Mortality Following Nonfatal Opioid and Sedative/Hypnotic Drug Overdose.
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ABSTRACT: Introduction
Opioid and sedative/hypnotic drug overdoses are major causes of morbidity in the U.S. This study compares 12-month incidence of fatal unintentional drug overdose, suicide, and other mortality among emergency department patients presenting with nonfatal opioid or sedative/hypnotic overdose.Methods
This is a retrospective cohort study using statewide, longitudinally linked emergency department patient record and mortality data from California. Participants comprised all residents presenting to a licensed emergency department at least once in 2009-2011 with nonfatal unintentional opioid overdose, sedative/hypnotic overdose, or neither (a 5% random sample). Participants were followed for 1 year after index emergency department presentation to assess death from unintentional overdose, suicide, or other causes, ascertained using ICD-10 codes. Absolute death rates per 100,000 person years and standardized mortality ratios relative to the general population were calculated. Data were analyzed February-August 2019.Results
Following the index emergency department visit, unintentional overdose death rates per 100,000 person years were 1,863 following opioid overdose, 342 following sedative/hypnotic overdose, and 31 for reference patients without an index overdose (respective standardized mortality ratios of 106.1, 95% CI=95.2, 116.9; 24.5, 95% CI=21.3, 27.6; and 2.6, 95% CI=2.2, 3.0). Suicide mortality rates per 100,000 were 319, 174, and 32 following opioid overdose, sedative/hypnotic overdose, and reference visits, respectively. Natural causes mortality rates per 100,000 were 8,058 (opioid overdose patients), 17,301 (sedative/hypnotic overdose patients), and 3,097 (reference patients).Conclusions
Emergency department patients with nonfatal opioid or sedative/hypnotic drug overdose have exceptionally high risks of death from unintentional overdose, suicide, and other causes. Emergency department-based interventions offer potential for reducing these patients' overdose and other mortality risks.
SUBMITTER: Goldman-Mellor S
PROVIDER: S-EPMC7311279 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLittle is known about risk factors for repeated opioid overdose and fatal opioid overdose in the first year following nonfatal opioid overdose.MethodsWe identified a national retrospective longitudinal cohort of patients aged 18-64 years in the Medicaid program who received a clinical diagnosis of nonfatal opioid overdose. Repeated overdoses and fatal opioid overdoses were measured with the Medicaid record and the National Death Index. Rates of repeat overdose per 1000 person-years and fatal overdose per 100,000 person-years were determined. Hazard ratios of repeated opioid overdose and fatal opioid overdose were estimated by Cox proportional hazards.ResultsNearly two-thirds (64.8%) of the patients with nonfatal overdoses (total n = 75,556) had filled opioid prescriptions in the 180 days before initial overdose. During the 12 months after nonfatal overdose, the rate of repeat overdose was 295.0 per 1000 person-years and that of fatal opioid overdose was 1154 per 100,000 person-years. After controlling for age, sex, race/ethnicity, and region, the hazard of fatal opioid overdose was increased for patients who had filled a benzodiazepine prescription in the 180 days prior to their initial overdose (HR = 1.71, 95%CI: 1.46-1.99), whose initial overdose involved heroin (HR = 1.57, 95%CI:1.30-1.89), or who required mechanical ventilation at the initial overdose (HR = 1.86, 95%CI = 1.50-2.31).ConclusionsAdults treated for opioid overdose frequently have repeated opioid overdoses in the following year. They are also at high risk of fatal opioid overdose throughout this period, which underscores the importance of efforts to engage and maintain patients in evidence-based opioid treatments following nonfatal overdose.
