals with a new diagnosis of OUD who had a prescription written for buprenorphine or oral naltrexone. Of these, 70% (184) filled the prescription within 30 days, and more than half (57%) filled the prescription on the day it was written. Individuals with prescription copay at or below the mean had a 75% fill rate at 30 days compared with 63% for those with copay above the mean (p

Objectives: Opioid-related overdoses are commonly attributed to prescription opioids. We examined data on opioid-related overdose decedents in Massachusetts. For each decedent, we determined which opioid medications had been prescribed and dispensed and which opioids were detected in postmortem medical examiner toxicology specimens. Methods: Among opioid-related overdose decedents in Massachusetts during 2013-2015, we analyzed individually linked postmortem opioid toxicology reports and prescription drug monitoring program records to determine instances of overdose in which a decedent had a prescription active on the date of death for the opioid(s) detected in the toxicology report. We also calculated the proportion of overdoses for which prescribed opioid medications were not detected in decedents’ toxicology reports. Results: Of 2916 decedents with complete toxicology reports, 1789 (61.4%) had heroin and 1322 (45.3%) had fentanyl detected in postmortem toxicology reports. Of the 491 (16.8%) decedents with ≥1 opioid prescription active on the date of death, prescribed opioids were commonly not detected in toxicology reports, specifically: buprenorphine (56 of 97; 57.7%), oxycodone (93 of 176; 52.8%), and methadone prescribed for opioid use disorder (36 of 112; 32.1%). Only 39 (1.3%) decedents had an active prescription for each opioid detected in toxicology reports on the date of death. Conclusion: Linking overdose toxicology reports to prescription drug monitoring program records can help attribute overdoses to prescribed opioids, diverted prescription opioids, heroin, and illicitly made fentanyl.

Background and aims While prescribed and illicit opioid use are primary drivers of the national surges in overdose deaths, opioid overdose deaths in which stimulants are also present are increasing in the U.S. We determined the social determinants and sociodemographic factors associated with opioid-only versus polysubstance opioid overdose deaths in Massachusetts. Particular attention was focused on the role of stimulants in opioid overdose deaths. Methods We analyzed all opioid-related overdose deaths from 2014 to 2015 in an individually-linked population database in Massachusetts. We used linked postmortem toxicology data to identify drugs present at the time of death. We constructed a multinomial logistic regression model to identify factors associated with three mutually exclusive overdose death groups based on toxicological results: opioid-related deaths with (1) opioids only present, (2) opioids and other substances not including stimulants, and (3) opioids and stimulants with or without other substances. Results Between 2014 and 2015, there were 2,244 opioid-related overdose deaths in Massachusetts that had accompanying toxicology results. Toxicology reports indicated that 17% had opioids only, 36% had opioids plus stimulants, and 46% had opioids plus another non-stimulant substance. Persons older than 24 years, non-rural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone. Conclusions Polysubstance opioid overdose is increasingly common in the US. Addressing modifiable social determinants of health, including barriers to mental health services and homelessness, is important to reduce polysubstance use and overdose deaths.

Although HIV preexposure prophylaxis (PrEP) implementation among persons who inject drugs has been inadequate, national HIV monitoring programs do not include data on PrEP, and specific trends in PrEP use are not well understood.To estimate HIV PrEP uptake among commercially insured persons with opioid or stimulant use disorder by injection drug use (IDU) status.This cross-sectional study used deidentified data from the MarketScan Commercial Claims and Encounters Database to identify a sample of 547 709 commercially insured persons without HIV but with opioid and/or stimulant use disorder, including 110 592 with evidence of IDU between January 1, 2010, and December 31, 2019. Data were analyzed from November 1, 2020, to July 1, 2021.Persons with opioid and/or stimulant use disorder and evidence of IDU were identified through claims data.The outcome was receipt of tenofovir disoproxil fumarate and emtricitabine for PrEP as identified from filled pharmacy claims. Multivariable logistic regression was used to assess the association of demographic and clinical characteristics with receipt of PrEP.The study cohort included 211 609 (28.6%) females and 336 100 (61.4%) males with a combined mean (SD) age of 34.8 (13.1) years, including 110 592 individuals with evidence of IDU. During the study period, 508 (0.09%) persons with opioid and/or stimulant use disorder, including 170 (0.15%) with evidence of IDU, received PrEP. Receipt of PrEP increased from 0.001 to 0.243 per 100 person-years from 2010 through 2019 among the entire cohort and from 0.000 to 0.295 per 100 person-years among those with IDU. In multivariable analysis, PrEP use was more likely among males (adjusted odds ratio [aOR] 8.72; 95% CI, 6.39-11.89), persons with evidence of IDU (aOR, 1.47; 95% CI, 1.21-1.79), and persons with evidence of sexual risk indications for PrEP (aOR, 23.68; 95% CI, 19.57-28.66).In this cross-sectional study of commercially insured persons with opioid and/or stimulant use disorder, HIV PrEP delivery remained low, including among those with evidence of IDU. PrEP should be consistently offered alongside substance use disorder treatment and other harm reduction and HIV prevention services.

