Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose.
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ABSTRACT:
SUBMITTER: Laudenbach M
PROVIDER: S-EPMC5882912 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We report our results of RNA-sequencing analysis of mouse lymph nodes and spleens after administration of an anti-oxycodone vaccine (OXY-sKLH) or carrier protein control (sKLH) with and without concurrent antibody-based depletion of interleukin-4 (IL-4)
2020-08-31 | GSE157144 | GEO
Project description:OBJECTIVES:The US opioid medication epidemic has resulted in serious health consequences for patients. Formulary management tools adopted by payers, specifically prior authorization (PA) policies, may lower the rates of opioid medication abuse and overdose. We compared rates of opioid abuse and overdose among enrollees in plans that varied in their use of PA from "High PA" (ie, required PA for 17 to 74 opioids), with "Low PA" (ie, required PA for 1 opioid), and "No PA" policies for opioid medications. STUDY DESIGN:Retrospective cohort study of patients initiating opioid treatment in Pennsylvania Medicaid from 2010 to 2012. METHODS:Generalized linear models with generalized estimating equations were employed to assess the relationships between the presence of PA policies and opioid medication abuse and overdose, as measured in Medicaid claims data, adjusting for demographics, comorbid health conditions, benzodiazepine/muscle relaxant use, and emergency department use. RESULTS:The study cohort included 297,634 enrollees with a total of 382,828 opioid treatment episodes. Compared with plans with No PA, enrollees in High PA (adjusted rate ratio [ARR], 0.89; 95% confidence interval [CI], 0.85-0.93; P <.001) and Low PA plans (ARR, 0.93; 95% CI, 0.87-1.00; P = .04) had lower rates of abuse. Enrollees in the Low PA plan had a lower rate of overdose than those within plans with No PA (ARR, 0.75; 95% CI, 0.59-0.95; P = .02). High PA plan enrollees were also less likely than No PA enrollees to experience an overdose, but this association was not statistically significant (ARR, 0.88; 95% CI, 0.76-1.02; P = .08). CONCLUSIONS:Enrollees within Medicaid plans that utilize PA policies appear to have lower rates of abuse and overdose following initiation of opioid medication treatment.
| S-EPMC6719534 | biostudies-literature
Project description:The objectives were to analyze the knowledge about overdose prevention, the use of naloxone, and the number of fatal overdoses after the implementation of Systematic Training in Overdose Prevention (STOOP) program. We conducted a quasi-experimental study, and held face-to-face interviews before (n = 725) and after (n = 722) implementation of systematic training in two different samples of people who injected opioids attending harm reduction centers. We asked participants to list the main causes of overdose and the main actions that should be taken when witnessing an overdose. We created two dependent variables, the number of (a) correct and (b) incorrect answers. The main independent variable was Study Group: Intervention Group (IG), Comparison Group (CG), Pre-Intervention Group With Sporadic Training in Overdose Prevention (PREIGS), or Pre-Intervention Group Without Training in Overdose Prevention (PREIGW). The relationship between the dependent and independent variables was assessed using a multivariate Poisson regression analysis. Finally, we conducted an interrupted time series analysis of monthly fatal overdoses before and after the implementation of systematic program during the period 2006-2015. Knowledge of overdose prevention increased after implementing systematic training program. Compared to the PREIGW, the IG gave more correct answers (IRR = 1.40;95%CI:1.33-1.47), and fewer incorrect answers (IRR = 0.33;95%CI:0.25-0.44). Forty percent of people who injected opioids who received a naloxone kit had used the kit in response to an overdose they witnessed. These courses increase knowledge of overdose prevention in people who use opioids, give them the necessary skills to use naloxone, and slightly diminish the number of fatal opioid overdoses in the city of Barcelona.
