Buprenorphine versus methadone for the treatment of opioid dependence: a systematic review and meta-analysis of randomised and observational studies.

BACKGROUND: Opioid dependence is associated with substantial health and social burdens, and opioid agonist treatment (OAT) is highly effective in improving multiple outcomes for people who receive this treatment. Methadone and buprenorphine are common medications provided as OAT. We aimed to examine buprenorphine compared with methadone in the treatment of opioid dependence across a wide range of primary and secondary outcomes. METHODS: We did a systematic review and meta-analysis in accordance with GATHER and PRISMA guidelines. We searched Embase, MEDLINE, CENTRAL, and PsycINFO from database inception to Aug 1, 2022; clinical trial registries and previous relevant Cochrane reviews were also reviewed. We included all RCTs and observational studies of adults (aged ≥18 years) with opioid dependence comparing treatment with buprenorphine or methadone. Primary outcomes were retention in treatment at 1, 3, 6, 12, and 24 months, treatment adherence (measured through doses taken as prescribed, dosing visits attended, and biological measures), or extra-medical opioid use (measured by urinalysis and self-report). Secondary outcomes were use of benzodiazepines, cannabis, cocaine, amphetamines, and alcohol; withdrawal; craving; criminal activity and engagement with the criminal justice system; overdose; mental and physical health; sleep; pain; global functioning; suicidality and self-harm; and adverse events. Single-arm cohort studies and RCTs that collected data on buprenorphine retention alone were also reviewed. Data on study, participant, and treatment characteristics were extracted. Study authors were contacted to obtain additional data when required. Comparative estimates were pooled with use of random-effects meta-analyses. The proportion of individuals retained in treatment across multiple timepoints was pooled for each drug. This study is registered with PROSPERO (CRD42020205109). FINDINGS: We identified 32 eligible RCTs (N=5808 participants) and 69 observational studies (N=323 340) comparing buprenorphine and methadone, in addition to 51 RCTs (N=11 644) and 124 observational studies (N=700 035) that reported on treatment retention with buprenorphine. Overall, 61 studies were done in western Europe, 162 in North America, 14 in north Africa and the Middle East, 20 in Australasia, five in southeast Asia, seven in south Asia, two in eastern Europe, three in central Europe, one in east Asia, and one in central Asia. 1 040 827 participants were included in these primary studies; however, gender was only reported for 572 111 participants, of whom 377 991 (66·1%) were male and 194 120 (33·9%) were female. Mean age was 37·1 years (SD 6·0). At timepoints beyond 1 month, retention was better for methadone than for buprenorphine: for example, at 6 months, the pooled effect favoured methadone in RCTs (risk ratio 0·76 [95% CI 0·67-0·85]; I·=74·2%; 16 studies, N=3151) and in observational studies (0·77 [0·68-0·86]; I·=98·5%; 21 studies, N=155 111). Retention was generally higher in RCTs than observational studies. There was no evidence suggesting that adherence to treatment differed with buprenorphine compared with methadone. There was some evidence that extra-medical opioid use was lower in those receiving buprenorphine in RCTs that measured this outcome by urinalysis and reported proportion of positive urine samples (over various time frames; standardised mean difference -0·20 [-0·29 to -0·11]; I·=0·0%; three studies, N=841), but no differences were found when using other measures. Some statistically significant differences were found between buprenorphine and methadone among secondary outcomes. There was evidence of reduced cocaine use, cravings, anxiety, and cardiac dysfunction, as well as increased treatment satisfaction among people receiving buprenorphine compared with methadone; and evidence of reduced hospitalisation and alcohol use in people receiving methadone. These differences in secondary outcomes were based on small numbers of studies (maximum five), and were often not consistent across study types or different measures of the same constructs (eg, cocaine use). INTERPRETATION: Evidence from trials and observational studies suggest that treatment retention is better for methadone than for sublingual buprenorphine. Comparative evidence on other outcomes examined showed few statistically significant differences and was generally based on small numbers of studies. These findings highlight the imperative for interventions to improve retention, consideration of client-centred factors (such as client preference) when selecting between methadone and buprenorphine, and harmonisation of data collection and reporting to strengthen future syntheses. FUNDING: Australian National Health and Medical Research Council.

