Dataset Information

Combating escalating harms associated with pharmaceutical opioid use in Australia: the POPPY II study protocol.

ABSTRACT:

Introduction

Opioid prescribing has increased 15-fold in Australia in the past two decades, alongside increases in a range of opioid-related harms such as opioid dependence and overdose. However, despite concerns about increasing opioid use, extramedical use and harms, there is a lack of population-level evidence about the drivers of long-term prescribed opioid use, dependence, overdose and other harms.

Methods and analysis

We will form a cohort of all adult residents in New South Wales (NSW), Australia, who initiated prescribed opioids from 2002 using Pharmaceutical Benefits Scheme dispensing records. This cohort will be linked to a wide range of other datasets containing information on sociodemographic and clinical characteristics, health service use and adverse outcomes (eg, opioid dependence and non-fatal and fatal overdose). Analyses will initially examine patterns and predictors of prescribed opioid use and then apply regression and survival analysis to quantify the risks and risk factors of adverse outcomes associated with prescribed opioid use.

Ethics and dissemination

This study has received full ethical approval from the Australian Institute of Health and Welfare Ethics Committee, the NSW Population and Health Services Research Committee and the ACT Health Human Research Ethics Committee. This will be the largest postmarketing surveillance study of prescribed opioids undertaken in Australia, linking exposure and outcomes and examining risk factors for adverse outcomes of prescribed opioids. As such, this work has important translational promise, with direct relevance to regulatory authorities and agencies worldwide. Project findings will be disseminated at scientific conferences and in peer-reviewed journals. We will also conduct targeted dissemination with policy makers, professional bodies and peak bodies in the pain, medicine and addiction fields through stakeholder workshops and advisory groups. Results will be reported in accordance with the REporting of studies Conducted using Observational Routinely collected Data (RECORD) Statement.

SUBMITTER: Gisev N

PROVIDER: S-EPMC6286479 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Combating escalating harms associated with pharmaceutical opioid use in Australia: the POPPY II study protocol.

Gisev Natasa N Pearson Sallie-Anne SA Dobbins Timothy T Currow David C DC Blyth Fiona F Larney Sarah S Dunlop Adrian A Mattick Richard P RP Wilson Andrew A Degenhardt Louisa L

BMJ open 20181204 12

<h4>Introduction</h4>Opioid prescribing has increased 15-fold in Australia in the past two decades, alongside increases in a range of opioid-related harms such as opioid dependence and overdose. However, despite concerns about increasing opioid use, extramedical use and harms, there is a lack of population-level evidence about the drivers of long-term prescribed opioid use, dependence, overdose and other harms.<h4>Methods and analysis</h4>We will form a cohort of all adult residents in New South ...[more]

PMID: 30518593

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Project description:Background and aimsPharmaceutical opioids are a significant contributor to the global 'opioid crisis', yet few studies have comprehensively distinguished between opioid types. We measured whether a range of common pharmaceutical opioids varied in their contribution to the rates and characteristics of harm in a population-wide indicator of non-fatal overdose.DesignRetrospective observational study of emergency department (ED) patient care records in the Victorian Emergency Minimum Data set (VEMD), July 2009 to June 2019.SettingVictoria, Australia.CasesED presentations for non-fatal overdose related to pharmaceutical opioid use (n = 5403), where the specific pharmaceutical opioid was documented.MeasurementsWe compared harms across the nine individual pharmaceutical opioids most commonly sold, and considered where multiple opioids contributed to the overdose. We calculated supply-adjusted rates of ED presentations using Poisson regression and used multinomial logistic regression to compare demographic and clinical characteristics of presentations among nine distinct pharmaceutical opioids and a 10th category where multiple opioids were documented for the presentation.FindingsThere were wide differences, up to 27-fold, between supply-adjusted rates of overdose. When considering presentations with sole opioids, the highest supply-adjusted overdose rates [per 100 000 oral morphine equivalents (OME); 95% confidence interval (CI)] were for codeine (OME = 0.078, 95% CI = 0.073-0.08) and oxycodone (OME =0.029, 95% CI = 0.027-0.030) and the lowest were for tapentadol (OME = 0.004, 95% CI = 0.003-0.006) and fentanyl (OME = 0.003, 95% CI = 0.002-0.004). These rates appeared related to availability rather than opioid potency. Most (62%) poisonings involved females. Codeine, oxycodone and tramadol were associated with younger presentations (respectively, 59.5%, 41.7% and 49.8% of presentations were 12-34 years old), and intentional self-harm (respectively 65.2%, 50.6%, and 52.8% of presentations). Relative to morphine, fentanyl [ 0.32 relative risk ratio (RRR)] and methadone ( 0.58 RRR) presentations were less likely to be coded as self-harm. Relative to morphine-buprenorphine, codeine, oxycodone and tramadol presentations were significantly more likely to be associated with the less urgent triage categories (respectively 2.18, 1.80, 1.52, 1.65 RRR).ConclusionsIn Victoria, Australia, rates and characteristics of emergency department presentations for pharmaceutical opioids show distinct variations by opioid type.

