Prior Incarceration Is Associated with Poor Mental Health at Midlife: Findings from a National Longitudinal Cohort Study.

BACKGROUND: 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. OBJECTIVE: To evaluate prior incarceration's association with mental health at midlife. DESIGN: 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. MAIN MEASURES: 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. KEY RESULTS: 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. CONCLUSIONS: 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.

Association of Early Opioid Withdrawal Treatment Strategy and Patient-Directed Discharge Among Hospitalized Patients with Opioid Use Disorder.

BACKGROUND: Medical hospitalizations for people with opioid use disorder (OUD) frequently result in patient-directed discharges (PDD), often due to untreated pain and withdrawal. OBJECTIVE: To investigate the association between early opioid withdrawal management strategies and PDD. DESIGN: Retrospective cohort study using three datasets representing 362 US hospitals. PARTICIPANTS: Adult patients hospitalized between 2009 and 2015 with OUD (as identified using ICD-9-CM codes or inpatient buprenorphine administration) and no PDD on the day of admission. INTERVENTIONS: Opioid withdrawal management strategies were classified based on day-of-admission receipt of any of the following treatments: (1) medications for OUD (MOUD) including methadone or buprenorphine, (2) other opioid analgesics, (3) adjunctive symptomatic medications without opioids (e.g., clonidine), and (4) no withdrawal treatment. MAIN MEASURES: PDD was assessed as the main outcome and hospital length of stay as a secondary outcome. KEY RESULTS: Of 6,715,286 hospitalizations, 127,158 (1.9%) patients had OUD and no PDD on the day of admission, of whom 7166 (5.6%) had a later PDD and 91,051 (71.6%) patients received some early opioid withdrawal treatment (22.3% MOUD; 43.4% opioid analgesics; 5.9% adjunctive medications). Compared to no withdrawal treatment, MOUD was associated with a lower risk of PDD (adjusted odds ratio [aOR] = 0.73, 95%CI 0.68-0.8, p < .001), adjunctive treatment alone was associated with higher risk (aOR = 1.13, 95%CI: 1.01-1.26, p = .031), and treatment with opioid analgesics alone was associated with similar risk (aOR 0.95, 95%CI: 0.89-1.02, p = .148). Among those with PDD, both MOUD (adjusted incidence rate ratio [aIRR] = 1.24, 95%CI: 1.17-1.3, p < .001) and opioid analgesic treatments (aIRR = 1.39, 95%CI: 1.34-1.45, p < .001) were associated with longer hospital stays. CONCLUSIONS: MOUD was associated with decreased risk of PDD but was utilized in < 1 in 4 patients. Efforts are needed to ensure all patients with OUD have access to effective opioid withdrawal management to improve the likelihood they receive recommended hospital care.

Variation in Initiation, Engagement, and Retention on Medications for Opioid Use Disorder Based on Health Insurance Plan Design.

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 and information on insurance cost-sharing in a large national deidentified claims database. We examined 4 cost-sharing measures: (1) pharmacy deductible; (2) medical service deductible; (3) pharmacy medication copay; and (4) medical office copay. We measured MOUD (naltrexone, buprenorphine, or methadone) initiation (within 14 d of diagnosis), engagement (second receipt within 34 d of first), and 6-month retention (continuous receipt without 14-d 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 opioid use disorder, 1202 (11%) initiated MOUD, 742 (7%) engaged, and 253 (2%) were retained in MOUD at 6 months. A high ($1000+) medical deductible was associated with a lower odds of initiation compared with no deductible (odds ratio: 0.85, 95% confidence interval: 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. CONCLUSIONS: 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.

Patient Perspectives on Improving Patient-Provider Relationships and Provider Communication During Opioid Tapering.