Mortality among people who inject drugs: Ten-year follow-up of the hepatitis C virus cohort.

INTRODUCTION AND AIMS: Mortality studies of people who inject drugs (PWID) are mostly of older people and drug treatment cohorts. We estimate mortality rates, describe causes of death, and years of potential life lost in a community-recruited cohort of young PWID characterised by high incidence of hepatitis C virus (HCV) infection. DESIGN AND METHODS: Participant identifiers of 215 PWID from the south-western Sydney sub-cohort of the HCV Cohort were linked to National Death Index records from 1999 to 2010 and crude mortality rates and standardised mortality ratios estimated. Australian life tables were used to calculate years of potential of life lost. RESULTS: Fifteen participants died (7.0%) in 2095 person years (PY) of follow-up. Median age at death was 30.6 years (interquartile range 24.9-32.2). The crude mortality rate was 0.72 per 100PY (95% confidence interval 0.29-0.79) with a standardised mortality ratio of 11.09 (95% confidence interval 6.68-18.39). One-third of deaths were due to accidental drug overdose (5/15) and one-fifth were suicides (3/15). All deaths from defined causes (13/15) were potentially avoidable. Decedents lost on average 49.8 years of potential life. DISCUSSION AND CONCLUSIONS: Mortality and potential life lost further highlight the impact of accidental overdose deaths and suicide among young PWID. Integration of overdose and suicide prevention into youth-orientated outreach, including innovation in online and mobile technology should be evaluated.

Estimating the number of people who inject drugs in Australia.

BACKGROUND: Injecting drug use is associated with considerable morbidity and mortality. Estimates of the size of the population of people who inject drugs are critical to inform service planning and estimate disease burden due to injecting drug use. We aimed to estimate the size of the population of people who inject drugs in Australia. METHODS: We applied a multiplier method which used benchmark data (number of people in opioid substitution therapy (OST) on a snapshot day in 2014) and multiplied it by a factor derived from the prevalence of current OST among people who inject drugs participating in the Australian Needle and Syringe Program Survey in 2014. Estimates of the total population of people who inject drugs were calculated in each state and territory and summed to produce a national estimate. We used the sex and age group distribution seen in datasets relating to people who inject drugs to derive sex- and age-stratified estimates, and calculated prevalence per 1000 population. RESULTS: Between 68,000 and 118,000 people aged 15-64 years inject drugs in Australia. The population prevalence of injecting drug use was 6.0 (lower and upper uncertainty intervals of 4.3 and 7.6) per 1000 people aged 15-64 years. Injecting drug use was more common among men than women, and most common among those aged 35-44 years. Comparison of expected drug-related deaths based on these estimates to actual deaths suggest that these figures may be underestimates. CONCLUSIONS: These are the first indirect prevalence estimates of injecting drug use in Australia in over a decade. This work has identified that there are limited data available to inform estimates of this population. These estimates can be used as a basis for further work estimating injecting drug use in Australia.

Mortality risk of opioid substitution therapy with methadone versus buprenorphine: a retrospective cohort study.

