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      The impact of chronic pain on opioid addiction treatment: a systematic review protocol

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          Abstract

          Background

          The consequences of opioid relapse among patients being treated with opioid substitution treatment (OST) are serious and can result in abnormal cardiovascular function, overdose, and mortality. Chronic pain is a major risk factor for opioid relapse within the addiction treatment setting. There exist a number of opioid maintenance therapies including methadone, buprenorphine, naltrexone, and levomethadyl acetate (LAAM), of which the mediating effects of pain on treatment attrition, substance use behavior, and social functioning may differ across therapies. We aim to 1) evaluate the impact of pain on the treatment outcomes of addiction patients being managed with OST and 2) identify the most recently published opioid maintenance treatment guidelines from the United States, Canada, and the UK to determine how the evidence is being translated into clinical practice.

          Methods/design

          The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, ProQuest Dissertations and theses Database, Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. We will search www.guidelines.gov and the National Institute for Care and Excellence (NICE) databases to identify the most recently published OST guidelines. All screening and data extraction will be completed in duplicate. Provided the data are suitable, we will perform a multiple treatment comparison using Bayesian meta-analytic methods to produce summary statistics estimating the effect of chronic pain on all OSTs. Our primary outcome is substance use behavior, which includes opioid and non-opioid substance use. We will also evaluate secondary endpoints such as treatment retention, general physical health, intervention adherence, personal and social functioning, as well as psychiatric symptoms.

          Discussion

          This review will capture the experience of treatment outcomes for a sub-population of opioid addiction patients and provide an opportunity to distinguish the best quality guidelines for OST. If chronic pain truly does result in negative consequences for opioid addiction patients, it is important we identify which OSTs are most appropriate for chronic pain patients as well as ensure the treatment guidelines incorporate this information.

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          Most cited references18

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          Improved tests for a random effects meta-regression with a single covariate.

          The explanation of heterogeneity plays an important role in meta-analysis. The random effects meta-regression model allows the inclusion of trial-specific covariates which may explain a part of the heterogeneity. We examine the commonly used tests on the parameters in the random effects meta-regression with one covariate and propose some new test statistics based on an improved estimator of the variance of the parameter estimates. The approximation of the distribution of the newly proposed tests is based on some theoretical considerations. Moreover, the newly proposed tests can easily be extended to the case of more than one covariate. In a simulation study, we compare the tests with regard to their actual significance level and we consider the log relative risk as the parameter of interest. Our simulation study reflects the meta-analysis of the efficacy of a vaccine for the prevention of tuberculosis originally discussed in Berkey et al. The simulation study shows that the newly proposed tests are superior to the commonly used test in holding the nominal significance level. Copyright 2003 John Wiley & Sons, Ltd.
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            A comprehensive review of opioid-induced hyperalgesia.

            Opioid-induced hyperalgesia (OIH) is defined as a state of nociceptive sensitization caused by exposure to opioids. The condition is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could actually become more sensitive to certain painful stimuli. The type of pain experienced might be the same as the underlying pain or might be different from the original underlying pain. OIH appears to be a distinct, definable, and characteristic phenomenon that could explain loss of opioid efficacy in some patients. Findings of the clinical prevalence of OIH are not available. However, several observational, cross-sectional, and prospective controlled trials have examined the expression and potential clinical significance of OIH in humans. Most studies have been conducted using several distinct cohorts and methodologies utilizing former opioid addicts on methadone maintenance therapy, perioperative exposure to opioids in patients undergoing surgery, and healthy human volunteers after acute opioid exposure using human experimental pain testing. The precise molecular mechanism of OIH, while not yet understood, varies substantially in the basic science literature, as well as clinical medicine. It is generally thought to result from neuroplastic changes in the peripheral and central nervous system (CNS) that lead to sensitization of pronociceptive pathways. While there are many proposed mechanisms for OIH, 5 mechanisms involving the central glutaminergic system, spinal dynorphins, descending facilitation, genetic mechanisms, and decreased reuptake and enhanced nociceptive response have been described as the important mechanisms. Of these, the central glutaminergic system is considered the most common possibility. Another is the hypothesis that N-methyl-D-aspartate (NMDA) receptors in OIH include activation, inhibition of the glutamate transporter system, facilitation of calcium regulated intracellular protein kinase C, and cross talk of neural mechanisms of pain and tolerance. Clinicians should suspect OIH when opioid treatment's effect seems to wane in the absence of disease progression, particularly if found in the context of unexplained pain reports or diffuse allodynia unassociated with the original pain, and increased levels of pain with increasing dosages. The treatment involves reducing the opioid dosage, tapering them off, or supplementation with NMDA receptor modulators. This comprehensive review addresses terminology and definition, prevalence, the evidence for mechanism and physiology with analysis of various factors leading to OIH, and effective strategies for preventing, reversing, or managing OIH.
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              Trends in use of opioids for non-cancer pain conditions 2000-2005 in commercial and Medicaid insurance plans: the TROUP study.