| S-EPMC5663400 | biostudies-literature
Project description:Opioid use disorders (OUD) affect over 27 million people worldwide. Anti-opioid vaccines offer a promising strategy to treat OUD and prevent overdose. Using immunomodulation of cytokine signaling to increase vaccine efficacy, this study found that blocking IL-4 improved the efficacy of vaccines targeting oxycodone and fentanyl in male and female mice. Genetic deletion of the IL-4 receptor, STAT6, or antibody-based depletion of IL-13, did not increase vaccine efficacy against opioids, suggesting the involvement of type I IL-4 receptors. Enhancement of vaccine efficacy with blockade of IL-4 was associated with improved germinal center formation in secondary lymphoid organs and selective transcriptome signatures in the activated CD4+ T cell population subset. These data suggest that IL-4 is both a pharmacological target and a potential biomarker of vaccine efficacy against OUD.
| S-EPMC7578047 | biostudies-literature
Project description:ImportanceIt is important to understand the magnitude and distribution of the economic burden of prescription opioid overdose, abuse, and dependence to inform clinical practice, research, and other decision makers. Decision makers choosing approaches to address this epidemic need cost information to evaluate the cost effectiveness of their choices.ObjectiveTo estimate the economic burden of prescription opioid overdose, abuse, and dependence from a societal perspective.Design, setting, and participantsIncidence of fatal prescription opioid overdose from the National Vital Statistics System, prevalence of abuse and dependence from the National Survey of Drug Use and Health. Fatal data are for the US population, nonfatal data are a nationally representative sample of the US civilian noninstitutionalized population ages 12 and older. Cost data are from various sources including health care claims data from the Truven Health MarketScan Research Databases, and cost of fatal cases from the WISQARS (Web-based Injury Statistics Query and Reporting System) cost module. Criminal justice costs were derived from the Justice Expenditure and Employment Extracts published by the Department of Justice. Estimates of lost productivity were based on a previously published study.ExposureCalendar year 2013.Main outcomes and measuresMonetized burden of fatal overdose and abuse and dependence of prescription opioids.ResultsThe total economic burden is estimated to be $78.5 billion. Over one third of this amount is due to increased health care and substance abuse treatment costs ($28.9 billion). Approximately one quarter of the cost is borne by the public sector in health care, substance abuse treatment, and criminal justice costs.Conclusions and relevanceThese estimates can assist decision makers in understanding the magnitude of adverse health outcomes associated with prescription opioid use such as overdose, abuse, and dependence.
| S-EPMC5975355 | biostudies-literature
Project description:BACKGROUND:Opioid overdose is a major and increasing cause of injury and death. There is an urgent need for interventions to reduce overdose events among high-risk persons. METHODS:Adults at elevated risk for opioid overdose involving heroin or pharmaceutical opioids who had been cared for in an emergency department (ED) were randomised to overdose education combined with a brief behavioural intervention and take-home naloxone or usual care. Outcomes included: (1) time to first opioid overdose-related event resulting in medical attention or death using competing risks survival analysis; and (2) ED visit and hospitalisation rates, using negative binomial regression and adjusting for time at risk. RESULTS:During the follow-up period, 24% of the 241 participants had at least one overdose event, 85% had one or more ED visits and 55% had at least one hospitalisation, with no significant differences between intervention and comparison groups. The instantaneous risk of an overdose event was not significantly lower for the intervention group (sub-HR: 0.83; 95%?CI 0.49 to 1.40). DISCUSSION:These null findings may be due in part to the severity of the population in terms of housing insecurity (70% impermanently housed), drug use, unemployment and acute healthcare issues. Given the high overdose and healthcare utilisation rates, more intensive interventions, such as direct referral and provision of housing and opioid agonist treatment medications, may be necessary to have a substantial impact on opioid overdoses for this high-acuity population in acute care settings. TRIAL REGISTRATION NUMBER:NCT0178830; Results.