BACKGROUND: Opioid dependence increases risk of premature mortality. Opioid substitution therapy with methadone or buprenorphine reduces mortality risk, especially for drug-related overdose. Clinical guidelines recommend methadone as the first line of opioid substitution therapy. We aimed to test whether buprenorphine treatment has a lower mortality risk than does methadone treatment by comparing all-cause mortality and drug-related overdose mortality at treatment induction, after in-treatment medication switches, and following treatment cessation. METHODS: We did a retrospective cohort study of all patients with opioid dependency (n=32,033) in New South Wales, Australia, who started a methadone or buprenorphine treatment episode from Aug 1, 2001, to Dec 31, 2010, including 190,232·6 person-years of follow-up. We compared crude mortality rates (CMRs) for all-cause and drug-related overdose mortality, and mortality rate ratios (MRRs) according to age, sex, period in or out of treatment, medication type, and in-treatment switching. FINDINGS: Patients who initiated with buprenorphine had reduced all-cause and drug-related mortality during the first 4 weeks of treatment compared with those who initiated with methadone (adjusted all-cause MRR 2·17, 95% CI 1·29-3·67; adjusted drug-related MRR 4·88, 1·73-13·69). For the remaining time on treatment, drug-related mortality risk did not differ (adjusted MRR 1·18, 95% CI 0·89-1·56), but weak evidence suggested that all-cause mortality was lower for buprenorphine than methadone (1·66, 1·40-1·96). In the 4 weeks after treatment cessation, all-cause mortality did not differ, but drug-related mortality was lower for methadone (adjusted all-cause MRR 1·12, 0·79-1·59; adjusted drug-related MRR 0·50, 0·29-0·86). Patients who switched from buprenorphine to methadone during treatment had lower mortality in the first 4 weeks of methadone treatment than matched controls who received methadone only (CMR difference 7·1 per 1000 person-years, 95% CI 0·1-14·0); no mortality difference was noted for switches from buprenorphine to methadone or for switches to either medication beyond the first 4 weeks of treatment. INTERPRETATION: In a setting with high risk of death in the first 4 weeks of opioid substitution therapy, buprenorphine seemed to reduce mortality in this period, but little difference between buprenorphine and methadone was noted thereafter or for in-treatment switching of medications. Cross-cohort corroboration of our findings and further assessment of the stepped treatment model is warranted. FUNDING: Australian National Health & Medical Research Council.

Excess mortality among opioid-using patients treated with oral naltrexone in Australia.

INTRODUCTION AND AIMS: To estimate the number of deaths that would have occurred among patients receiving oral naltrexone for opioid use under the Special Access Scheme if these patients had received methadone. DESIGN AND METHODS: We analysed mortality in cohorts treated with oral naltrexone and methadone. Data were from 1097 patients of in WA providing oral naltrexone for opioid use under the SAS,1998-2000, and all participants in WA (n = 2520) and New South Wales (NSW) (n = 11,174) methadone programs over the same period. We calculated mortality rates among patients receiving naltrexone and methadone, and excess mortality among patients receiving naltrexone. RESULTS: Oral naltrexone patients had higher mortality than those treated with methadone, even when favourable assumptions were made about the effects of naltrexone on mortality. Total oral naltrexone mortality was significantly greater than for methadone in WA (rate ratio 3.5; 95% confidence interval 2.2-5.8) and NSW (rate ratio 3.5; 95% confidence interval 2.4-5.0). Among 1097 oral naltrexone patients we estimate that there were 25-29 deaths over two years that would probably not have occurred if these patients had received methadone. The major reason was higher mortality rate post-treatment cessation. DISCUSSION AND CONCLUSIONS: Large-scale use of oral naltrexone to treat opioid users may not have, as intended, saved lives. Implant naltrexone continues to be prescribed under the SAS in the absence of reliable efficacy and safety data. There is a need to review widespread use of unregistered medications under the SAS, particularly with vulnerable patient groups.

A longitudinal comparison of retention in buprenorphine and methadone treatment for opioid dependence in New South Wales, Australia.