BACKGROUND: Efforts to reduce opioid overdose fatalities have resulted in tapering (i.e., reducing or discontinuing) opioid prescriptions despite a limited understanding of patients' experiences. OBJECTIVE: To explore patients' perspectives on opioid taper experiences to ultimately improve taper processes and outcomes. DESIGN: Qualitative study. PARTICIPANTS: Patients on long-term opioid therapy for chronic pain who had undergone a reduction of opioid daily prescribed dosage of ≥50% in the past 2 years in two distinct medical systems and regions. APPROACH: From 2019 to 2020, we conducted semi-structured interviews that were audio-recorded, transcribed, systematically coded, and analyzed to summarize the content and identify key themes regarding taper experiences overall and with particular attention to patient-provider relationships and provider communication during tapers. KEY RESULTS: Participants (n=41) had lived with chronic pain for an average of 17.4 years (range, 3-36 years) and described generally adverse experiences with opioid tapers, the initiation of which was not always adequately justified or explained to them. Consequences of tapers ranged from minor to substantial and included withdrawal, mobility issues, emotional distress, exacerbated mental health symptoms, and feelings of social stigmatization for which adequate supports were typically unavailable. Narratives highlighted the consequential role of patient-provider relationships throughout taper experiences, with most participants describing significant interpersonal challenges including poor provider communication and limited patient engagement in decision making. A few participants identified qualities of providers, relationships, and communication that fostered more positive taper experiences and outcomes. CONCLUSIONS: From patients' perspectives, opioid tapers can produce significant physical, emotional, and social consequences, sometimes reducing trust and engagement in healthcare. Patient-provider relationships and communication influence patients' perceptions of the quality and outcomes of opioid tapers. To improve patients' experiences of opioid tapers, tapering plans should be based on individualized risk-benefit assessments and involve patient-centered approaches and improved provider communication.

Do Urine Drug Tests Reveal Substance Misuse Among Patients Prescribed Opioids for Chronic Pain?

BACKGROUND: 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. OBJECTIVE: Identify the prevalence of UDT results that may identify substance misuse, including diversion, among patients prescribed opioids for chronic pain. DESIGN: Retrospective cohort study. SUBJECTS: 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. MAIN MEASURES: Experts adjudicated the clinical concern that UDT results suggest substance misuse or diversion as not concerning, uncertain, or concerning. KEY RESULTS: 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. CONCLUSIONS: 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.

Effect of police action on low-barrier substance use disorder service utilization.

BACKGROUND: Police action can increase risky substance use patterns by people who use drugs (PWUD), but it is not known how increased police presence affects utilization of low-barrier substance use disorder bridge clinics. Increased police presence may increase or decrease treatment-seeking behavior. We examined the association between Operation Clean Sweep (OCS), a 2-week police action in Boston, MA, and visit volume in BMC's low-barrier buprenorphine bridge clinic. METHODS: In this retrospective cohort, we used segmented regression to investigate whether the increased police presence during OCS was associated with changes in bridge clinic visits. We used General Internal Medicine (GIM) clinic visit volume as a negative control. We examined visits during the 6 weeks prior, 2 weeks during, and 4 weeks after OCS (June 18-September 11, 2019). RESULTS: Bridge clinic visits were 2.8 per provider session before, 2.0 during, and 3.0 after OCS. The mean number of GIM clinic visits per provider session before OCS was 7.0, 6.8 during, and 7.0 after OCS. In adjusted segmented regression models for bridge clinic visits per provider session, there was a nonsignificant level increase (0.643 P = 0.171) and significant decrease in slope (0.100, P = 0.045) during OCS. After OCS completed, there was a significant level increase (1.442, P = 0.003) and slope increase in visits per provider session (0.141, P = 0.007). There was no significant change in GIM clinic volume during the study period. CONCLUSIONS: The increased policing during OCS was associated with a significant decrease in bridge clinic visits. Following the completion of OCS, there was a significant increase in clinic visits, suggesting pent-up demand for medications for opioid use disorder, a life-saving treatment.

Against Medical Advice Discharges in Injection and Non-injection Drug Use-associated Infective Endocarditis: A Nationwide Cohort Study.

BACKGROUND: Among 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. METHODS: We 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. RESULTS: We 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). CONCLUSIONS: AMA 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.

Epidemiology, Outcomes, and Trends of Patients With Sepsis and Opioid-Related Hospitalizations in U.S. Hospitals.

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.

Disparities in Opioid Overdose Death Trends by Race/Ethnicity, 2018-2019, From the HEALing Communities Study.

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).

HIV testing among people with and without substance use disorder in emergency departments: A nationwide cohort study.

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.

Relative Cost Differences of Initial Treatment Strategies for Newly Diagnosed Opioid Use Disorder: A Cohort Study.

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.

Characteristics and Receipt of Medication Treatment Among Young Adults Who Experience a Nonfatal Opioid-Related Overdose.

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.

Changes to dietary and health outcomes following implementation of the 2012 updated US Department of Agriculture school nutrition standards: analysis using National Health and Nutrition Examination Survey, 2005-2016.

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 (ß = 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.

Assessment of prior opioid tolerance among new users of fentanyl transdermal system in FDA's Sentinel System.

