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      Long-term opioid use and mortality in patients with chronic non-cancer pain: Ten-year follow-up study in South Korea from 2010 through 2019

      research-article
      a , b , 1 , c , 1 , a , b , *
      eClinicalMedicine
      Elsevier
      Analgesics, Opioid, Mortality, Pain, Population, Cohort studies

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          Summary

          Background

          We aimed to investigate the prevalence and factors associated with long-term opioid use among patients with chronic non-cancer pain (CNCP).

          Methods

          We extracted data from the National Health Insurance Service (NHIS) database in South Korea. As a nationwide database, the NHIS database contains information regarding all disease diagnoses and prescriptions for any drug and/or procedures. A total of 2.5% of adult patients (≥20 years of age) who were diagnosed with musculoskeletal diseases and CNCP from 2010 to 2019 were selected using a stratified random sampling technique and included in the analysis. Patients who were prescribed opioids continuously for ≥90 days were classified as long-term opioid users.

          Findings

          A total of 19,645,161 patients with CNCP were included in the final analysis. The prevalence of long-term opioid use was 0.47% (95% confidence interval [CI]: 0.46%, 0.48%; 8421/1,808,043) in 2010, which gradually increased to 2.63% (95% CI: 2.61%, 2.66%; 49,846/1,892,913) in 2019. Among the 2010 cohort ( n = 1,804,019), in multivariable logistic regression: old age, underlying disability, increased Charlson comorbidity index, use of benzodiazepine or Z-drug, rheumatoid arthritis, osteoarthritis, and low back pain were associated with an increased prevalence of long-term opioid use among patients with CNCP. In a multivariable Cox regression, the 10-year all-cause mortality in long-term opioid users was found to be 1·21-fold (hazard ratio: 1.21, 95% CI: 1.13, 1.31; P<0·001) higher than that in opioid-naive patients with CNCP.

          Interpretation

          Long-term opioid use increased in patients with CNCP in South Korea from 2010 to 2019. Certain factors were potential risk factors for long-term opioid use. Moreover, long-term opioid use was associated with increased 10-year all-cause mortality among patients with CNCP.

          Funding

          None.

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          Most cited references36

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          The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies.

          Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the Web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.
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            Prescription Opioid Use, Misuse, and Use Disorders in U.S. Adults: 2015 National Survey on Drug Use and Health

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              Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015.

              The U.S. opioid epidemic is continuing, and drug overdose deaths nearly tripled during 1999-2014. Among 47,055 drug overdose deaths that occurred in 2014 in the United States, 28,647 (60.9%) involved an opioid (1). Illicit opioids are contributing to the increase in opioid overdose deaths (2,3). In an effort to target prevention strategies to address the rapidly changing epidemic, CDC examined overall drug overdose death rates during 2010-2015 and opioid overdose death rates during 2014-2015 by subcategories (natural/semisynthetic opioids, methadone, heroin, and synthetic opioids other than methadone).* Rates were stratified by demographics, region, and by 28 states with high quality reporting on death certificates of specific drugs involved in overdose deaths. During 2015, drug overdoses accounted for 52,404 U.S. deaths, including 33,091 (63.1%) that involved an opioid. There has been progress in preventing methadone deaths, and death rates declined by 9.1%. However, rates of deaths involving other opioids, specifically heroin and synthetic opioids other than methadone (likely driven primarily by illicitly manufactured fentanyl) (2,3), increased sharply overall and across many states. A multifaceted, collaborative public health and law enforcement approach is urgently needed. Response efforts include implementing the CDC Guideline for Prescribing Opioids for Chronic Pain (4), improving access to and use of prescription drug monitoring programs, enhancing naloxone distribution and other harm reduction approaches, increasing opioid use disorder treatment capacity, improving linkage into treatment, and supporting law enforcement strategies to reduce the illicit opioid supply.
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                Author and article information

                Contributors
                Journal
                eClinicalMedicine
                EClinicalMedicine
                eClinicalMedicine
                Elsevier
                2589-5370
                18 July 2022
                September 2022
                18 July 2022
                : 51
                : 101558
                Affiliations
                [a ]Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
                [b ]Department of Anesthesiology and Pain Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea
                [c ]Department of Anesthesiology and Pain Medicine, Inje University Seoul Paik Hospital, Seoul, Republic of Korea
                Author notes
                [* ]Corresponding author at: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Gumi-ro, 173, Beon-gil, Bundang-gu, Seongnam, 13620, South Korea; Department of Anesthesiology and Pain Medicine, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea. airohtak@ 123456hotmail.com
                [1]

                Equal contributions as co-first authors.

                Article
                S2589-5370(22)00288-7 101558
                10.1016/j.eclinm.2022.101558
                9304910
                35875817
                bc7a59d0-ea11-460a-b2ac-cf4c4720ea5d
                © 2022 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 12 April 2022
                : 23 June 2022
                : 24 June 2022
                Categories
                Articles

                analgesics,opioid,mortality,pain,population,cohort studies
                analgesics, opioid, mortality, pain, population, cohort studies

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