BACKGROUND AND AIMS: To examine characteristics of first-time methadone and buprenorphine clients and factors associated with risk of leaving first treatment in New South Wales (NSW), Australia. DESIGN: Retrospective linkage study of opioid substitution therapy (OST) treatment, court, custody and mortality data. SETTING: NSW, Australia. PARTICIPANTS: First-time OST entrants (August 2001-December 2010). MEASUREMENTS: Characteristics of clients were examined. Time-dependent Cox models examined factors associated with the risk of leaving first treatment, with demographic, criminographic and treatment variables jointly considered. Interactions between medication and other variables upon risk of leaving treatment were examined. FINDINGS: There were 15 600 treatment entrants: 7183 (46%) commenced buprenorphine, 8417 (54%) commenced methadone; the proportion entering buprenorphine increased over time. Those starting buprenorphine switched medications more frequently and had more subsequent treatment episodes. Buprenorphine retention was also poorer. On average, 44% spent 3+ months in treatment compared with 70% of those commencing methadone; however, buprenorphine retention for first-time entrants improved over time, whereas methadone retention did not. Multivariable Cox models indicated that in addition to sex, age, treatment setting and criminographic variables, the risk of leaving a first treatment episode was greater on any given day for those receiving buprenorphine, and was dependent on the year treatment was initiated. There was no interaction between any demographic variables and medication received, suggesting no clear evidence of any particular groups for whom each medication might be better suited in terms of improving retention. CONCLUSIONS: Although retention rates for buprenorphine treatment have improved in New South Wales, Australia, individuals starting methadone treatment still show higher retention rates.

Offending, custody and opioid substitution therapy treatment utilisation among opioid-dependent people in contact with the criminal justice system: comparison of Indigenous and non-Indigenous Australians.

BACKGROUND: Although Indigenous Australians are over-represented among heroin users, there has been no study examining offending, time in custody, and opioid substitution therapy (OST) treatment utilisation among Indigenous opioid-dependent (including heroin) people at the population level, nor comparing these to non-Indigenous opioid-dependent people. The aims of this study were to compare the nature and types of charges, time in custody and OST treatment utilisation between opioid-dependent Indigenous and non-Indigenous Australians in contact with the criminal justice system. METHODS: This was a population-based, retrospective data linkage study using records of OST entrants in New South Wales, Australia (1985-2010), court appearances (1993-2011) and custody episodes (2000-2012). Charge rates per 100 person-years were compared between Indigenous and non-Indigenous Australians by sex, age and calendar year. Statistical comparisons were made for variables describing the cumulative time and percentage of follow-up time spent in custody, as well as characteristics of OST initiation and overall OST treatment utilisation. RESULTS: Of the 34,962 people in the cohort, 6,830 (19.5%) were Indigenous and 28,132 (80.5%) non-Indigenous. Among the 6,830 Indigenous people, 4,615 (67.6%) were male and 2,215 (32.4%) female. The median number of charges per person against Indigenous people (25, IQR 31) was significantly greater than non-Indigenous people (9, IQR 16) (p < 0.001). Overall, Indigenous people were charged with 33.2% of the total number of charges against the cohort and 44.0% of all violent offences. The median percentage of follow-up time that Indigenous males and females spent in custody was twice that of non-Indigenous males (21.7% vs. 10.1%, p < 0.001) and females (6.0% vs. 2.9%, p < 0.001). The percentage of Indigenous people who first commenced OST in prison (30.2%) was three times that of non-Indigenous people (11.2%) (p < 0.001). Indigenous males spent less time in OST compared to non-Indigenous males (median percentage of follow-up time in treatment: 40.5% vs. 43.1%, p < 0.001). CONCLUSIONS: Compared to non-Indigenous opioid-dependent people, Indigenous opioid-dependent people in contact with the criminal justice system are charged with a greater number of offences, spend longer in custody and commonly initiate OST in prison. Hence, contact with the criminal justice system provides an important opportunity to engage Indigenous people in OST.

A comparative study of opioid substitution therapy utilisation among opioid-dependent men and women.