              Opioids are widely prescribed for non-cancer pain conditions (NCPC), but there have been no large observational studies in actual clinical practice assessing patterns of opioid use over extended periods of time. The TROUP (Trends and Risks of Opioid Use for Pain) study reports on trends in opioid therapy for NCPC in two disparate populations, one national and commercially insured population (HealthCore plan data) and one state-based and publicly-insured (Arkansas Medicaid) population over a six year period (2000-2005). We track enrollees with the four most common NCPC conditions: arthritis/joint pain, back pain, neck pain, headaches, as well as HIV/AIDS. Rates of NCPC diagnosis and opioid use increased linearly during this period in both groups, with the Medicaid group starting at higher rates and the HealthCore group increasing more rapidly. The proportion of enrollees receiving NCPC diagnoses increased (HealthCore 33%, Medicaid 9%), as did the proportion of enrollees with NCPC diagnoses who received opioids (HealthCore 58%, Medicaid 29%). Cumulative yearly opioid dose (in mg. morphine equivalents) received by NCPC patients treated with opioids increased (HealthCore 38%, Medicaid 37%) due to increases in number of days supplied rather than dose per day supplied. Use of short-acting Drug Enforcement Administration Schedule II opioids increased most rapidly, both in proportion of NCPC patients treated (HealthCore 54%, Medicaid 38%) and in cumulative yearly dose (HealthCore 95%, Medicaid 191%). These trends have occurred without any significant change in the underlying population prevalence of NCPC or new evidence of the efficacy of long-term opioid therapy and thus likely represent a broad-based shift in opioid treatment philosophy.
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                Author and article information

                Contributors
                dennisbb@mcmaster.ca
                baworm@mcmaster.ca
                paulj@mcmaster.ca
                mvarenbut@canatc.ca
                jdaiter@canatc.ca
                cplater@toxpro.ca
                pareg@mcmaster.ca
                dmarsh@nosm.ca
                worster@mcmaster.ca
                dipika.desai@phri.ca
                thabanl@mcmaster.ca
                samaanz@mcmaster.ca
                Journal
                Syst Rev
                Syst Rev
                Systematic Reviews
                BioMed Central (London )
                2046-4053
                16 April 2015
                16 April 2015
                2015
                : 4
                : 49
                Affiliations
                [ ]Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S4L8 Canada
                [ ]Population Genomics Program, Chanchlani Research Centre, 1280 Main Street West, Hamilton, Ontario L8S4L8 Canada
                [ ]McMaster Integrative Neuroscience Discovery & Study (MiNDS) Program, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S4L8 Canada
                [ ]Department of Anesthesia, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S4L8 Canada
                [ ]Canadian Addiction Treatment Centres, 13291 Yonge St #403, Richmond, Hill, Ontario L4E4L6 Canada
                [ ]Northern Ontario School of Medicine, 935 Ramsey Lake Rd, Sudbury, Ontario P3E 2C6 Canada
                [ ]Department of Medicine, Hamilton General Hospital, 237 Barton St East, Hamilton, Ontario L8L 2X2 Canada
                [ ]Hamilton Health Sciences, Population Health Research Institute, 237 Barton St East, Hamilton, Ontario L8L 2X2 Canada
                [ ]Departments of Pediatrics and Anesthesia, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S4L8 Canada
                [ ]St. Joseph’s Healthcare Hamilton, Centre for Evaluation of Medicine, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6 Canada
                [ ]Biostatistics Unit, Father Sean O’Sullivan Research Centre, St. Joseph’s Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6 Canada
                [ ]Department of Psychiatry and Behavioral Neurosciences, McMaster University, 100 West 5th Street, Hamilton, Ontario L8N 3K7 Canada
                [ ]Peter Boris Centre for Addictions Research, 100 West 5th Street, Hamilton, Ontario L8N 3K7 Canada
                Article
                42
                10.1186/s13643-015-0042-2
                4403999
                25927914
                f721e0ec-b09a-4bd6-8908-53ff68d69dc6
                © Dennis et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 January 2015
                : 2 April 2015
                Categories
                Protocol
                Custom metadata
                © The Author(s) 2015

                Public health
                chronic pain,opioid maintenance,addiction,opioid substitution therapies,opioid dependence,buprenorphine/naloxone,methadone,methadone maintenance therapy,naltrexone,systematic review,network meta-analysis

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