Objectives. To estimate the annual prevalence of opioid use disorder (OUD) in Massachusetts from 2011 to 2015. Methods. We performed a multisample stratified capture–recapture analysis to estimate OUD prevalence in Massachusetts. Individuals identified from 6 administrative databases for 2011 to 2012 and 7 databases for 2013 to 2015 were linked at the individual level and included in the analysis. Individuals were stratified by age group, sex, and county of residence. Results. The OUD prevalence in Massachusetts among people aged 11 years or older was 2.72% in 2011 and 2.87% in 2012. Between 2013 and 2015, the prevalence increased from 3.87% to 4.60%. The greatest increase in prevalence was observed among those in the youngest age group (11–25 years), a 76% increase from 2011 to 2012 and a 42% increase from 2013 to 2015. Conclusions. In Massachusetts, the OUD prevalence was 4.6% among people 11 years or older in 2015. The number of individuals with OUD is likely increasing, particularly among young people.

INTRODUCTION In response to the opioid overdose crisis, providers were urged to taper and discontinue patients from long-term opioid therapy; however, abrupt discontinuation may lead to poor health outcomes. This study aims to determine abrupt and tapered discontinuation rates and identify the patient and provider characteristics associated with abrupt discontinuation. METHODS Data were from the Massachusetts Prescription Monitoring Program, 2015-2018. Patients discontinued from long-term opioid therapy were included in the analysis. Differences between abrupt and tapered discontinuations were identified with bivariate correlations, and variables independently associated with abrupt discontinuation were identified using multivariable Poisson regression analyses. Data were analyzed during 2019-2021. RESULTS In total, 277,485 patients experienced 359,320 discontinuations, of which 33.7% (n=120,964) were abrupt. Of all discontinuations, 55.7% were among female patients, and 57.9% were among patients aged >55 years. The ratio of abrupt to tapered discontinuations increased from 1:2.11 in 2015 to 1:1.75 in 2018. In bivariate analysis, prescribers with more patients receiving monthly opioid prescriptions were less likely to abruptly discontinue patients (29.0, IQR=13.9, 55.3 vs 18.8, IQR=5.84, 43.9, p

Objective To determine HIV testing trends during emergency department (ED) visits among those with and without substance use disorder (SUD) and examine factors associated with test receipt. Methods We identified individuals age ≥ 15 with an ED visit between 2014 and 2018 in the National Hospital Ambulatory Medical Care Survey (NHAMCS), a representative sample of United States ED visits. We examined HIV testing trends by SUD status and used multivariable logistic regression accounting for NHAMCS's complex survey design to identify factors associated with HIV testing. Results We identified 6399 SUD and 75,498 non-SUD ED visits. Of SUD visits, 1.4% [95% Confidence Interval (95%CI 0.9–1.9)] resulted in HIV testing compared to 0.6% (95%CI 0.4–0.7) of non-SUD visits. During the second half of the study (Q3, 2016 - Q4, 2018), HIV testing increased from 1.1% (95%CI 0.6–1.6) to 1.7% (95%CI 1.0–2.5) among those with SUD and from 0.5% (95%CI 0.3–0.6) to 0.6% (95%CI 0.5–0.8) among those without SUD. In adjusted models, SUD status was associated with increased odds of HIV testing [Adjusted Odds Ratio (AOR) 1.6 (95%CI 1.1–2.2)]. Those receiving toxicology testing (AOR 2.2, 95%CI 1.6–3.2), Black (AOR 3.6, 95%CI 2.6–4.9) and Hispanic people (AOR 2.7, 95%CI 1.9–3.7), insured by Medicaid (AOR 1.6, 95%CI 1.2–2.2) or self-pay (AOR 1.7, 95%CI 1.1–2.8), and with venipuncture (AOR 3.0, 95%CI 2.2–4.1) also had greater odds of HIV testing. Conclusion HIV testing in the ED was rare, but slightly more common in individuals with SUD. Efforts to increase ED HIV testing among people with SUD are needed.