INTRODUCTION AND AIMS: Few population-based studies have examined differences in opioid substitution therapy (OST) treatment utilisation between men and women. Using a population of opioid-dependent people in New South Wales, Australia, first-episode and long-term OST treatment utilisation profiles were compared between men and women, differentiating between treatment initiation in the community and in custody. DESIGN AND METHODS: Retrospective data linkage study using records of new OST entrants (2001-2010) and custody episodes (2000-2012). First OST treatment episode and overall treatment utilisation characteristics were compared between men and women initiating treatment in the community or in custody. Treatment retention was evaluated at 3, 6, 9 and 12 months after first commencing OST and overall, as the median proportion of follow-up time spent in treatment. RESULTS: There were 15,600 new OST entrants in the cohort--10,930 were men (70.1%) and 4670 women (29.9%); 12,584 (80.7%) initiated treatment in the community and 3016 (19.3%) in custody. More men initiated OST in custody (24.0% vs. 8.3%, P < 0.001) and only received OST in custody (57.5% vs. 41.8%, P < 0.001). Women were retained longer in their first OST treatment episode at all four time points in both treatment settings and in treatment overall (community: 46.6% vs. 39.1%, P < 0.001; custody: 41.3% vs. 30.8%, P < 0.001). DISCUSSION AND CONCLUSIONS: There are a number of key differences in OST treatment utilisation profiles between men and women. Whereas men commonly initiate and only receive OST in custody, treatment retention is higher among women, independent of the setting treatment is initiated.

Opioid substitution therapy as a strategy to reduce deaths in prison: retrospective cohort study.

OBJECTIVES: To describe deaths in prison among opioid-dependent people, and examine associations between receipt of opioid substitution therapy (OST) and risk of death in prison. DESIGN: Retrospective cohort study. SETTING: Adult prisons in New South Wales (NSW), Australia. PARTICIPANTS: 16 715 opioid-dependent people who were received to prison between 2000 and 2012. INTERVENTIONS: Opioid substitution therapy. PRIMARY OUTCOME MEASURES: Natural and unnatural (suicide, drug-induced, violent and other injury) deaths in prison. RESULTS: Cohort members were in prison for 30 998 person-years (PY), during which time there were 51 deaths. The all-cause crude mortality rate (CMR) in prison was 1.6/1000 PY (95% CI 1.2 to 2.2/1000 PY), and the unnatural death CMR was 1.1/1000 PY (95% CI 0.8 to 1.6/1000 PY). Compared to time out of OST, the hazard of all-cause death was 74% lower while in OST (adjusted HR (AHR): 0.26; 95% CI 0.13 to 0.50), and the hazard of unnatural death was 87% lower while in OST (AHR: 0.13; 95% CI 0.05 to 0.35). The all-cause and unnatural death CMRs during the first 4 weeks of incarceration were 6.6/1000 PY (95% CI 3.8 to 10.6/1000 PY) and 5.5/1000 PY (95% CI 2.9 to 9.4/1000 PY), respectively. Compared to periods not in OST, the hazard of all-cause death during the first 4 weeks of incarceration was 94% lower while in OST (AHR: 0.06; 95% CI 0.01 to 0.48), and the hazard of unnatural death was 93% lower while in OST (AHR: 0.07; 95% CI 0.01 to 0.53). CONCLUSIONS: Mortality of opioid-dependent prisoners was significantly lower while in receipt of OST.

The impact of opioid substitution therapy on mortality post-release from prison: retrospective data linkage study.

