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      Retention of patients in opioid substitution treatment: A systematic review

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          Abstract

          Background

          Retention in opioid substitution (OST) treatment is associated with substantial reductions in all cause and overdose mortality. This systematic review aims to identify both protective factors supporting retention in OST, and risk factors for treatment dropout.

          Methods

          A systematic search was performed using MEDLINE, Embase, PsycInfo, CINAHL and Web of Science (January 2001 to October 2019). Randomised controlled trials (RCTs) and observational cohort studies reporting on retention rates and factors associated with retention in OST were included. Factors associated with treatment retention and dropout were explored according to the Maudsley Addiction Profile. A narrative synthesis is provided.

          Results

          67 studies were included in this review (4 RCTs and 63 observational cohort studies; N = 294,592), all assessing factors associated with retention in OST or treatment dropout. The median retention rate across observational studies was approximately 57% at 12 months, which fell to 38.4% at three years. Studies included were heterogeneous in nature with respect to treatment setting, type of OST, risk factor assessment, ascertainment of outcome and duration of follow-up. While the presence of such methodological heterogeneity makes it difficult to synthesise results, there is limited evidence to support the influence of a number of factors on retention, including age, substance use, OST drug dose, legal issues, and attitudes to OST.

          Conclusions

          Younger age, substance use particularly cocaine and heroin use, lower doses of methadone, criminal activity/incarceration, and negative attitudes to MMT appear to be associated with reduced retention in OST. A consensus definition of retention is required to allow for comparability across future studies.

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          Most cited references87

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          The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

          Summary Background Alcohol and drug use can have negative consequences on the health, economy, productivity, and social aspects of communities. We aimed to use data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 to calculate global and regional estimates of the prevalence of alcohol, amphetamine, cannabis, cocaine, and opioid dependence, and to estimate global disease burden attributable to alcohol and drug use between 1990 and 2016, and for 195 countries and territories within 21 regions, and within seven super-regions. We also aimed to examine the association between disease burden and Socio-demographic Index (SDI) quintiles. Methods We searched PubMed, EMBASE, and PsycINFO databases for original epidemiological studies on alcohol and drug use published between Jan 1, 1980, and Sept 7, 2016, with out language restrictions, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to estimate population-level prevalence of substance use disorders. We combined these estimates with disability weights to calculate years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 1990–2016. We also used a comparative assessment approach to estimate burden attributable to alcohol and drug use as risk factors for other health outcomes. Findings Globally, alcohol use disorders were the most prevalent of all substance use disorders, with 100·4 million estimated cases in 2016 (age-standardised prevalence 1320·8 cases per 100 000 people, 95% uncertainty interval [95% UI] 1181·2–1468·0). The most common drug use disorders were cannabis dependence (22·1 million cases; age-standardised prevalence 289·7 cases per 100 000 people, 95% UI 248·9–339·1) and opioid dependence (26·8 million cases; age-standardised prevalence 353·0 cases per 100 000 people, 309·9–405·9). Globally, in 2016, 99·2 million DALYs (95% UI 88·3–111·2) and 4·2% of all DALYs (3·7–4·6) were attributable to alcohol use, and 31·8 million DALYs (27·4–36·6) and 1·3% of all DALYs (1·2–1·5) were attributable to drug use as a risk factor. The burden of disease attributable to alcohol and drug use varied substantially across geographical locations, and much of this burden was due to the effect of substance use on other health outcomes. Contrasting patterns were observed for the association between total alcohol and drug-attributable burden and SDI: alcohol-attributable burden was highest in countries with a low SDI and middle-high middle SDI, whereas the burden due to drugs increased with higher S DI level. Interpretation Alcohol and drug use are important contributors to global disease burden. Effective interventions should be scaled up to prevent and reduce substance use disease burden. Funding Bill & Melinda Gates Foundation and Australian National Health and Medical Research Council.
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            Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence

            Cochrane Database of Systematic Reviews
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              Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence.

              Methadone maintenance was the first widely used opioid replacement therapy to treat heroin dependence, and it remains the best-researched treatment for this problem. Despite the widespread use of methadone in maintenance treatment for opioid dependence in many countries, it is a controversial treatment whose effectiveness has been disputed. To evaluate the effects of methadone maintenance treatment (MMT) compared with treatments that did not involve opioid replacement therapy (i.e., detoxification, offer of drug-free rehabilitation, placebo medication, wait-list controls) for opioid dependence. We searched the following databases up to Dec 2008: the Cochrane Controlled Trials Register, EMBASE, PubMED, CINAHL, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF-VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews; authors of identified RCTs were asked about other published or unpublished relevant RCTs. All randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other non-pharmacological therapy for the treatment of opioid dependence. Reviewers evaluated the papers separately and independently, rating methodological quality of sequence generation, concealment of allocation and bias. Data were extracted independently for meta-analysis and double-entered. Eleven studies met the criteria for inclusion in this review, all were randomised clinical trials, two were double-blind. There were a total number of 1969 participants. The sequence generation was inadequate in one study, adequate in five studies and unclear in the remaining studies. The allocation of concealment was adequate in three studies and unclear in the remaining studies. Methadone appeared statistically significantly more effective than non-pharmacological approaches in retaining patients in treatment and in the suppression of heroin use as measured by self report and urine/hair analysis (6 RCTs, RR = 0.66 95% CI 0.56-0.78), but not statistically different in criminal activity (3 RCTs, RR=0.39; 95%CI: 0.12-1.25) or mortality (4 RCTs, RR=0.48; 95%CI: 0.10-2.39). Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. It does not show a statistically significant superior effect on criminal activity or mortality.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: Project administrationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 May 2020
                2020
                : 15
                : 5
                : e0232086
                Affiliations
                [1 ] School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
                [2 ] Population Health Medicine, Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland
                [3 ] Data Science Centre, Royal College of Surgeons in Ireland, Dublin, Ireland
                Johns Hopkins University Bloomberg School of Public Health, UNITED STATES
                Author notes

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

                ‡ These authors are joint senior authors on this work.

                Author information
                http://orcid.org/0000-0002-1574-6732
                http://orcid.org/0000-0003-3228-0046
                Article
                PONE-D-19-20371
                10.1371/journal.pone.0232086
                7224511
                32407321
                3c397de7-4c97-4d3a-b52c-09c9d1b9e60a
                © 2020 O’Connor 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
                : 18 July 2019
                : 7 April 2020
                Page count
                Figures: 1, Tables: 3, Pages: 23
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100012921, Royal College of Surgeons in Ireland;
                Award ID: 2037E
                Award Recipient :
                Funded by: Health Research Board (Ireland)
                Award ID: HRA-PHR-2015-1088
                Award Recipient :
                This study was funded as part of author AMO’s PhD scholarship awarded by the Royal College of Surgeons in Ireland (RCSI) through their Strategic Academic Recruitment Programme (2037E). Authors LD and GC (PI) are funded by the Health Research Board (HRA-PHR-2015-1088). The funders had no role in the design and conduct of the study.
                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
                Pharmaceutics
                Drug Therapy
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Research and Analysis Methods
                Research Design
                Observational Studies
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Biology and Life Sciences
                Psychology
                Addiction
                Social Sciences
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                Addiction
                Physical Sciences
                Chemistry
                Chemical Compounds
                Alkaloids
                Cocaine
                Medicine and Health Sciences
                Pharmacology
                Behavioral Pharmacology
                Recreational Drug Use
                Cocaine
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                All relevant data are within the manuscript and its Supporting Information files.

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