Background Efforts to address opioid-involved overdose fatalities have led to widespread implementation of various initiatives to taper (i.e., reduce or discontinue) opioid prescriptions despite a limited understanding of patients’ experience. Methods From 2019–2020, we recruited patients with chronic, non-cancer pain who had undergone a reduction in opioid daily dosage of ≥50 % in the past two years at Boston Medical Center or Michigan Medicine. Participants completed semi-structured interviews exploring health history, opioid use, and taper experiences. Inductive analysis, guided by theoretical conceptualizations of structural stigma, identified emergent themes. Results Among 41 participants, three elements of structural stigma were identified across participants’ lives. First, participants identified themselves as overlooked subjects of the U.S. opioid crisis, who experienced overprescribing, subsequent stigmatization and surveillance of opioid use (e.g., toxicology screening, “pill counts”), and various tapering initiatives. Second, during the course of pain treatment, participants felt stigmatized and invalidated by cultural norms linking chronic pain to stereotypes of acting disingenuously (e.g., “drug-seeking”). Finally, during and after tapers, institutional policies and programs further increased participants’ feelings of marginalization, producing multiple unintended consequences, including reduced access to medical care and feeling “orphaned by the system.” Conclusions Opioid tapers may exacerbate the social production and burden of stigma among patients with chronic pain, especially when processes are perceived to invalidate pain, endorse stereotypes, and label previously effective, acceptable treatment as inappropriate. Findings highlight how various tapering initiatives reinforce the devalued status of people living with chronic pain while also reducing patients’ wellbeing and confidence in medical systems.

This cohort study assess the association of receipt of medication for opioid use disorder and mortality after hospitalization for injection drug use–associated infective endocarditis in Massachusetts., Key Points Question Is there an association between receipt of medication for opioid use disorder (MOUD) and mortality after hospitalization for injection drug use–associated infective endocarditis? Findings In this cohort study 679 individuals hospitalized with injection drug use–associated endocarditis, 24% received MOUD within 3 months of discharge. MOUD receipt within 3 months of discharge was not associated with reduced mortality but was associated with a reduction in mortality in the month received. Meaning In this study, treatment with MOUD was uncommon and was associated with reduced mortality in the time-varying analysis but not the main analysis, possibly owing to poor treatment retention., Importance Although hospitalizations for injection drug use–associated infective endocarditis (IDU-IE) have increased during the opioid crisis, utilization of and mortality associated with receipt of medication for opioid use disorder (MOUD) after discharge from the hospital among patients with IDU-IE are unknown. Objective To assess the proportion of patients receiving MOUD after hospitalization for IDU-IE and the association of MOUD receipt with mortality. Design, Setting, and Participants This retrospective cohort study used a population registry with person-level medical claims, prescription monitoring program, mortality, and substance use treatment data from Massachusetts between January 1, 2011, and December 31, 2015; IDU-IE–related discharges between July 1, 2011, and June, 30, 2015, were analyzed. All Massachusetts residents aged 18 to 64 years with a first hospitalization for IDU-IE were included; IDU-IE was defined as any hospitalization with a diagnosis of endocarditis and at least 1 claim in the prior 6 months for OUD, drug use, or hepatitis C and with 2-month survival after hospital discharge. Data were analyzed from November 11, 2018, to June 23, 2020. Exposure Receipt of MOUD, defined as any treatment with methadone, buprenorphine, or naltrexone, within 3 months after hospital discharge excluding discharge month for IDU-IE. Main Outcomes and Measures The main outcome was all-cause mortality. The proportion of patients who received MOUD in the 3 months after hospital discharge was calculated. Multivariable Cox proportional hazard regression models were used to examine the association of MOUD receipt with mortality, adjusting for sex, age, medical and psychiatric comorbidities, and homelessness. In the secondary analysis, receipt of MOUD was considered as a monthly time-varying exposure. Results Of 679 individuals with IDU-IE, 413 (60.8%) were male, the mean (SD) age was 39.2 (12.1) years, 298 (43.9%) were aged 18 to 34 years, 419 (72.3) had mental illness, and 209 (30.8) experienced homelessness. A total of 134 individuals (19.7%) received MOUD in the 3 months before hospitalization and 165 (24.3%) in the 3 months after hospital discharge. Of those who received MOUD after discharge, 112 (67.9%) received buprenorphine. The crude mortality rate was 9.2 deaths per 100 person-years. MOUD receipt within 3 months after discharge was not associated with reduced mortality (adjusted hazard ratio, 1.29; 95% CI, 0.61-2.72); however, MOUD receipt was associated with reduced mortality in the month that MOUD was received (adjusted hazard ratio, 0.30; 95% CI, 0.10-0.89). Conclusions and Relevance In this cohort study, receipt of MOUD was associated with reduced mortality after hospitalization for injection drug use–associated endocarditis only in the month it was received. Efforts to improve MOUD initiation and retention after IDU-IE hospitalization may be beneficial.