| S-EPMC10398609 | biostudies-literature
Project description:ImportanceA recent increase in patients presenting with nonfatal opioid overdoses has focused clinical attention on characterizing their risks of premature mortality.ObjectiveTo describe all-cause mortality rates, selected cause-specific mortality rates, and standardized mortality rate ratios (SMRs) of adults during their first year after nonfatal opioid overdose.Design, setting, and participantsThis US national longitudinal study assesses a cohort of patients aged 18 to 64 years who were Medicaid beneficiaries and experienced nonfatal opioid overdoses. The Medicaid data set included the years 2001 through 2007. Death record information was obtained from the National Death Index. Data analysis occurred from October 2017 to January 2018.Main outcomes and measuresCrude mortality rates per 100 000 person-years were determined in the first year after nonfatal opioid overdose. Standardized mortality rate ratios (SMR) were estimated for all-cause and selected cause-specific mortality standardized to the general population with respect to age, sex, and race/ethnicity.ResultsThe primary cohort included 76 325 adults and 66 736 person-years of follow-up. During the first year after nonfatal opioid overdose, there were 5194 deaths, the crude death rate was 778.3 per 10 000 person-years, and the all-cause SMR was 24.2 (95% CI, 23.6-24.9). The most common immediate causes of death were substance use-associated diseases (26.2%), diseases of the circulatory system (13.2%), and cancer (10.3%). For every cause examined, SMRs were significantly elevated, especially with respect to drug use-associated diseases (SMR, 132.1; 95% CI, 125.6-140.0), HIV (SMR, 45.9; 95% CI, 39.5-53.0), chronic respiratory diseases (SMR, 41.1; 95% CI, 36.0-46.8), viral hepatitis (SMR, 30.6; 95% CI, 22.9-40.2), and suicide (SMR, 25.9; 95% CI, 22.6-29.6), particularly including suicide among females (SMR, 47.9; 95% CI, 39.8-52.3).Conclusions and relevanceIn a US national cohort of adults who had experienced a nonfatal opioid overdose, a marked excess of deaths was attributable to a wide range of substance use-associated, mental health, and medical conditions, underscoring the importance of closely coordinating the substance use, mental health, and medical care of this patient population.
| S-EPMC6143082 | biostudies-literature
Project description:BackgroundOpioid 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.ObjectiveTo identify MOUD use after opioid overdose and its association with all-cause and opioid-related mortality.DesignRetrospective cohort study.Setting7 individually linked data sets from Massachusetts government agencies.Participants17 568 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014.MeasurementsThree 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.ResultsIn 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.LimitationFew events among naltrexone recipients preclude confident conclusions.ConclusionA minority of opioid overdose survivors received MOUD. Buprenorphine and MMT were associated with reduced all-cause and opioid-related mortality.Primary funding sourceNational Center for Advancing Translational Sciences of the National Institutes of Health.
| S-EPMC6387681 | biostudies-literature
Project description:Importance:Timely initiation and referral to treatment for patients with opioid use disorder seen in the emergency department is associated with reduced mortality. It is not known how often commercially insured adults obtain follow-up treatment after nonfatal opioid overdose. Objective:To investigate the incidence of follow-up treatment following emergency department discharge after nonfatal opioid overdose and patient characteristics associated with receipt of follow-up treatment. Design, Setting, and Participants:A retrospective cohort study was conducted using an administrative claims database for a large US commercial insurer, from October 1, 2011, to September 30, 2016. Data analysis was performed from May 1, 2019, to September 26, 2019. Adult patients discharged from the emergency department after an index opioid overdose (no overdose in the preceding 90 days) were included. Patients with cancer and without continuous insurance enrollment were excluded. Main Outcomes and Measures:The primary outcome was follow-up treatment in the 90 days following overdose, defined as a combined outcome of claims for treatment encounters or medications for opioid use disorder (buprenorphine and naltrexone). Analysis was stratified by whether patients received treatment for opioid use disorder in the 90 days before the overdose. Logistic regression models were used to identify patient characteristics associated with receipt of follow-up treatment. Marginal effects were used to report the average adjusted probability and absolute risk differences (ARDs) in follow-up for different patient characteristics. Results:A total of 6451 patients were identified with nonfatal opioid overdose; the mean (SD) age was 45.0 (19.3) years, 3267 were women (50.6%), and 4676 patients (72.5%) reported their race as non-Hispanic white. A total of 1069 patients (16.6%; 95% CI, 15.7%-17.5%) obtained follow-up treatment within 90 days after the overdose. In adjusted analysis of patients who did not receive treatment before the overdose, black patients were half as likely to obtain follow-up compared with non-Hispanic white patients (ARD, -5.9%; 95% CI, -8.6% to -3.6%). Women (ARD, -1.7%; 95% CI, -3.3% to -0.5%) and Hispanic patients (ARD, -3.5%; 95% CI, -6.1% to -0.9%) were also less likely to obtain follow-up. For each additional year of age, patients were 0.2% less likely to obtain follow-up (95% CI, -0.3% to -0.1%). Conclusions and Relevance:Efforts to improve the low rate of timely follow-up treatment following opioid overdose may seek to address sex, race/ethnicity, and age disparities.
