An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life.
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ABSTRACT:
SUBMITTER: Kimishima A
PROVIDER: S-EPMC6434689 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
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An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life.
Kimishima Atsushi A Wenthur Cody J CJ Zhou Bin B Janda Kim D KD
ACS chemical biology 20161129 1
Prescription opioids (POs) such as oxycodone and hydrocodone are highly effective medications for pain management, yet they also present a substantial risk for abuse and addiction. The consumption of POs has been escalating worldwide, resulting in tens of thousands of deaths due to overdose each year. Pharmacokinetic strategies based upon vaccination present an attractive avenue to suppress PO abuse. Herein, the preparation of two active PO vaccines is described that were found to elicit high-af ...[more]
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Project description:STUDY OBJECTIVE:The link between prescription opioid shopping and overdose events is poorly understood. We test the hypothesis that a history of prescription opioid shopping is associated with increased risk of overdose events. METHODS:This is a secondary analysis of a linked claims and controlled substance dispense database. We studied adult Medicaid beneficiaries in 2014 with prescription opioid use in the 6 months before an ambulatory care or emergency department visit with a pain-related diagnosis. The primary outcome was a nonfatal overdose event within 6 months of the cohort entry date. The exposure of interest (opioid shopping) was defined as having opioid prescriptions by different prescribers with greater than or equal to 1-day overlap and filled at 3 or more pharmacies in the 6 months before cohort entry. We used a propensity score to match shoppers with nonshoppers in a 1:1 ratio. We calculated the absolute difference in outcome rates between shoppers and nonshoppers. RESULTS:We studied 66,328 patients, including 2,571 opioid shoppers (3.9%). There were 290 patients (0.4%) in the overall cohort who experienced a nonfatal overdose. In unadjusted analyses, shoppers had higher event rates than nonshoppers (rate difference of 4.4 events per 1,000; 95% confidence interval 0.8 to 7.9). After propensity score matching, there were no outcome differences between shoppers and nonshoppers (rate difference of 0.4 events per 1,000; 95% confidence interval -4.7 to 5.5). These findings were robust to various definitions of opioid shoppers and look-back periods. CONCLUSION:Prescription opioid shopping is not independently associated with increased risk of overdose events.
| S-EPMC5960419 | biostudies-literature
Project description:IntroductionPrescription Drug Monitoring Program data can provide insights into a patient's likelihood of an opioid overdose, yet clinicians and public health officials lack indicators to identify individuals at highest risk accurately. A predictive model was developed and validated using Prescription Drug Monitoring Program prescription histories to identify those at risk for fatal overdose because of any opioid or illicit opioids.MethodsFrom December 2018 to July 2019, a retrospective cohort analysis was performed on Maryland residents aged 18-80 years with a filled opioid prescription (n=565,175) from January to June 2016. Fatal opioid overdoses were identified from the Office of the Chief Medical Examiner and were linked at the person-level with Prescription Drug Monitoring Program data. Split-half technique was used to develop and validate a multivariate logistic regression with a 6-month lookback period and assessed model calibration and discrimination.ResultsPredictors of any opioid-related fatal overdose included male sex, age 65-80 years, Medicaid, Medicare, 1 or more long-acting opioid fills, 1 or more buprenorphine fills, 2 to 3 and 4 or more short-acting schedule II opioid fills, opioid days' supply ≥91 days, average morphine milligram equivalent daily dose, 2 or more benzodiazepine fills, and 1 or more muscle relaxant fills. Model discrimination for the validation cohort was good (area under the curve: any, 0.81; illicit, 0.77).ConclusionsA model for predicting fatal opioid overdoses was developed using Prescription Drug Monitoring Program data. Given the recent national epidemic of deaths involving heroin and fentanyl, it is noteworthy that the model performed equally well in identifying those at risk for overdose deaths from both illicit and prescription opioids.