Objectives Opioid overdose deaths in Massachusetts linked to illicitly-manufactured fentanyl have increased dramatically. In response, an urban safety-net hospital added urine fentanyl testing with reflex confirmation testing to its standard urine toxicology panel. The goals of this study were to describe fentanyl toxicology test results, identify the positive predictive value of presumptive fentanyl immunoassay, and describe co-substance use among those with unexpected fentanyl positive results. Methods We included urine toxicology tests from January through June 2016 analyzed at an urban safety-net hospital. We excluded tests from individuals prescribed or administered fentanyl within the preceding 72 hours. Positive fentanyl immunoassay tests underwent reflex chromatography confirmation testing. Samples that confirmed positive for acetyl fentanyl and/or fentanyl and/or norfentanyl were considered true positives. Results Of 11,873 urine samples, 10.4% of samples screened fentanyl positive and 8.8% were confirmed fentanyl positive. The positive predictive value of a positive urine fentanyl screen was 85.7%. Of 4398 unique patients, 13.2% had at least 1 test confirmed positive for nonprescription fentanyl. Patients with a confirmed fentanyl positive drug test were more likely to have positive urine drug test for barbiturates, benzodiazepines, cocaine, methadone, and opiates, and less likely to have oxycodone or buprenorphine. Conclusions At an urban safety-net hospital, nonprescription fentanyl use was common and was associated with greater use of other substances favoring routine fentanyl testing. Although the positive predictive value of the screening test was high, confirmation testing detected substantial numbers of false positives, especially in older patients. Therefore, fentanyl confirmation testing should be used when results will change treatment approach and patient education.

BackgroundAmong those with injection drug use-associated infective endocarditis (IDU-IE), against medical advice (AMA) discharge is common and linked to adverse outcomes. Understanding trends, risk factors, and timing is needed to reduce IDU-IE AMA discharges.MethodsWe identified individuals ages 18–64 with International Classification of Diseases, 9thRevision, diagnosis codes for infective endocarditis (IE) in the National Inpatient Sample, a representative sample of United States hospitalizations from January 2010 to September 2015. We plotted unadjusted quarter-year trends for AMA discharges and used multivariable logistic regression to identify factors associated with AMA discharge among IE hospitalizations, comparing IDU-IE with non-IDU-IE.ResultsWe identified 7259 IDU-IE and 23 633 non-IDU-IE hospitalizations. Of these hospitalizations, 14.2% of IDU-IE and 1.9% of non-IDU-IE resulted in AMA discharges. More than 30% of AMA discharges for both groups occurred before hospital day 3. In adjusted models, IDU status (adjusted odds ratio [AOR], 3.92; 95% confidence interval [CI], 3.43–4.48)] was associated with increased odds of AMA discharge. Among IDU-IE, women (AOR, 1.21; 95% CI, 1.04–1.41) and Hispanics (AOR, 1.32; 95% CI, 1.03–1.69) had increased odds of AMA discharge, which differed from non-IDU-IE. Over nearly 6 years, odds of AMA discharge increased 12% per year for IDU-IE (AOR, 1.12; 95% CI, 1.07–1.18) and 6% per year for non-IDU-IE (AOR, 1.06; 95% CI. 1.00–1.13).ConclusionsAMA discharges have risen among individuals with IDU-IE and non-IDE-IE. Among those who inject drugs, AMA discharges were more common and increases sharper. Efforts that address the rising fraction, disparities, and timing of IDU-IE AMA discharges are needed.

Highlights • HEALing Communities Study is a parallel-group cluster randomized controlled trial. • Communities That HEAL intervention’s goal is to reduce opioid overdose deaths. • Structured consensus decision-making strategy guided study measure development. • More than 80 study measure specifications and a common data model were developed. • The study will provide methodology and longitudinal community data for research., Background Opioid overdose deaths remain high in the U.S. Despite having effective interventions to prevent overdose deaths, there are numerous barriers that impede their adoption. The primary aim of the HEALing Communities Study (HCS) is to determine the impact of an intervention consisting of community-engaged, data-driven selection, and implementation of an integrated set of evidence-based practices (EBPs) on reducing opioid overdose deaths. Methods The HCS is a four year multi-site, parallel-group, cluster randomized wait-list controlled trial. Communities (n = 67) in Kentucky, Massachusetts, New York and Ohio are randomized to active intervention (Wave 1), which starts the intervention in Year 1 or the wait-list control (Wave 2), which starts the intervention in Year 3. The HCS will test a conceptually driven framework to assist communities in selecting and adopting EBPs with three components: 1) A community engagement strategy with local coalitions to guide and implement the intervention; 2) A compendium of EBPs coupled with technical assistance; and 3) A series of communication campaigns to increase awareness and demand for EBPs and reduce stigma. An implementation science framework guides the intervention and allows for examination of the multilevel contexts that promote or impede adoption and expansion of EBPs. The primary outcome, number of opioid overdose deaths, will be compared between Wave 1 and Wave 2 communities during Year 2 of the intervention for Wave 1. Numerous secondary outcomes will be examined. Discussion The HCS is the largest community-based implementation study in the field of addiction with an ambitious goal of significantly reducing fatal opioid overdoses.