| S-EPMC7254182 | biostudies-literature
Project description:ObjectivesOpioid-related overdose is a public health emergency in the United States. Meanwhile, high-deductible health plans (HDHPs) have become more prevalent in the United States over the last 2 decades, raising concern about their potential for discouraging high-need populations, like those with opioid use disorder (OUD), from engaging in care that may mitigate the probability of overdose. This study assesses the impact of an employer offering an HDHP on nonfatal opioid overdose among commercially insured individuals with OUD in the United States.Research designWe used deidentified insurance claims data from 2007 to 2017 with 97,788 person-years. We used an intent-to-treat, difference-in-differences regression framework to estimate the change in the probability of a nonfatal opioid overdose among enrollees with OUD whose employers began offering an HDHP insurance option during the study period compared with the change among those whose employer never offered an HDHP. We also used an event-study model to account for dynamic time-varying treatment effects.ResultsAcross both comparison and treatment groups, 2% of the sample experienced a nonfatal opioid overdose during the study period. Our primary model and robustness checks revealed no impact of HDHP offer on the probability of a nonfatal overdose.ConclusionsOur study suggests that HDHP offer was not associated with an observed increase in the probability of nonfatal opioid overdose among commercially insured person-years with OUD. However, given the strong evidence that medications for OUD (MOUD) can reduce the risk of overdose, research should explore which facets of insurance design may impact MOUD use.
| S-EPMC10527154 | biostudies-literature
Project description:BackgroundSurvivors of opioid overdose have substantially increased mortality risk, although this risk is not evenly distributed across individuals. No study has focused on predicting an individual's risk of death after a nonfatal opioid overdose.ObjectiveTo predict risk of death after a nonfatal opioid overdose.Design and participantsThis retrospective cohort study included 9686 Pennsylvania Medicaid beneficiaries with an emergency department or inpatient claim for nonfatal opioid overdose in 2014-2016. The index date was the first overdose claim during this period.Exposures, main outcome, and measuresPredictor candidates were measured in the 180 days before the index overdose. Primary outcome was 180-day all-cause mortality. Using a gradient boosting machine model, we classified beneficiaries into six subgroups according to their risk of mortality (< 25th percentile of the risk score, 25th to < 50th, 50th to < 75th, 75th to < 90th, 90th to < 98th, ≥ 98th). We then measured receipt of medication for opioid use disorder (OUD), risk mitigation interventions (e.g., prescriptions for naloxone), and prescription opioids filled in the 180 days after the index overdose, by risk subgroup.Key resultsOf eligible beneficiaries, 347 (3.6%) died within 180 days after the index overdose. The C-statistic of the mortality prediction model was 0.71. In the highest risk subgroup, the observed 180-day mortality rate was 20.3%, while in the lowest risk subgroup, it was 1.5%. Medication for OUD and risk mitigation interventions after overdose were more commonly seen in lower risk groups, while opioid prescriptions were more likely to be used in higher risk groups (both p trends < .001).ConclusionsA risk prediction model performed well for classifying mortality risk after a nonfatal opioid overdose. This prediction score can identify high-risk subgroups to target interventions to improve outcomes among overdose survivors.