PURPOSE: Fentanyl transdermal system (FTS) is intended only for patients with prior opioid tolerance. The purpose of this study is to identify the proportion of new FTS users who had evidence of prior opioid tolerance, by dosage strength, in FDA's Sentinel System. METHODS: We identified new FTS episodes (183-day washout) from 2009 through 2013. Members were <65 years and enrolled in medical and pharmacy coverage for 183 days prior to initial FTS dispensing (index). We assessed the proportion of users with prior tolerance stratified by dosage strength of FTS using four definitions of opioid tolerance: ≥30-mg oxycodone equivalents/day in each of 7 consecutive days immediately prior to index; ≥30-mg oxycodone equivalents/day for any 7 days in the 30 days prior to index (secondary); any dose in each of 7 days in the 7 consecutive days immediately prior to index (tertiary); and any dose for any 7 days in the 30 days prior to index (quaternary). RESULTS: Of 44 450 episodes of 25 mcg/hr FTS, 37% met the primary definition, and 77% met the quaternary definition. Of 3507 episodes of 100 mcg/hr FTS, 57% and 74% met the primary and quaternary definitions, respectively. Those aged 25 to 34 years had the highest proportion of episodes with prior tolerance; those aged 55 to 64 accounted for more of the episodes overall. CONCLUSIONS: In Sentinel, many new users of FTS did not have evidence of prior opioid tolerance by the primary definition, ie, the product label definition, which is the minimum standard for the lowest FTS dose (12 mcg/hr), especially at the highest strength (100 mcg/hr). Validation of this metric is warranted, but our findings suggest the need for further prescriber education regarding appropriate prescribing of FTS.

Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study.

Background: Opioid overdose survivors have an increased risk for death. Whether use of medications for opioid use disorder (MOUD) after overdose is associated with mortality is not known. Objective: To identify MOUD use after opioid overdose and its association with all-cause and opioid-related mortality. Design: Retrospective cohort study. Setting: 7 individually linked data sets from Massachusetts government agencies. Participants: 17 568 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014. Measurements: Three types of MOUD were examined: methadone maintenance treatment (MMT), buprenorphine, and naltrexone. Exposure to MOUD was identified at monthly intervals, and persons were considered exposed through the month after last receipt. A multivariable Cox proportional hazards model was used to examine MOUD as a monthly time-varying exposure variable to predict time to all-cause and opioid-related mortality. Results: In the 12 months after a nonfatal overdose, 2040 persons (11%) enrolled in MMT for a median of 5 months (interquartile range, 2 to 9 months), 3022 persons (17%) received buprenorphine for a median of 4 months (interquartile range, 2 to 8 months), and 1099 persons (6%) received naltrexone for a median of 1 month (interquartile range, 1 to 2 months). Among the entire cohort, all-cause mortality was 4.7 deaths (95% CI, 4.4 to 5.0 deaths) per 100 person-years and opioid-related mortality was 2.1 deaths (CI, 1.9 to 2.4 deaths) per 100 person-years. Compared with no MOUD, MMT was associated with decreased all-cause mortality (adjusted hazard ratio [AHR], 0.47 [CI, 0.32 to 0.71]) and opioid-related mortality (AHR, 0.41 [CI, 0.24 to 0.70]). Buprenorphine was associated with decreased all-cause mortality (AHR, 0.63 [CI, 0.46 to 0.87]) and opioid-related mortality (AHR, 0.62 [CI, 0.41 to 0.92]). No associations between naltrexone and all-cause mortality (AHR, 1.44 [CI, 0.84 to 2.46]) or opioid-related mortality (AHR, 1.42 [CI, 0.73 to 2.79]) were identified. Limitation: Few events among naltrexone recipients preclude confident conclusions. Conclusion: A minority of opioid overdose survivors received MOUD. Buprenorphine and MMT were associated with reduced all-cause and opioid-related mortality. Primary Funding Source: National Center for Advancing Translational Sciences of the National Institutes of Health.

Association of Tramadol With All-Cause Mortality Among Patients With Osteoarthritis.

