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      Opioid-related overdose and chronic use following an initial prescription of hydrocodone versus oxycodone

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          Abstract

          Background

          Hydrocodone and oxycodone are prescribed commonly to treat pain. However, differences in risk of opioid-related adverse outcomes after an initial prescription are unknown.

          This study aims to determine the risk of opioid-related adverse events, defined as either chronic use or opioid overdose, following a first prescription of hydrocodone or oxycodone to opioid naïve patients.

          Methods

          A retrospective analysis of multiple linked public health datasets in the state of Oregon. Adult patients ages 18 and older who a) received an initial prescription for oxycodone or hydrocodone between 2015–2017 and b) had no opioid prescriptions or opioid-related hospitalizations or emergency department visits in the year preceding the prescription were followed through the end of 2018. First-year chronic opioid use was defined as ≥6 opioid prescriptions (including index) and average ≤30 days uncovered between prescriptions. Fatal or non-fatal opioid overdose was indicated from insurance claims, hospital discharge data or vital records.

          Results

          After index prescription, 2.8% (n = 14,458) of individuals developed chronic use and 0.3% (n = 1,480) experienced overdose. After adjustment for patient and index prescription characteristics, patients receiving oxycodone had lower odds of developing chronic use relative to patients receiving hydrocodone (adjusted odds ratio = 0.95, 95% confidence interval (CI) 0.91–1.00) but a higher risk of overdose (adjusted hazard ratio (aHR) = 1.65, 95% CI 1.45–1.87). Oxycodone monotherapy appears to greatly increase the hazard of opioid overdose (aHR 2.18, 95% CI 1.86–2.57) compared with hydrocodone with acetaminophen. Oxycodone combined with acetaminophen also shows a significant increase (aHR 1.26, 95% CI 1.06–1.50), but not to the same extent.

          Conclusions

          Among previously opioid-naïve patients, the risk of developing chronic use was slightly higher with hydrocodone, whereas the risk of overdose was higher after oxycodone, in combination with acetaminophen or monotherapy. With a goal of reducing overdose-related deaths, hydrocodone may be the favorable agent.

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          Most cited references27

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          Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples

          The propensity score is a subject's probability of treatment, conditional on observed baseline covariates. Conditional on the true propensity score, treated and untreated subjects have similar distributions of observed baseline covariates. Propensity-score matching is a popular method of using the propensity score in the medical literature. Using this approach, matched sets of treated and untreated subjects with similar values of the propensity score are formed. Inferences about treatment effect made using propensity-score matching are valid only if, in the matched sample, treated and untreated subjects have similar distributions of measured baseline covariates. In this paper we discuss the following methods for assessing whether the propensity score model has been correctly specified: comparing means and prevalences of baseline characteristics using standardized differences; ratios comparing the variance of continuous covariates between treated and untreated subjects; comparison of higher order moments and interactions; five-number summaries; and graphical methods such as quantile–quantile plots, side-by-side boxplots, and non-parametric density plots for comparing the distribution of baseline covariates between treatment groups. We describe methods to determine the sampling distribution of the standardized difference when the true standardized difference is equal to zero, thereby allowing one to determine the range of standardized differences that are plausible with the propensity score model having been correctly specified. We highlight the limitations of some previously used methods for assessing the adequacy of the specification of the propensity-score model. In particular, methods based on comparing the distribution of the estimated propensity score between treated and untreated subjects are uninformative. Copyright © 2009 John Wiley & Sons, Ltd.
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            CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016.

            Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose.
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              The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop.

              Increases in prescriptions of opioid medications for chronic pain have been accompanied by increases in opioid overdoses, abuse, and other harms and uncertainty about long-term effectiveness.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
                Role: Funding acquisitionRole: Writing – review & editing
                Role: Project administrationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Funding acquisitionRole: MethodologyRole: Writing – review & editing
                Role: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 April 2022
                2022
                : 17
                : 4
                : e0266561
                Affiliations
                [1 ] Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America
                [2 ] Harvard Medical School, Boston, Massachusetts, United States of America
                [3 ] Division of Research and Evaluation, Comagine Health, Portland, Oregon, United States of America
                [4 ] Department of Epidemiology and Biostatistics, School of Public Health, University of Nevada, Las Vegas, Las Vegas, Nevada, United States of America
                [5 ] Brandeis University, Waltham, Massachusetts, United States of America
                [6 ] Department of Psychiatry, McLean Hospital, Belmont, Massachusetts, United States of America
                [7 ] Department of Emergency Medicine, Ohio State University, Columbus, Ohio, United States of America
                [8 ] Department of Emergency Medicine Rutgers New Jersey Medical School, Newark, New Jersey, United States of America
                [9 ] Section of General Internal Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, United States of America
                St. Michael’s Hospital, CANADA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-4672-5184
                https://orcid.org/0000-0002-4685-164X
                Article
                PONE-D-21-33002
                10.1371/journal.pone.0266561
                8982846
                35381052
                6084fa3e-0397-456d-ac2a-200189a2b199
                © 2022 Weiner et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 October 2021
                : 22 March 2022
                Page count
                Figures: 0, Tables: 3, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000026, National Institute on Drug Abuse;
                Award ID: 5-R01-DA044167
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000133, Agency for Healthcare Research and Quality;
                Award ID: 5-R01-HS026753
                Award Recipient :
                National Institute on Drug Abuse 5-R01-DA044167 (SGW, MAH, SEI, GAR, SEH, CH, RDW, EWB, DPF, PWK) and Agency for Healthcare Research and Quality 5-R01-HS026753 (SGW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Analgesics
                Opioids
                Medicine and Health Sciences
                Pain Management
                Analgesics
                Opioids
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Opioids
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Analgesics
                Opioids
                Oxycodone
                Medicine and Health Sciences
                Pain Management
                Analgesics
                Opioids
                Oxycodone
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Opioids
                Oxycodone
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Analgesics
                Opioids
                Hydrocodone
                Medicine and Health Sciences
                Pain Management
                Analgesics
                Opioids
                Hydrocodone
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Opioids
                Hydrocodone
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Social Sciences
                Economics
                Health Economics
                Health Insurance
                Medicine and Health Sciences
                Health Care
                Health Economics
                Health Insurance
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Pain
                People and places
                Geographical locations
                North America
                United States
                Oregon
                Social Sciences
                Political Science
                Public Policy
                Medicare
                Custom metadata
                Data cannot be shared publicly because of data use limitations. The data underlying the results presented in the study are available from the Oregon Health Authority Public Health Division at phone number 971-673-1222 or email health.webmaster@ 123456dhsoha.state.or.us .

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