Objective:In 2012, the US government overhauled school nutrition standards, but few studies have evaluated the effects of these standards at the national level. The current study examines the impact of the updated school nutrition standards on dietary and health outcomes of schoolchildren in a nationally representative data set.Design:Difference-in-differences. We compared weekday fruit and vegetable intake between students with daily school lunch participation and students without school lunch participation before and after implementation of updated school nutrition standards using a multivariable linear regression model. Secondary outcomes included weekday solid fat and added sugar (SoFAS) intake and overweight and obesity prevalence. We adjusted analyses for demographic and family socio-economic factors.Setting:USA.Participants:K-12 students, aged 6–20 years (n 9172), from the National Health and Nutrition Examination Survey, 2005–2016.Results:Implementation of updated school nutrition standards was not associated with a change in weekday fruit and vegetable intake (β = 0·02 cups, 95 % CI −0·23, 0·26) for students with daily school lunch participation. However, implementation of the policy was associated with a 1·5 percentage point (95 % CI −3·0, −0·1) decline in weekday SoFAS intake and a 6·1 percentage point (95 % CI −12·1, −0·1) decline in overweight and obesity prevalence.Conclusions:Changes to US school nutrition standards were associated with reductions in the consumption of SoFAS as well as a decrease in overweight and obesity in children who eat school lunch. However, we did not detect a change in weekday intake of fruits and vegetables associated with the policy change.

This cross-sectional analysis assesses the prevalence and number of alcohol- or benzodiazepine-involved opioid overdose deaths by opioid subtypes in the United States from 1999 to 2017., Key Points Question What is the prevalence of alcohol or benzodiazepine co-involvement in opioid overdose deaths among the opioid subtypes currently and over time? Findings This repeated cross-sectional analysis of deaths attributed to opioid overdose identified the co-involvement of alcohol or benzodiazepines as common and increasing, reaching 14.7% for alcohol and 21.0% for benzodiazepines in 2017. Significant correlations occurred between state-level binge drinking rates and alcohol co-involvement and between state-level benzodiazepine prescribing rates and benzodiazepine co-involvement in opioid overdose deaths. Meaning Prevalence of respiratory-depressing drugs in opioid overdose deaths is common and increasing and represents a potential target for policy and practice efforts to reduce opioid-related harms., Importance The use of benzodiazepines or alcohol together with opioids increases overdose risk, but characterization of co-involvement by predominant opioid subtype is incomplete to date. Understanding the use of respiratory depressants in opioid overdose deaths (OODs) is important for prevention efforts and policy making. Objective To assess the prevalence and number of alcohol- or benzodiazepine-involved OODs by opioid subtypes in the United States from 1999 to 2017. Design and Setting This repeated cross-sectional analysis used data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database of all opioid-involved poisoning deaths from January 1, 1999, to December 31, 2017, for the United States. State-level binge drinking prevalence rates for 2015 to 2017 were obtained from the Behavior Risk Factor Surveillance System of the Centers for Disease Control and Prevention, and benzodiazepine prescribing rates for 2012 (most recent available data) were obtained from IMS Health, a commercial database. Data were analyzed from July 10, 2018, to May 16, 2019. Main Outcomes and Measures Prevalence of alcohol or benzodiazepine co-involvement for all OODs and by opioid subtype, nationally and by state. Results From 1999 to 2017, 399 230 poisoning deaths involved opioids, of which 263 601 (66.0%) were male, and 204 560 (51.2%) were aged 35 to 54 years. Alcohol co-involvement for all opioid overdose deaths increased nonlinearly from 12.4% in 1999 to 14.7% in 2017. By opioid subtype, deaths involving heroin and synthetic opioids (eg, fentanyl; excluding methadone) had the highest alcohol co-involvement at 15.5% and 14.9%, respectively, in 2017. Benzodiazepine co-involvement in all OODs increased nonlinearly from 8.7% in 1999 to 21.0% in 2017. Benzodiazepines were present in 33.1% of prescription OODs and 17.1% of synthetic OODs in 2017. State-level rates of binge drinking were significantly correlated with alcohol co-involvement in all OODs (r = 0.34; P = .02). State benzodiazepine prescribing rates were significantly correlated with benzodiazepine co-involvement in all OODs (r = 0.57; P