AIMS: Release from prison is a high-risk period for mortality. We examined the impact of opioid substitution therapy (OST), for opioid dependence during and after incarceration, upon mortality post-release. DESIGN: A cohort was formed of all opioid-dependent people who entered OST between 1985 and 2010 and who, following first OST entry, were released from prison at least once between 2000 and 2012. We linked data on OST history, court and prison records and deaths. SETTING: New South Wales (NSW), Australia. PARTICIPANTS: A total of 16,453 people released from prison 60,161 times. MEASUREMENTS: Crude mortality rates (CMRs) were calculated according to OST retention; multivariable Cox regressions for post-release periods were undertaken to examine the association between OST exposure (a time-dependent variable) and mortality post-release, for which covariates were updated per-release. FINDINGS: There were 100,978 person-years (PY) post-release; 1050 deaths occurred. Most received OST while incarcerated (76.5%); individuals were receiving OST in 51% of releases. Lowest post-release mortality was among those continuously retained in OST post-release CMR 4 weeks post-release = 6.4 per 1000 PY; 95% confidence interval (CI) = 5.2, 7.8, highest among those with no OST (CMR = 36.7 per 1000 PY; 95% CI = 28.8, 45.9). Multi-factorial models showed OST exposure in the 4 weeks post-release reduced hazard of death by 75% (adjusted hazard ratio 0.25; 95% CI = 0.12, 0.53); OST receipt in prison had a short-term protective effect that decayed quickly across time. CONCLUSION: In New South Wales, Australia, opioid substitution therapy in prison and post-release appears to reduce mortality risk in the immediate post-release period.

Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence.

BACKGROUND: Buprenorphine maintenance treatment has been evaluated in randomised controlled trials against placebo medication, and separately as an alternative to methadone for management of opioid dependence. OBJECTIVES: To evaluate buprenorphine maintenance compared to placebo and to methadone maintenance in the management of opioid dependence, including its ability to retain people in treatment, suppress illicit drug use, reduce criminal activity, and mortality. SEARCH METHODS: We searched the following databases to January 2013: Cochrane Drugs and Alcohol Review Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Current Contents, PsycLIT, CORK, Alcohol and Drug Council of Australia, Australian Drug Foundation, Centre for Education and Information on Drugs and Alcohol, Library of Congress, reference lists of identified studies and reviews. We sought published/unpublished randomised controlled trials (RCTs) from authors. SELECTION CRITERIA: Randomised controlled trials of buprenorphine maintenance treatment versus placebo or methadone in management of opioid-dependent persons. DATA COLLECTION AND ANALYSIS: We used Cochrane Collaboration methodology. MAIN RESULTS: We include 31 trials (5430 participants), the quality of evidence varied from high to moderate quality.There is high quality of evidence that buprenorphine was superior to placebo medication in retention of participants in treatment at all doses examined. Specifically, buprenorphine retained participants better than placebo: at low doses (2 - 6 mg), 5 studies, 1131 participants, risk ratio (RR) 1.50; 95% confidence interval (CI) 1.19 to 1.88; at medium doses (7 - 15 mg), 4 studies, 887 participants, RR 1.74; 95% CI 1.06 to 2.87; and at high doses (≥ 16 mg), 5 studies, 1001 participants, RR 1.82; 95% CI 1.15 to 2.90. However, there is moderate quality of evidence that only high-dose buprenorphine (≥ 16 mg) was more effective than placebo in suppressing illicit opioid use measured by urinanalysis in the trials, 3 studies, 729 participants, standardised mean difference (SMD) -1.17; 95% CI -1.85 to -0.49, Notably, low-dose, (2 studies, 487 participants, SMD 0.10; 95% CI -0.80 to 1.01), and medium-dose, (2 studies, 463 participants, SMD -0.08; 95% CI -0.78 to 0.62) buprenorphine did not suppress illicit opioid use measured by urinanalysis better than placebo.There is high quality of evidence that buprenorphine in flexible doses adjusted to participant need,was less effective than methadone in retaining participants, 5 studies, 788 participants, RR 0.83; 95% CI 0.72 to 0.95. For those retained in treatment, no difference was observed in suppression of opioid use as measured by urinalysis, 8 studies, 1027 participants, SMD -0.11; 95% CI -0.23 to 0.02 or self report, 4 studies, 501 participants, SMD -0.11; 95% CI -0.28 to 0.07, with moderate quality of evidence.Consistent with the results in the flexible-dose studies, in low fixed-dose studies, methadone (≤ 40 mg) was more likely to retain participants than low-dose buprenorphine (2 - 6 mg), (3 studies, 253 participants, RR 0.67; 95% CI: 0.52 to 0.87). However, we found contrary results at medium dose and high dose: there was no difference between medium-dose buprenorphine (7 - 15 mg) and medium-dose methadone (40 - 85 mg) in retention, (7 studies, 780 participants, RR 0.87; 95% CI 0.69 to 1.10) or in suppression of illicit opioid use as measured by urines, (4 studies, 476 participants, SMD 0.25; 95% CI -0.08 to 0.58) or self report of illicit opioid use, (2 studies, 174 participants, SMD -0.82; 95% CI -1.83 to 0.19). Similarly, there was no difference between high-dose buprenorphine (≥ 16 mg) and high-dose methadone (≥ 85 mg) in retention (RR 0.79; 95% CI 0.20 to 3.16) or suppression of self-reported heroin use (SMD -0.73; 95% CI -1.08 to -0.37) (1 study, 134 participants).Few studies reported adverse events ; two studies compared adverse events statistically, finding no difference between methadone and buprenorphine, except for a single result indicating more sedation among those using methadone. AUTHORS' CONCLUSIONS: Buprenorphine is an effective medication in the maintenance treatment of heroin dependence, retaining people in treatment at any dose above 2 mg, and suppressing illicit opioid use (at doses 16 mg or greater) based on placebo-controlled trials.However, compared to methadone, buprenorphine retains fewer people when doses are flexibly delivered and at low fixed doses. If fixed medium or high doses are used, buprenorphine and methadone appear no different in effectiveness (retention in treatment and suppression of illicit opioid use); however, fixed doses are rarely used in clinical practice so the flexible dose results are more relevant to patient care. Methadone is superior to buprenorphine in retaining people in treatment, and methadone equally suppresses illicit opioid use.

