Mattick, RP; Kimber, J; Breen, C; Davoli, M (2003) Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev, 2 (2).

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Background Buprenorphine has been reported as an alternative to methadone and LAAM for maintenance treatment of opioid dependence, differing results are reported concerning its relative effectiveness indicating the need for an integrative review. Objectives To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use. Search strategy We searched the following databases up to 2001, inclusive: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, 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), Library of Congress databases, available NIDA monographs, the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews. Authors of identified RCT's were asked about any other published or unpublished relevant RCT. Selection criteria Randomised clinical trials of buprenorphine maintenance versus either placebo or methadone maintenance for opioid dependence. Data collection and analysis Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation; data were extracted independently for meta-analysis and double-entered. Main results Thirteen studies met the inclusion criteria, all were randomised clinical trials, all but one were double-blind. The method of concealment of allocation was not clearly described in 11 of the studies, otherwise methodological quality was good. Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI: 0.69-0.96).

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Illustrative comparative risks* (95% CI) Outcomes Assumed risk Corresponding risk Relative effect (95% CI) No of Participants (studies) Quality of the evidence (GRADE) Comments No methadone maintenance treatment Methadone maintenance treatment Medium risk population Retention in treatment-Old studies (pre 2000) objective 210 per 1000 640 per 1000 (368 to 1123) RR 3.05 (1.75 to 5.35) 505 (3) ⊕⊕⊕⊕ high 1,2 Medium risk population Retention in treatment-New studies 154 per 1000 684 per 1000 (502 to 930) RR 4.44 (3.26 to 6.04) 750 (4) ⊕⊕⊕⊕ high 2,3 Medium risk population Morphine positive urine or hair analysis objective 701 per 1000 463 per 1000 (393 to 547) RR 0.66 (0.56 to 0.78) 1129 (6) ⊕⊕⊕⊕ high Medium risk population Criminal activity objective 118 per 1000 46 per 1000 (14 to 148) RR 0.39 (0.12 to 1.25) 363 (3) ⊕⊕⊕⊝ moderate 4 Medium risk population Mortality objective 17 per 1000 8 per 1000 RR 0.48 (0.1 to 2.39) 576 (4)

Background Methadone maintenance was the first widely used form of opioid replacement therapy developed 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. Objectives 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. Search strategy We searched all the following databases up to 2001: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, 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. Selection criteria All randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other nonpharmacological therapy for the treatment of opioid dependence. Data collection and analysis Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation, data were extracted independently for meta-analysis and double-entered.

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Background: Few European studies have investigated the effects of long-term exposure to both fine particulate matter (≤ 2.5 µm; PM2.5) and nitrogen dioxide (NO2) on mortality.Objectives: We studied the association of exposure to NO2, PM2.5, and traffic indicators on cause-specific mortality to evaluate the form of the concentration–response relationship.Methods: We analyzed a population-based cohort enrolled at the 2001 Italian census with 9 years of follow-up. We selected all 1,265,058 subjects ≥ 30 years of age who had been living in Rome for at least 5 years at baseline. Residential exposures included annual NO2 (from a land use regression model) and annual PM2.5 (from a Eulerian dispersion model), as well as distance to roads with > 10,000 vehicles/day and traffic intensity. We used Cox regression models to estimate associations with cause-specific mortality adjusted for individual (sex, age, place of birth, residential history, marital status, education, occupation) and area (socioeconomic status, clustering) characteristics.Results: Long-term exposures to both NO2 and PM2.5 were associated with an increase in nonaccidental mortality [hazard ratio (HR) = 1.03 (95% CI: 1.02, 1.03) per 10-µg/m3 NO2; HR = 1.04 (95% CI: 1.03, 1.05) per 10-µg/m3 PM2.5]. The strongest association was found for ischemic heart diseases (IHD) [HR = 1.10 (95% CI: 1.06, 1.13) per 10-µg/m3 PM2.5], followed by cardiovascular diseases and lung cancer. The only association showing some deviation from linearity was that between NO2 and IHD. In a bi-pollutant model, the estimated effect of NO2 on mortality was independent of PM2.5.Conclusions: This large study strongly supports an effect of long-term exposure to NO2 and PM2.5 on mortality, especially from cardiovascular causes. The results are relevant for the next European policy decisions regarding air quality.