Background and aims Benzodiazepines are commonly prescribed to patients with opioid use disorder receiving buprenorphine treatment, yet may increase overdose risk. However, prescribed benzodiazepines may improve retention in care by reducing buprenorphine discontinuation and thus may prevent relapse to illicit opioid use. We aimed to test the association between benzodiazepine prescription and fatal opioid overdose, non-fatal opioid overdose, all-cause mortality and buprenorphine discontinuation. Design and setting This was a retrospective cohort study using five individually linked data sets from Massachusetts, United States government agencies. Participants We studied 63 389 Massachusetts residents aged 18 years or older who received buprenorphine treatment between January 2012 and December 2015. Measurements Filled benzodiazepine prescription during buprenorphine treatment was the main independent variable. The primary outcome was time to fatal opioid overdose. Secondary outcomes were time to non-fatal opioid overdose, all-cause mortality and buprenorphine discontinuation. We defined buprenorphine discontinuation as having a 30-day gap without another prescription following the end date of the previous prescription. We used Cox proportional hazards models to calculate hazards ratios that tested the association between receipt of benzodiazepines and all outcomes, restricted to periods during buprenorphine treatment. Findings Of the 63 345 individuals who received buprenorphine, 24% filled at least one benzodiazepine prescription during buprenorphine treatment. Thirty-one per cent of the 183 deaths from opioid overdose occurred when individuals received benzodiazepines during buprenorphine treatment. Benzodiazepine receipt during buprenorphine treatment was associated with an increased risk of fatal opioid overdose adjusted hazard ratio (HR) = 2.92, 95% confidence interval (CI) = 2.10-4.06, non-fatal opioid overdose, adjusted HR = 2.05, 95% CI, 1.68-2.50, all-cause mortality, adjusted HR = 1.90, 95% CI, 1.48-2.44 and a decreased risk of buprenorphine discontinuation, adjusted HR = 0.87, 95% CI, 0.85-0.89. Conclusions Benzodiazepine receipt appears to be associated with both increased risk of opioid overdose and all-cause mortality and decreased risk of buprenorphine discontinuation among people receiving buprenorphine.

Background Although national syndromic surveillance data reported declines in emergency department (ED) visits after the declaration of the national stay-at-home order for COVID-19, little is known whether these declines were observed for suspected opioid overdose. Methods This interrupted time series study used syndromic surveillance data from four states participating in the HEALing Communities Study: Kentucky, Massachusetts, New York, and Ohio. All ED encounters for suspected opioid overdose (n = 48,301) occurring during the first 31 weeks of 2020 were included. We examined the impact of the national public health emergency for COVID-19 (declared on March 14, 2020) on trends in ED encounters for suspected opioid overdose. Results Three of four states (Massachusetts, New York and Ohio) experienced a statistically significant immediate decline in the rate of ED encounters for suspected opioid overdose (per 100,000) after the nationwide public health emergency declaration (MA: -0.99; 95 % CI: -1.75, -0.24; NY: -0.10; 95 % CI, -0.20, 0.0; OH: -0.33, 95 % CI: -0.58, -0.07). After this date, Ohio and Kentucky experienced a sustained rate of increase for a 13-week period. New York experienced a decrease in the rate of ED encounters for a 10-week period, after which the rate began to increase. In Massachusetts after a significant immediate decline in the rate of ED encounters, there was no significant difference in the rate of change for a 6-week period, followed by an immediate increase in the ED rate to higher than pre-COVID levels. Conclusions The heterogeneity in the trends in ED encounters between the four sites show that the national stay-at-home order had a differential impact on opioid overdose ED presentation in each state.

Objective: A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics. Design: Retrospective cohort study. Setting: Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members. Patients, participants: Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013. Main outcome measure(s): We examined the proportion of opioid-tolerantonly ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥ 30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing. Results: We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opioid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation. Conclusions: These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