Interventions to prevent HIV and Hepatitis C in people who inject drugs: a review of reviews to assess evidence of effectiveness.

BACKGROUND: Injecting drug use is a major risk factor for the acquisition and transmission of HIV and Hepatitis C virus (HCV). Prevention of these infections among people who inject drugs (PWID) is critical to reduce ongoing transmission, morbidity and mortality. METHODS: A review of reviews was undertaken involving systematic literature searches of Medline, Embase, CINAHL, PsychINFO, IBSS and the Cochrane Library (2000-2011) to identify English language reviews regarding the effectiveness of harm reduction interventions in relation to HIV transmission, HCV transmission and injecting risk behaviour (IRB). Interventions included needle and syringe programmes (NSP); the provision of injection paraphernalia; opiate substitution treatment (OST); information, education and counselling (IEC); and supervised injecting facilities (SIFs). Reviews were classified into 'core' or 'supplementary' using critical appraisal criteria, and the strength of review-level evidence was assessed. RESULTS: Twelve core and thirteen supplementary reviews were included. From these reviews we identified: (i) for NSP: tentative review-level evidence to support effectiveness in reducing HIV transmission, insufficient review-level evidence relating to HCV transmission, but sufficient review-level evidence in relation to IRB; (ii) for OST: sufficient review-level evidence of effectiveness in relation to HIV transmission and IRB, but tentative review-level evidence in relation to HCV transmission; (iii) for IEC, the provision of injection paraphernalia and SIFs: tentative review-level evidence of effectiveness in reducing IRB; and either insufficient or no review-level evidence for these interventions in relation to HIV or HCV transmission. CONCLUSION: Review-level evidence indicates that harm reduction interventions can reduce IRB, with evidence strongest for OST and NSP. However, there is comparatively little review-level evidence regarding the effectiveness of these interventions in preventing HCV transmission among PWID. Further studies are needed to assess the effectiveness and impact of scaling up comprehensive packages of harm reduction interventions to minimise HIV and HCV transmission among PWID.