| S-EPMC7996003 | biostudies-literature
Project description:ImportanceSafe opioid prescribing practices are critical to mitigate the risk of prescription opioid overdose in adolescents and young adults. However, studies that examine opioid prescribing patterns associated with prescription opioid overdose have mostly focused on older adults. The generalizability of these studies to adolescents and young adults is unclear.ObjectiveTo identify opioid prescribing patterns associated with prescription opioid overdose in adolescents and young adults.Design, setting, and participantsThis retrospective cohort study assessed privately insured patients aged 12 to 21 years with opioid prescription claims in the IBM MarketScan Commercial Claims and Encounters database between July 1, 2009, and October 1, 2017, and no cancer diagnosis. Data analysis was performed from January 1 to April 30, 2019.Main outcomes and measuresThe outcome was a treated opioid overdose as indicated by diagnosis codes. On the basis of days supplied, opioid prescription claims were converted to person-days (the unit of analysis) on which opioid exposure would occur if patients took medications as prescribed. Logistic regression with clustered SEs at the patient level was used to model the occurrence of overdose on a person-day as a function of daily opioid dosage category (<30, 30-59, 60-89, 90-119, or ≥120 morphine milligram equivalents), concurrent benzodiazepine use, and extended-release or long-acting opioid use. Regressions controlled for demographic characteristics, year, opioid use within 180 days, and comorbidities (mental health disorder, substance use disorder, and other chronic condition).ResultsA total of 2 752 612 patients (mean [SD] age at cohort entry, 17.2 [2.5] years; 1 451 918 [52.8%] female) participated in the study. Patients had 4 686 355 opioid prescription claims, corresponding to 21 605 444 person-days. Overdose occurred on 255 person-days among 249 patients (0.01% of the sample). Each increase in daily opioid dosage category was associated with higher overdose risk (adjusted odds ratio [AOR], 1.18; 95% CI, 1.05-1.31). Compared with no use, both concurrent benzodiazepine use (AOR, 1.83; 95% CI, 1.24-2.71) and extended-release or long-acting opioid use (AOR, 2.01; 95% CI, 1.16-3.46) were associated with increased overdose risk.Conclusions and relevanceThe findings suggest that when prescribing opioids to adolescents and young adults, practitioners could potentially mitigate overdose risk by using the lowest effective daily dosage, avoiding concurrent opioid and benzodiazepine prescribing, and relying on short-acting opioids. Findings are broadly consistent with prior opioid safety studies focused on older adults.
| S-EPMC6990690 | biostudies-literature
Project description:IntroductionOpioid 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.MethodsThis 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.ResultsFollowing 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).ConclusionsEmergency 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.
| S-EPMC7311279 | biostudies-literature
Project description:US opioid overdose death rates have increased between 2000 and 2014. While, the increase in prescription opioid use has been linked to the increase in heroin use, there are reasons to view this relationship as a partial explanation for the recent increase in heroin-related harms. This study documents the differences in trends in prescription opioid overdose-related (POD) and heroin overdose-related (HOD) hospitalizations.Data come from the National Inpatient Sample (NIS) for the years 2000 through 2014. POD and HOD hospitalizations were abstracted from ICD-9 codes. Rates of POD and HOD by census region and census division were constructed along with separate rates for age and race. Regression analysis analyzing trends across region were estimated along with graphs for documenting differences in POD and HOD rates.POD hospitalization rates were highest in the South and lowest in the Northeast. HOD hospitalization rates were highest in the Northeast region and grew the fastest in the Midwest. There was statistically significant heterogeneity in HOD trends but not POD trends across the four regions between 2000 and 2014. Between 2012 and 2014 POD rates decreased in eight of the nine census divisions, with only New England showing an increase. HOD hospitalization rates increased in all nine census divisions between 2012 and 2014. Both POD and HOD rates show different demographic patterns across the nine census divisions.Comparing POD and HOD hospitalization trends reveals significant disparities in geographic as well as demographic distributions. These epidemics are evolving and the simple opioid-to-heroin transition story is both supported and challenged by this paper. The opioid pill, heroin and fentanyl crises are intertwined yet increasingly have drivers and outcomes that support examining them as distinct. Addressing these complex and interrelated epidemics will require innovative public health research and interventions which need to consider local and regional contexts.
| S-EPMC5722230 | biostudies-literature
Project description:ImportanceDeaths due to opioid overdose have tripled in the last decade. Efforts to curb this trend have focused on restricting the prescription opioid supply; however, the near-term effects of such efforts are unknown.ObjectiveTo project effects of interventions to lower prescription opioid misuse on opioid overdose deaths from 2016 to 2025.Design, setting, and participantsThis system dynamics (mathematical) model of the US opioid epidemic projected outcomes of simulated individuals who engage in nonmedical prescription or illicit opioid use from 2016 to 2025. The analysis was performed in 2018 by retrospectively calibrating the model from 2002 to 2015 data from the National Survey on Drug Use and Health and the Centers for Disease Control and Prevention.InterventionsComparison of interventions that would lower the incidence of prescription opioid misuse from 2016 to 2025 based on historical trends (a 7.5% reduction per year) and 50% faster than historical trends (an 11.3% reduction per year), vs a circumstance in which the incidence of misuse remained constant after 2015.Main outcomes and measuresOpioid overdose deaths from prescription and illicit opioids from 2016 to 2025 under each intervention.ResultsUnder the status quo, the annual number of opioid overdose deaths is projected to increase from 33 100 in 2015 to 81 700 (95% uncertainty interval [UI], 63 600-101 700) in 2025 (a 147% increase from 2015). From 2016 to 2025, 700 400 (95% UI, 590 200-817 100) individuals in the United States are projected to die from opioid overdose, with 80% of the deaths attributable to illicit opioids. The number of individuals using illicit opioids is projected to increase by 61%-from 0.93 million (95% UI, 0.83-1.03 million) in 2015 to 1.50 million (95% UI, 0.98-2.22 million) by 2025. Across all interventions tested, further lowering the incidence of prescription opioid misuse from 2015 levels is projected to decrease overdose deaths by only 3.0% to 5.3%.Conclusions and relevanceThis study's findings suggest that interventions targeting prescription opioid misuse such as prescription monitoring programs may have a modest effect, at best, on the number of opioid overdose deaths in the near future. Additional policy interventions are urgently needed to change the course of the epidemic.