| S-EPMC6800078 | biostudies-literature
Project description:BackgroundHospitalizations related to the consequences of opioid use are rising. National guidelines directing in-hospital opioid use disorder (OUD) management do not exist. OUD treatment guidelines intended for other treatment settings could inform in-hospital OUD management.ObjectiveEvaluate the quality and content of existing guidelines for OUD treatment and management.Data sourcesOVID MEDLINE, PubMed, Ovid PsychINFO, EBSCOhost CINHAL, ERCI Guidelines Trust, websites of relevant societies and advocacy organizations, and selected international search engines.Study selectionGuidelines published between January 2010 to June 2020 addressing OUD treatment, opioid withdrawal management, opioid overdose prevention, and care transitions among adults.Data extractionWe assessed quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.Data synthesisNineteen guidelines met the selection criteria. Most recommendations were based on observational studies or expert consensus. Guidelines recommended the use of nonstigmatizing language among patients with OUD; to assess patients with unhealthy opioid use for OUD using the Diagnostic Statistical Manual of Diseases-5th Edition criteria; use of methadone or buprenorphine to treat OUD and opioid withdrawal; use of multimodal, nonopioid therapy, and when needed, short-acting opioid analgesics in addition to buprenorphine or methadone, for acute pain management; ensuring linkage to ongoing methadone or buprenorphine treatment; referring patients to psychosocial treatment; and ensuring access to naloxone for opioid overdose reversal.ConclusionsIncluded guidelines were informed by studies with various levels of rigor and quality. Future research should systematically study buprenorphine and methadone initiation and titration among people using fentanyl and people with pain, especially during hospitalization.
| S-EPMC9474657 | 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:BACKGROUND:Evaluations of overdose response programs suggest effectiveness in preventing overdose-related death and individual willingness to respond to an overdose. However, knowledge of and confidence in performing response behaviors is necessary for individuals to intervene. This study assessed overdose responding self-efficacy among adults who reported lifetime opioid use. METHODS:Data come from a cross-sectional survey, part of a randomized controlled trial designed for adults living with hepatitis C. Participants were 18 years old or older, and reported lifetime opioid use. Overdose responding self-efficacy was assessed by perceived knowledge and/or need for additional training to have confidence responding to an overdose. Univariate statistics were calculated for overdose responding self-efficacy, and individual characteristics and experiences. Adjusted logistic regression was used to identify variables associated with low overdose responding self-efficacy. RESULTS:Of the 424 participants, 67.2% reported low overdose responding self-efficacy. Sixty percent witnessed and 30.4% experienced an overdose in the past year. Witnessing an overdose in the past year, experience with naloxone training, and receiving and using naloxone were associated with high overdose responding self-efficacy. While, apprehension with particular response behaviors (e.g. rescue breathing) was associated with low overdose responding self-efficacy. CONCLUSIONS:A large proportion of adults who reported lifetime opioid use did not feel confident or knowledgeable responding to an overdose. This could be influenced by overdose exposure, specific response behaviors, and response trainings.
| S-EPMC6699739 | biostudies-literature
Project description:ObjectiveTo address the opioid overdose epidemic, it is important to understand the broad scope of efforts under way in states, particularly states in which the rate of opioid-involved overdose deaths is declining. The primary objective of this study was to examine core elements of overdose prevention activities in 4 states with a high rate of opioid-involved overdose deaths that experienced a decrease in opioid-involved overdose deaths from 2016 to 2017.MethodsWe identified 5 states experiencing decreases in age-adjusted mortality rates for opioid-involved overdoses from 2016 to 2017 and examined their overdose prevention programs via program narratives developed with collaborators from each state's overdose prevention program. These program narratives used 10 predetermined categories to organize activities: legislative policies; strategic planning; data access, capacity, and dissemination; capacity building; public-facing resources (eg, web-based dashboards); training resources; enhancements and improvements to prescription drug monitoring programs; linkage to care; treatment; and community-focused initiatives. Using qualitative thematic analysis techniques, core elements and context-specific activities emerged.ResultsIn the predetermined categories of programmatic activities, we identified the following core elements of overdose prevention and response: comprehensive state policies; strategic planning; local engagement; data access, capacity, and dissemination; training of professional audiences (eg, prescribers); treatment infrastructure; and harm reduction.ConclusionsThe identification of core elements and context-specific activities underscores the importance of implementation and adaptation of evidence-based prevention strategies, interdisciplinary partnerships, and collaborations to address opioid overdose. Further evaluation of these state programs and other overdose prevention efforts in states where mortality rates for opioid-involved overdoses declined should focus on impact, optimal timing, and combinations of program activities during the life span of an overdose prevention program.
| S-EPMC9257511 | biostudies-literature