ObjectivesTo prospectively characterise: (1) postoperative opioid analgesic prescribing practices; (2) experience of patients undergoing elective ambulatory surgeries and (3) impact of patient risk for medication misuse on postoperative pain management.DesignLongitudinal survey of patients 7 days before and 7–14 days after surgery.SettingAcademic urban safety-net hospital.Participants181 participants recruited, 18 surgeons, follow-up data from 149 participants (82% retention); 54% women; mean age: 49 years.InterventionsNone.Primary and secondary outcome measuresTotal morphine equivalent dose (MED) prescribed and consumed, percentage of unused opioids.ResultsSurgeons postoperatively prescribed a mean of 242 total MED per patient, equivalent to 32 oxycodone (5 mg) pills. Participants used a mean of 116 MEDs (48%), equivalent to 18 oxycodone (5 mg) pills (~145 mg of oxycodone remaining per patient). A 10-year increase in patient age was associated with 12 (95% CI (−2.05 to –0.35)) total MED fewer prescribed opioids. Each one-point increase in the preoperative Graded Chronic Pain Scale was associated with an 18 (6.84 to 29.60) total MED increase in opioid consumption, and 5% (−0.09% to –0.005%) fewer unused opioids. Prior opioid prescription was associated with a 55 (5.38 to –104.82) total MED increase in opioid consumption, and 19% (−0.35% to –0.02%) fewer unused opioids. High-risk drug use was associated with 9% (−0.19% to 0.002%) fewer unused opioids. Pain severity in previous 3 months, high-risk alcohol, use and prior opioid prescription were not associated with postoperative prescribing practices.ConclusionsParticipants with a preoperative history of chronic pain, prior opioid prescription, and high-risk drug use were more likely to consume higher amounts of opioid medications postoperatively. Additionally, surgeons did not incorporate key patient-level factors (eg, substance use, preoperative pain) into opioid prescribing practices. Opportunities to improve postoperative opioid prescribing include system changes among surgical specialties, and patient education and monitoring.

Objective: A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics.Design: Retrospective cohort study.Setting: Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members.Patients, participants: Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013.Main outcome measure(s): We examined the proportion of opioid-tolerantonly ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing.Results: We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opioid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation.Conclusions: These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

OBJECTIVE: Experts cautioned that patients affected by the November 2010 withdrawal of the opioid analgesic propoxyphene might receive riskier prescriptions. To explore this, we compared drug receipt and outcomes among propoxyphene users before and after market withdrawal. STUDY DESIGN: Using OptumLabs data, we studied three populations: commercial, Medicare Advantage aged (age 65+) and Medicare Advantage disabled (age

Background Injection drug use–associated infective endocarditis (IDU-IE) is rising and valve surgery is frequently indicated. The effect of initiating public outcomes reporting for aortic valve surgery on rates of valve surgery and in-hospital mortality for endocarditis is not known. Methods For an interrupted time series analysis, we used data from the National Inpatient Sample, a representative sample of United States inpatient hospitalizations, from January 2010 to September 2015. We included individuals aged 18–65 with an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis of endocarditis. We defined IDU-IE using a validated combination of ICD-9 codes. We used segmented logistic regression to assess for changes in valve replacement and in-hospital mortality rates after the public reporting initiation in January 2013. Results We identified 7322 hospitalizations for IDU-IE and 23 997 for non–IDU-IE in the sample, representing 36 452 national IDU-IE admissions and 119 316 non-IDU admissions, respectively. Following the implementation of public reporting in 2013, relative to baseline trends, the odds of valve replacement decreased by 4.0% per quarter (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.93–0.99), with no difference by IDU status. The odds of an in-patient death decreased by 2.0% per quarter for both IDU-IE and non–IDU-IE cases following reporting (OR 0.98, 95% CI 0.97–0.99). Conclusions Initiating public reporting was associated with a significant decrease in valve surgery for all IE cases, regardless of IDU status, and a reduction in-hospital mortality for patients with IE. Patients with IE may have less access to surgery as a consequence of public reporting. To understand how reduced valve surgery impacts overall mortality, future studies should examine the postdischarge mortality rate.

Study objective Nonfatal opioid overdose represents an opportunity to engage young adults into using medication for opioid use disorder. We seek to describe characteristics of young adults who experience nonfatal overdose and estimate rates of and time to medication for opioid use disorder for young adults relative to those aged 26 to 45 years. Methods We conducted a cohort study using retrospective administrative data of 15,281 individuals aged 18 to 45 years who survived an opioid-related overdose in Massachusetts between 2012 and 2014, using deidentified, individual-level, linked data sets from Massachusetts government agencies. We described patient characteristics stratified by age (18 to 21, 22 to 25, and 26 to 45 years) and evaluated multivariable Cox proportional hazards models to compare rates of medication for opioid use disorder receipt, controlling for age, sex, history of mental health disorders, and addiction treatment. Results Among 4,268 young adults in the year after nonfatal overdose, 28% (n=336/1,209) of those aged 18 to 21, 36% (n=1,097/3,059) of those aged 22 to 25 years, and 36% (n=3,916/11,013) of those aged 26 to 45 years received medication for opioid use disorder. For individuals aged 18 to 21 and 22 to 25 years, median time to buprenorphine treatment was 4 months (interquartile range 1.7 to 1.8 months); to methadone treatment, 4 months (interquartile range 2.8 to 2.9 months); and to naltrexone treatment, 1 month (interquartile range 1 to 1 month). Individuals aged 18 to 21 years were less likely (adjusted hazard ratio 0.60 [95% confidence interval 0.45 to 0.70]) to receive methadone than those aged 22 to 25 and 26 to 45 years. Individuals aged 18 to 21 years and those aged 22 to 25 years were more likely to receive naltrexone (adjusted hazard ratio 1.65 [95% confidence interval 1.36 to 2.00] and 1.41 [95% confidence interval 1.23 to 1.61], respectively) than those aged 26 to 45 years. Conclusion One in 3 young adults received medication for opioid use disorder in the 12 months after surviving an overdose. Type of medication for opioid use disorder received appeared to be age associated. Future research should focus on how medication choice is made and how to optimize the emergency department for medication for opioid use disorder initiation after nonfatal overdose.