| S-EPMC8041978 | biostudies-literature
Project description:IntroductionAmong individuals who are released from prison, opioid overdose is a leading cause of death with a risk more than ten-fold the general population. Although the epidemiology of opioid-related fatalities has been described, few studies have characterized both fatal and nonfatal opioid-related poisonings. The objective of this study was to estimate risk of fatal and nonfatal opioid overdose among adults released from prison.MethodsThe study estimated fatal and nonfatal opioid overdose rates using linked corrections, Medicaid, hospital discharge, and vital statistics from the state of Oregon from 2014 to 2018. Multivariable proportional hazards models identified demographic and prison-related factors associated with overdose.ResultsBetween 2014 and 2017, 18,258 individuals were released from prison. A majority of individuals were male (87 %) and ages 26 to 64 (83 %). Two-thirds had a documented substance use disorder treatment need and 20 % demonstrated mental health treatment need. Following prison release, 579 opioid overdose events occurred; 65 (11 %) were fatal. The rate of opioid overdose was 1085.7 per 100,000 person-years (PY). Rates were highest in the first two weeks (2286.7 per 100,000 PY), among women (1582.9 per 100,000 PY), and those with mental health (1624.3 per 100,000 PY) or substance use disorder treatment needs (1382.6 per 100,100 PY). Only mental health (adjusted hazard ratio [aHR] 1.54, 95 % CI 1.24 to 1.90) and substance use need (aHR 2.59; 95 % CI 2.01 to 3.34) remained significant in multivariable models.ConclusionsThe rate of opioid overdose is markedly elevated after prison release, particularly in the first two weeks. In women, the higher rate of opioid overdose is mediated by a greater mental health burden.
| S-EPMC10795482 | biostudies-literature
Project description:2,2,2-Trichloroethanol (TCE) is the active form of the sedative hypnotic drug chloral hydrate, one of the oldest sleep medications in the market. Understanding of TCE's action mechanisms to its many targets, particularly within the ion channel family, could benefit from the state-of-the-art computational molecular studies. In this direction, we employed de novo modeling aided by the force field toolkit to develop CHARMM36-compatible TCE parameters. The classical potential energy function was calibrated targeting molecular conformations, local interactions with water molecules, and liquid bulk properties. Reference data comes from both tabulated thermodynamic properties and ab initio calculations at the MP2 level. TCE solvation free energy calculations in water and oil reproduce a lipophilic, yet nonhydrophobic, behavior. Indeed, the potential mean force profile for TCE partition through the phospholipid bilayer reveals the sedative's preference for the interfacial region. The calculated partition coefficient also matches experimental measures. Further validation of the proposed parameters is supported by the model's ability to recapitulate quenching experiments demonstrating TCE binding to bovine serum albumin.