Project description:Opioid abuse in the United States has been declared a national crisis and is exacerbated by an inexpensive, readily available, and illicit supply of synthetic opioids. Specifically, fentanyl and related analogues such as carfentanil pose a significant danger to opioid users due to their high potency and rapid acting depression of respiration. In recent years these synthetic opioids have become the number one cause of drug-related deaths. In our research efforts to combat the public health threat posed by synthetic opioids, we have developed monoclonal antibodies (mAbs) against the fentanyl class of drugs. The mAbs were generated in hybridomas derived from mice vaccinated with a fentanyl conjugate vaccine. Guided by a surface plasmon resonance (SPR) binding assay, we selected six hybridomas that produced mAbs with 10-11 M binding affinity for fentanyl, yet broad cross-reactivity with related fentanyl analogues. In mouse antinociception models, our lead mAb (6A4) could blunt the effects of both fentanyl and carfentanil in a dose-responsive manner. Additionally, mice pretreated with 6A4 displayed enhanced survival when subjected to fentanyl above LD50 doses. Pharmacokinetic analysis revealed that the antibody sequesters large amounts of these drugs in the blood, thus reducing drug biodistribution to the brain and other tissue. Lastly, the 6A4 mAb could effectively reverse fentanyl/carfentanil-induced antinociception comparable to the opioid antagonist naloxone, the standard of care drug for treating opioid overdose. While naloxone is known for its short half-life, we found the half-life of 6A4 to be approximately 6 days in mice, thus monoclonal antibodies could theoretically be useful in preventing renarcotization events in which opioid intoxication recurs following quick metabolism of naloxone. Our results as a whole demonstrate that monoclonal antibodies could be a desirable treatment modality for synthetic opioid overdose and possibly opioid use disorder.

Project description:Introduction and aimsExtramedical use of, and associated harms with pharmaceutical opioids are common. Analysis of coded ambulance clinical records provides a unique opportunity to examine a national population-level indicator of relative harms. This protocol describes an observational study with three aims: (1) to compare supply adjusted rates of pharmaceutical opioid-related ambulance attendances for buprenorphine, codeine, fentanyl, oxycodone, oxycodone-naloxone, morphine, pethidine, tramadol and tapentadol; (2) to compare presentation characteristics for these commonly used pharmaceutical opioids and (3) to describe the context surrounding ambulance presentations related to oxycodone, a widely used opioid with an established abuse liability, and tapentadol, a more recent 'atypical' opioid on the Australian market, with fewer studies that have directly examined signals of extramedical use.MethodTrained coders extract data from clinical records for ambulance presentations relating to extramedical use of commonly used pharmaceutical opioids. These data form the basis of a large, national database that captures alcohol-related and drug-related harms. Supply adjusted rates of presentations will be examined using Poisson regression. Multinomial logistic regression will be used to compare severity and other characteristics of attendances relating to different pharmaceutical opioids. Tapentadol-related and oxycodone-related cases will be qualitatively examined to understand the situationally specific contexts of the ambulance attendances outside of the characteristics captured in routinely coded variables.Ethics and disseminationEthics approval related to analysis of ambulance attendance data was obtained from the Eastern Health Human Research Ethics Committee (E122 08-09), with an amendment specific to the qualitative analysis. Findings will be submitted for peer review in 2019. The understanding of risk profiles in real-world settings is of international public health importance. The analysis and publication of findings from this national dataset of clinical records will provide one of the most nuanced analyses to date of relative harms across nine pharmaceutical opioids over a 6-year period.

Dataset Information

Combating escalating harms associated with pharmaceutical opioid use in Australia: the POPPY II study protocol.

Introduction

Methods and analysis

Ethics and dissemination

Publications

Combating escalating harms associated with pharmaceutical opioid use in Australia: the POPPY II study protocol.

Similar Datasets

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