BACKGROUND: Patterns of inpatient opioid use and their associations with postdischarge opioid use are poorly understood. OBJECTIVE: To measure patterns in timing, duration, and setting of opioid administration in opioid-naive hospitalized patients and to examine associations with postdischarge use. DESIGN: Retrospective cohort study using electronic health record data from 2010 to 2014. SETTING: 12 community and academic hospitals in Pennsylvania. PATIENTS: 148 068 opioid-naive patients (191 249 admissions) with at least 1 outpatient encounter within 12 months before and after admission. MEASUREMENTS: Number of days and patterns of inpatient opioid use; any outpatient use (self-report and/or prescription orders) 90 and 365 days after discharge. RESULTS: Opioids were administered in 48% of admissions. Patients were given opioids for a mean of 67.9% (SD, 25.0%) of their stay. Location of administration of first opioid on admission, timing of last opioid before discharge, and receipt of nonopioid analgesics varied substantially. After adjustment for potential confounders, 5.9% of inpatients receiving opioids had outpatient use at 90 days compared with 3.0% of those without inpatient use (difference, 3.0 percentage points [95% CI, 2.8 to 3.2 percentage points]). Opioid use at 90 days was higher in inpatients receiving opioids less than 12 hours before discharge than in those with at least 24 opioid-free hours before discharge (7.5% vs. 3.9%; difference, 3.6 percentage points [CI, 3.3 to 3.9 percentage points]). Differences based on proportion of the stay with opioid use were modest (opioid use at 90 days was 6.4% and 5.4%, respectively, for patients with opioid use for ≥75% vs. ≤25% of their stay; difference, 1.0 percentage point [CI, 0.4 to 1.5 percentage points]). Associations were similar for opioid use 365 days after discharge. LIMITATION: Potential unmeasured confounders related to opioid use. CONCLUSION: This study found high rates of opioid administration to opioid-naive inpatients and associations between specific patterns of inpatient use and risk for long-term use after discharge. PRIMARY FUNDING SOURCE: UPMC Health System and University of Pittsburgh.

Summary Objective Tramadol has been widely used among patients with osteoarthritis (OA); however, there is paucity of information on its cardiovascular risk. We aimed to examine the association of tramadol with risk of myocardial infarction (MI) among patients with OA. Design Among OA patients aged 50–90 years without history of MI, cancer, or opioid use disorder in The Health Improvement Network database in the United Kingdom (2000–2016), three sequential propensity-score matched cohort studies were assembled, i.e., (1) patients who initiated tramadol or naproxen (negative comparator); (2) patients who initiated tramadol or diclofenac (positive comparator); and (3) patients who initiated tramadol or codeine (a commonly used weak opioid). The outcome was incident MI over six-months. Results Among tramadol and naproxen initiators (n = 33,024 in each cohort), 77 (4.8/1000 person-years) and 46 (2.8/1000 person-years) incident MI occurred, respectively. The rate difference (RD) and hazard ratios (HR) for incident MI with tramadol initiation were 1.9 (95% confidence interval [CI] 0.6 to 2.3)/1000 person-years and 1.68 (95% CI 1.16 to 2.41) relative to naproxen initiation, respectively. Among tramadol and diclofenac initiators (n = 18,662 in each cohort), 58 (6.4/1000 person-years) and 47 (5.1/1000 person-years) incident MIs occurred, respectively. The corresponding RD and HR for incident MI were 1.2 (95%CI -2.1 to 14.1)/1000 person-years and 1.24 (95%CI 0.84 to 1.82), respectively. Among tramadol and codeine initiators (n = 42,722 in each cohort), 127 (6.1/1000 person-years) and 103 (5.0/1000 person-years) incident MI occurred, respectively, and the corresponding RD and HR were 1.1 (95%CI:-0.3 to 2.5)/1000 person-years and 1.23 (95%CI:0.95 to 1.60), respectively. Conclusions In this population-based cohort of patients with OA, the six-month risk of MI among initiators of tramadol was higher than that of naproxen, but comparable to, if not lower than, those of diclofenac or codeine.