| S-EPMC6288786 | biostudies-literature
Project description:ImportanceOverdoses continue to increase in the US, but the contribution of methamphetamine use is understudied in rural communities.ObjectiveTo estimate the prevalence of methamphetamine use and its correlates among people who use drugs (PWUD) in rural US communities and to determine whether methamphetamine use is associated with increased nonfatal overdoses.Design, setting, and participantsFrom January 2018 through March 2020, the National Rural Opioid Initiative conducted cross-sectional surveys of PWUD in rural communities in 10 states (Illinois, Kentucky, New Hampshire, Massachusetts, North Carolina, Ohio, Oregon, Vermont, West Virginia, and Wisconsin). Participants included rural PWUD who reported any past-30-day injection drug use or noninjection opioid use to get high. A modified chain-referral sampling strategy identified seeds who referred others using drugs. Data analysis was performed from May 2021 to January 2022.ExposuresUse of methamphetamine alone, opioids alone, or both.Main outcomes and measuresUnweighted and weighted prevalence of methamphetamine use, any past-180-day nonfatal overdose, and number of lifetime nonfatal overdoses.ResultsAmong the 3048 participants, 1737 (57%) were male, 2576 (85%) were White, and 225 (7.4%) were American Indian; the mean (SD) age was 36 (10) years. Most participants (1878 of 2970 participants with any opioid or methamphetamine use [63%]) reported co-use of methamphetamine and opioids, followed by opioids alone (702 participants [24%]), and methamphetamine alone (390 participants [13%]). The estimated unweighted prevalence of methamphetamine use was 80% (95% CI, 64%-90%), and the estimated weighted prevalence was 79% (95% CI, 57%-91%). Nonfatal overdose was greatest in people using both methamphetamine and opioids (395 of 2854 participants with nonmissing overdose data [22%]) vs opioids alone (99 participants [14%]) or methamphetamine alone (23 participants [6%]). Co-use of methamphetamine and opioids was associated with greater nonfatal overdose compared with opioid use alone (adjusted odds ratio, 1.45; 95% CI, 1.08-1.94; P = .01) and methamphetamine use alone (adjusted odds ratio, 3.26; 95% CI, 2.06-5.14; P < .001). Those with co-use had a mean (SD) of 2.4 (4.2) (median [IQR], 1 [0-3]) lifetime overdoses compared with 1.7 (3.5) (median [IQR], 0 [0-2]) among those using opioids alone (adjusted rate ratio, 1.20; 95% CI, 1.01-1.43; P = .04), and 1.1 (2.9) (median [IQR], 0 [0-1]) among those using methamphetamine alone (adjusted rate ratio, 1.81; 95% CI, 1.45-2.27; P < .001). Participants with co-use most often reported having tried and failed to access substance use treatment: 827 participants (44%) for both, 117 participants (30%) for methamphetamine alone, and 252 participants (36%) for opioids alone (χ22 = 33.8; P < .001). Only 66 participants (17%) using methamphetamine alone had naloxone.Conclusions and relevanceThese findings suggest that harm reduction and substance use disorder treatment interventions must address both methamphetamine and opioids to decrease overdose in rural communities.
| S-EPMC9379740 | biostudies-literature
Project description:BackgroundBenzodiazepines and sedative-hypnotic drugs (BZD/SHDs), such as zopiclone and the antidepressant trazodone, pose risks such as falls, fractures, and confusion, especially for older adults. Use of these drugs in the acute care setting is poorly understood.ObjectivesTo determine the point prevalence and characteristics of use of BZD/SHDs in hospitals in Nova Scotia, Canada.MethodsA point prevalence survey was conducted for adults admitted to all hospitals with at least 30 acute care beds between May and August 2016. Drugs administered intravenously, patients in long-term care, and patients receiving mental health services, addiction treatment, or critical care were excluded. The proportion of included patients who had received a BZD/SHD within the 24 h before the start of the survey was determined. A descriptive statistical analysis was performed.ResultsOverall BZD/SHD prevalence was 34.6% (487/1409) across the 16 eligible hospitals. The average age was 70.3 years, and 150 (30.8%) of the patients were 80 years or older. Among the 585 prescriptions for these patients, commonly used drugs were zopiclone (32.0%), lorazepam (21.9%), and trazodone (21.9%). The most common indications for use were bedtime/daytime sedation (60.0%) and anxiety (12.5%). More than half of the prescriptions (55.7%) had been initiated at home, 37.6% were started in hospital, and the place of initiation was unknown for 6.7%. Benzodiazepines were prescribed more frequently to patients under 65 years than those 80 years or older (41.3% versus 22.2%, p < 0.001) whereas trazodone was more frequently prescribed to the older of these 2 age groups (52.7% versus 14.3%, p < 0.001).ConclusionsBZD/SHDs were frequently used by hospitalized adult patients in Nova Scotia. Trazodone appears to have been substituted for benzodiazepines in the oldest age group. Pharmacists should direct their efforts toward preventing inappropriate initiation of BZD/SHDs in hospital, particularly for elderly patients.
| S-EPMC7308153 | biostudies-literature