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      Comparison of Two Different Analgesic Prescription Strategies and Healthcare Systems: Slovenia vs. the Netherlands

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          Abstract

          Background: Prescribing practice of pain medication is changing in the Netherlands; opioids are used more often instead of nonsteroidal anti-inflammatory drugs (NSAIDs), therefore we aimed to compare the use of pain medication with Slovenia which has stringent prescribing rules for strong opioids.

          Methods: We conducted a cohort study into national prescription databases of the Netherlands and Slovenia covering pharmacy claims between January 1, 2013 and December 31, 2019. In the analysis about 17 million Dutch and 2 million Slovenian residents were included.

          Findings: The use of opioids and NSAIDs was higher in Slovenia than in the Netherlands. More frequent use of opioids in Slovenia could be almost entirely explained by weak opioids (about 6% of the population), whereas they were prescribed 50% less frequently in the Netherlands. The opioid use has increased by about 20% in the Netherlands (4.85 and 6.00% of the population in 2013 and 2018, respectively), and the majority of this increase could be explained by strong opioids (4.05% in 2018), specifically, by oxycodone whose use increased by more than 2-fold between 2013 and 2019. In comparison, oxycodone was seldomly used in Slovenia (about 0.3% of the population received a prescription in a year).

          Interpretation: When medication use is controlled by stringent prescribing rules, like for strong opioids in Slovenia, the use is lower as compared to when such rules do not exist.

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          Most cited references20

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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 promotion and marketing of oxycontin: commercial triumph, public health tragedy.

            I focus on issues surrounding the promotion and marketing of controlled drugs and their regulatory oversight. Compared with noncontrolled drugs, controlled drugs, with their potential for abuse and diversion, pose different public health risks when they are overpromoted and highly prescribed. An in-depth analysis of the promotion and marketing of OxyContin illustrates some of the associated issues. Modifications of the promotion and marketing of controlled drugs by the pharmaceutical industry and an enhanced capacity of the Food and Drug Administration to regulate and monitor such promotion can have a positive impact on the public health.
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              Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data

              Objective To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs (NSAIDs). Design Systematic review followed by a one stage bayesian individual patient data meta-analysis. Data sources Studies from Canadian and European healthcare databases. Review methods Eligible studies were sourced from computerised drug prescription or medical databases, conducted in the general or an elderly population, documented acute myocardial infarction as specific outcome, studied selective cyclo-oxygenase-2 inhibitors (including rofecoxib) and traditional NSAIDs, compared risk of acute myocardial infarction in NSAID users with non-users, allowed for time dependent analyses, and minimised effects of confounding and misclassification bias. Exposure and outcomes Drug exposure was modelled as an indicator variable incorporating the specific NSAID, its recency, duration of use, and dose. The outcome measures were the summary adjusted odds ratios of first acute myocardial infarction after study entry for each category of NSAID use at index date (date of acute myocardial infarction for cases, matched date for controls) versus non-use in the preceding year and the posterior probability of acute myocardial infarction. Results A cohort of 446 763 individuals including 61 460 with acute myocardial infarction was acquired. Taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of myocardial infarction. With use for one to seven days the probability of increased myocardial infarction risk (posterior probability of odds ratio >1.0) was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. The corresponding odds ratios (95% credible intervals) were 1.24 (0.91 to 1.82) for celecoxib, 1.48 (1.00 to 2.26) for ibuprofen, 1.50 (1.06 to 2.04) for diclofenac, 1.53 (1.07 to 2.33) for naproxen, and 1.58 (1.07 to 2.17) for rofecoxib. Greater risk of myocardial infarction was documented for higher dose of NSAIDs. With use for longer than one month, risks did not appear to exceed those associated with shorter durations. Conclusions All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses.
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                Author and article information

                Contributors
                Journal
                Front Pain Res (Lausanne)
                Front Pain Res (Lausanne)
                Front. Pain Res.
                Frontiers in Pain Research
                Frontiers Media S.A.
                2673-561X
                2673-561X
                27 August 2021
                2021
                : 2
                : 723797
                Affiliations
                [1] 1Department of Clinical Epidemiology, Leiden University Medical Center , Leiden, Netherlands
                [2] 2Department of Anesthesiology, Leiden University Medical Center , Leiden, Netherlands
                [3] 3Health Insurance Institute of Slovenia , Ljubljana, Slovenia
                Author notes

                Edited by: Aubin Moutal, University of Arizona, United States

                Reviewed by: Mohab Ibrahim, University of Arizona, United States; Célian Bertin, Université Clermont Auvergne, France

                *Correspondence: Ajda Bedene a.bedene@ 123456lumc.nl

                This article was submitted to Pharmacological Treatment of Pain, a section of the journal Frontiers in Pain Research

                Article
                10.3389/fpain.2021.723797
                8915570
                da27015b-aba1-432d-9b76-5ab57fb2a914
                Copyright © 2021 Bedene, Strmljan, van Dorp, Udovič, Lijfering, Niesters, Rosendaal, Dahan and Fürst.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 June 2021
                : 05 August 2021
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 36, Pages: 9, Words: 5951
                Funding
                Funded by: Nederlandse Organisatie voor Wetenschappelijk Onderzoek, doi 10.13039/501100003246;
                Award ID: NWA.1160.18.300
                Categories
                Pain Research
                Original Research

                pain medication,opioid epidemic,pain management,prescription guidelines,european guidelines

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