| S-EPMC6415966 | biostudies-literature
Project description:Strategies are needed to identify at-risk patients for adverse events associated with prescription opioids. This study identified prescription opioid misuse in an integrated health system using electronic health record (EHR) data, and examined predictors of misuse and overdose. The sample included patients from an EHR-based registry of adults who used prescription opioids in 2011 in Kaiser Permanente Northern California, a large integrated health care system. We characterized time-at-risk for opioid misuse and overdose, and used Cox proportional hazard models to model predictors of these events from 2011 to 2014. Among 396,452 patients, 2.7% were identified with opioid misuse and 1044 had an overdose event. Older patients were less likely to meet misuse criteria or have an overdose. Whites were more likely to be identified with misuse, but not to have an overdose. Alcohol and drug disorders were related to higher risk of misuse and overdose, with the exception that marijuana disorder was not related to opioid misuse. Higher daily opioid dosages and benzodiazepine use increased the risk of both opioid misuse and overdose. We characterized several risk factors associated with misuse and overdose using EHR-based data, which can be leveraged relatively quickly to inform preventive strategies to address the opioid crisis.
| S-EPMC6034705 | biostudies-literature
Project description: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.
| S-EPMC6109008 | biostudies-other
Project description:OBJECTIVE:Although buprenorphine treatment reduces risk of overdose and death in opioid use disorder, most patients discontinue treatment within a few weeks or months. Adverse health outcomes following buprenorphine discontinuation were compared among patients who were successfully retained beyond 6 months of continuous treatment, a minimum treatment duration recently endorsed by the National Quality Forum. METHODS:A retrospective longitudinal cohort analysis was performed using the MarketScan multistate Medicaid claims database (2013-2017), covering 12 million beneficiaries annually. The sample included adults (18-64 years of age) who received buprenorphine continuously for ?180 days by cohorts retained for 6-9 months, 9-12 months, 12-15 months, and 15-18 months. For outcome assessment in the postdiscontinuation period, patients had to be continuously enrolled in Medicaid for 6 months after buprenorphine discontinuation. Primary adverse outcomes included all-cause emergency department visits, all-cause inpatient hospitalizations, opioid prescriptions, and drug overdose (opioid or non-opioid). RESULTS:Adverse events were common across all cohorts, and almost half of patients (42.1%-49.9%) were seen in the emergency department at least once. Compared with patients retained on buprenorphine for 6-9 months (N=4,126), those retained for 15-18 months (N=931) had significantly lower odds of emergency department visits (odds ratio=0.75, 95% CI=0.65-0.86), inpatient hospitalizations (odds ratio=0.79, 95% CI=0.64-0.99), and filling opioid prescriptions (odds ratio=0.67, 95% CI=0.56-0.80) in the 6 months following discontinuation. Approximately 5% of patients across all cohorts experienced one or more medically treated overdoses. CONCLUSIONS:Risk of acute care service use and overdose were high following buprenorphine discontinuation irrespective of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high.
| S-EPMC7002204 | biostudies-literature
Project description:Vaccines offer an option to treat heroin and prescription opioid abuse and prevent fatal overdoses. Opioid vaccines elicit antibodies that block opioid distribution to the brain and reduce opioid-induced behavioral effects and toxicity. The major limitation to the translation of addiction vaccines is that efficacy is observed only in subjects achieving optimal drug-specific serum antibody levels. This study tested whether efficacy of a vaccine against oxycodone is increased by immunomodulators targeting key cytokine signaling pathways involved in B and T cell lymphocyte activation. Blockage of IL-4 signaling increased vaccine efficacy in blocking oxycodone distribution to the brain and protection against opioid-induced behavior and toxicity in mice. This strategy generalized to a peptide-protein conjugate immunogen, and a tetanus-diphtheria-pertussis vaccine. These data demonstrate that cytokine-based immunomodulators increase efficacy of vaccines against small molecules, peptides and proteins, and identify IL-4 as a pharmacological target for improving efficacy of next-generation vaccines.
| S-EPMC5882912 | biostudies-literature