Importance: An American Academy of Orthopaedic Surgeons guideline recommends tramadol for patients with knee osteoarthritis, and an American College of Rheumatology guideline conditionally recommends tramadol as first-line therapy for patients with knee osteoarthritis, along with nonsteroidal anti-inflammatory drugs. Objective: To examine the association of tramadol prescription with all-cause mortality among patients with osteoarthritis. Design, Setting, and Participants: Sequential, propensity score-matched cohort study at a general practice in the United Kingdom. Individuals aged at least 50 years with a diagnosis of osteoarthritis in the Health Improvement Network database from January 2000 to December 2015, with follow-up to December 2016. Exposures: Initial prescription of tramadol (n = 44 451), naproxen (n = 12 397), diclofenac (n = 6512), celecoxib (n = 5674), etoricoxib (n = 2946), or codeine (n = 16 922). Main Outcomes and Measures: All-cause mortality within 1 year after initial tramadol prescription, compared with 5 other pain relief medications. Results: After propensity score matching, 88 902 patients were included (mean [SD] age, 70.1 [9.5] years; 61.2% were women). During the 1-year follow-up, 278 deaths (23.5/1000 person-years) occurred in the tramadol cohort and 164 (13.8/1000 person-years) occurred in the naproxen cohort (rate difference, 9.7 deaths/1000 person-years [95% CI, 6.3-13.2]; hazard ratio [HR], 1.71 [95% CI, 1.41-2.07]), and mortality was higher for tramadol compared with diclofenac (36.2/1000 vs 19.2/1000 person-years; HR, 1.88 [95% CI, 1.51-2.35]). Tramadol was also associated with a higher all-cause mortality rate compared with celecoxib (31.2/1000 vs 18.4/1000 person-years; HR, 1.70 [95% CI, 1.33-2.17]) and etoricoxib (25.7/1000 vs 12.8/1000 person-years; HR, 2.04 [95% CI, 1.37-3.03]). No statistically significant difference in all-cause mortality was observed between tramadol and codeine (32.2/1000 vs 34.6/1000 person-years; HR, 0.94 [95% CI, 0.83-1.05]). Conclusions and Relevance: Among patients aged 50 years and older with osteoarthritis, initial prescription of tramadol was associated with a significantly higher rate of mortality over 1 year of follow-up compared with commonly prescribed nonsteroidal anti-inflammatory drugs, but not compared with codeine. However, these findings may be susceptible to confounding by indication, and further research is needed to determine if this association is causal.

Potentially Inappropriate Opioid Prescribing, Overdose, and Mortality in Massachusetts, 2011-2015.

BACKGROUND: Potentially inappropriate prescribing (PIP) may contribute to opioid overdose. OBJECTIVE: To examine the association between PIP and adverse events. DESIGN: Cohort study. PARTICIPANTS: Three million seventy-eight thousand thirty-four individuals age ≥ 18, without disseminated cancer, who received prescription opioids between 2011 and 2015. MAIN MEASURES: We defined PIP as (a) morphine equivalent dose ≥ 100 mg/day in ≥ 3 months; (b) overlapping opioid and benzodiazepine prescriptions in ≥ 3 months; (c) ≥ 4 opioid prescribers in any quarter; (d) ≥ 4 opioid-dispensing pharmacies in any quarter; (e) cash purchase of prescription opioids on ≥ 3 occasions; and (f) receipt of opioids in 3 consecutive months without a documented pain diagnosis. We used Cox proportional hazards models to identify PIP practices associated with non-fatal opioid overdose, fatal opioid overdose, and all-cause mortality, controlling for covariates. KEY RESULTS: All six types of PIP were associated with higher adjusted hazard for all-cause mortality, four of six with non-fatal overdose, and five of six with fatal overdose. Lacking a documented pain diagnosis was associated with non-fatal overdose (adjusted hazard ratio [AHR] 2.21, 95% confidence interval [CI] 2.02-2.41), as was high-dose opioids (AHR 1.68, 95% CI 1.59-1.76). Co-prescription of benzodiazepines was associated with fatal overdose (AHR 4.23, 95% CI 3.85-4.65). High-dose opioids were associated with all-cause mortality (AHR 2.18, 95% CI 2.14-2.23), as was lacking a documented pain diagnosis (AHR 2.05, 95% CI 2.01-2.09). Compared to those who received opioids without PIP, the hazard for fatal opioid overdose with one, two, three, and ≥ four PIP subtypes were 4.24, 7.05, 10.28, and 12.99 (test of linear trend, p < 0.001). CONCLUSIONS: PIP was associated with higher hazard for all-cause mortality, fatal overdose, and non-fatal overdose. Our study implies the possibility of creating a risk score incorporating multiple PIP subtypes, which could be displayed to prescribers in real time.

Estimated Prevalence of Opioid Use Disorder in Massachusetts, 2011-2015: A Capture-Recapture Analysis.

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.