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      Sex differences in high opioid dose escalation among Malaysian patients with long term opioid therapy

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          Abstract

          Purpose: This study evaluated the risk of opioid dose escalation as it relates to sex differences among patients receiving opioids for long-term therapy.

          Patients and methods: This retrospective cohort study was conducted in tertiary hospital settings in Malaysia using electronic prescription records. Opioid naïve patients, aged ≥18 years, who were undergoing long-term opioid therapy of ≥90 days, with at least one opioid prescription (buprenorphine, morphine, oxycodone, fentanyl, dihydrocodeine or tramadol) between 1st January 2011 and 31st December 2016, were included in the study. They were followed until (i) the end of the study period, (ii) death from any cause or (iii) discontinuation of therapy from their first opioid prescription without any intervals of ≥120 days between successive prescriptions. The risk of high opioid dose escalation to ≥100 mg/day and ≥200 mg/day relative to men and women was measured.

          Results: A total of 4688 patients (58.8% women, 41.3% men) on long-term opioid therapy were identified. Among these patients, 248 (5.29%) were escalated to high opioid doses of ≥100 mg/day and 69 (1.47%) were escalated to ≥200 mg/day. The escalation to high-dose opioid therapy was more likely to occur in men than in women, even after adjustment for age (dose ≥100 mg/day [adjusted hazard ratio 2.32; 95% confidence interval (CI), 1.79 to 3.00; p<0.0001] and ≥200 mg/day [adjusted hazard ratio 6.10; 95% CI, 3.39 to 10.98; p<0.0001]).

          Conclusion: The risk of opioid dose escalation differed between men and women, as men were at higher risk than women for high opioid dose escalation.

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          Most cited references 15

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          Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain.

          Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related policies. Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel after a systematic review of the evidence.
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            Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis.

            Opioid use in chronic pain treatment is complex, as patients may derive both benefit and harm. Identification of individuals currently using opioids in a problematic way is important given the substantial recent increases in prescription rates and consequent increases in morbidity and mortality. The present review provides updated and expanded information regarding rates of problematic opioid use in chronic pain. Because previous reviews have indicated substantial variability in this literature, several steps were taken to enhance precision and utility. First, problematic use was coded using explicitly defined terms, referring to different patterns of use (ie, misuse, abuse, and addiction). Second, average prevalence rates were calculated and weighted by sample size and study quality. Third, the influence of differences in study methodology was examined. In total, data from 38 studies were included. Rates of problematic use were quite broad, ranging from <1% to 81% across studies. Across most calculations, rates of misuse averaged between 21% and 29% (range, 95% confidence interval [CI]: 13%-38%). Rates of addiction averaged between 8% and 12% (range, 95% CI: 3%-17%). Abuse was reported in only a single study. Only 1 difference emerged when study methods were examined, where rates of addiction were lower in studies that identified prevalence assessment as a primary, rather than secondary, objective. Although significant variability remains in this literature, this review provides guidance regarding possible average rates of opioid misuse and addiction and also highlights areas in need of further clarification.
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              Age and gender trends in long-term opioid analgesic use for noncancer pain.

              We describe age and gender trends in long-term use of prescribed opioids for chronic noncancer pain in 2 large health plans. Age- and gender-standardized incident (beginning in each year) and prevalent (ongoing) opioid use episodes were estimated with automated health care data from 1997 to 2005. Profiles of opioid use in 2005 by age and gender were also compared. From 1997 to 2005, age-gender groups exhibited a total percentage increase ranging from 16% to 87% for incident long-term opioid use and from 61% to 135% for prevalent long-term opioid use. Women had higher opioid use than did men. Older women had the highest prevalence of long-term opioid use (8%-9% in 2005). Concurrent use of sedative-hypnotic drugs and opioids was common, particularly among women. Risks and benefits of long-term opioid use are poorly understood, particularly among older adults. Increased surveillance of the safety of long-term opioid use is needed in community practice settings.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                JPR
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                24 April 2019
                2019
                : 12
                : 1251-1257
                Affiliations
                [1 ]Kulliyah of Pharmacy, International Islamic University Malaysia, Kuantan Campus , 25200 Kuantan, Pahang, Malaysia
                [2 ]Hospital Selayang, Lebuhraya Selayang-Kepong , 68100 Batu Caves, Selangor Darul Ehsan, Malaysia
                Author notes
                Correspondence: Che Suraya ZinKulliyyah of Pharmacy, International Islamic University Malaysia , Kuantan Campus, Kuantan25200, Pahang, MalaysiaTel +609 570 4909Fax +609 571 6775Email chesuraya@ 123456iium.edu.my
                Article
                199243
                10.2147/JPR.S199243
                6499483
                © 2019 Zin et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 2, Tables: 2, References: 28, Pages: 7
                Categories
                Original Research

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