Imprisonment of opioid-dependent people in New South Wales, Australia, 2000­2012: a retrospective linkage study.

There are few data about the incarceration of opioid-dependent people involving large representative cohorts. We aimed to determine the prevalence and duration of incarceration in a large cohort of opioid-dependent people in Australia using data linkage methods, and estimate the costs associated with their incarceration.Method: Retrospective linkage study of all entrants to opioid substitution therapy (OST) for the treatment of opioid dependence in NSW, 1985­2010, with data on incarceration, 2000-2012. The number and duration of incarcerations were calculated. The average daily cost of incarceration was applied to days of incarceration in the cohort.Results: Among 47,196 opioid-dependent people, 37% (43% of men and 24% of women) had at least one episode of incarceration lasting one or more days. Men had a median of three(ranging between 1-47) incarcerations, and women, two (1-35). Indigenous men spent 23% of follow-up time incarcerated, compared with 8% for non-Indigenous men; similarly, Indigenous women spent a substantially greater proportion of time incarcerated than non-Indigenous women (8% vs. 2%). Costs of incarceration of this cohort between 2000 and 2012 totalled nearly AUD $3 billion.Conclusions: This is the first study to examine incarceration of opioid-dependent people across an entire population of such users. Our findings suggest that a substantial minority of opioid-dependent people experience incarceration, usually on multiple occasions and at significant cost. Treatment for opioid dependence, inside and outside prisons, may help reduce incarceration of this cohort.

Engagement with the criminal justice system among opioid-dependent people: a retrospective cohort study.

AIMS: Studies of offending among people who use drugs typically focus upon small and potentially unrepresentative samples. We examined an entire population of opioid-dependent clients' contact with the criminal justice system to develop more accurate population-wide measures of offending among opioid-dependent people in Australia. DESIGN: Retrospective data linkage study. SETTING: All entrants to opioid substitution therapy (OST) for opioid dependence in New South Wales, Australia, between 1985 and 2010, with data on court appearances from 1 December 1993 to 31 March 2011. PARTICIPANTS: All 48 069 valid cohort members who received OST between 1985 and 2010. MEASUREMENTS: Person-years (PY) of observation and charge rates for major crime categories estimated by sex, age and time. FINDINGS: A total of 638 545 charges were laid against cohort members between 1993 and 2011. Eight in 10 males (79.7%) and 67.9% of females had at least one charge; rates were 94.15 per 100 PY [95% confidence interval (CI) = 93.89-94.41] among males, and 53.19 per 100 PY (95% CI = 52.91-53.46) among females, and highest at 15-19 years [175.74/100 PY males (95% CI = 174.45-177.03), 75.60/100 PY females (95% CI = 74.46-76.76)] and 20-24 years [144.61/100 PY males (95% CI = 143.70-145.53), 84.50/100 PY females (95% CI = 83.53-85.48)]. The most frequent charges were theft (24.5% of charges), traffic/vehicle (16.3%), offences against justice (10.5%), illicit drug (10.0%), intentional injury (9.9%) and public order offences (8.9%). Overall, 20.8% of the cohort accounted for 67.4% of charges. The most frequently appearing 5.6% of the cohort accounted for 24.3% of costs ($75.5 million). CONCLUSIONS: Among opioid-dependent people in Australia, a minority account for the majority of the criminal justice contact and levels of offending are not consistent over time, sex or age.

Early life influences on the risk of injecting drug use: case control study based on the Edinburgh Addiction Cohort.

AIMS: To investigate childhood influences on onset of injection drug use. DESIGN: Matched case-control study. SETTING: Edinburgh, Scotland. PARTICIPANTS: A total of 432 individuals presenting at a community health facility with injection drug use and 432 age- and sex-matched non-injecting controls recruited through the same facility. MEASUREMENTS: Main exposures considered were family structure and experience of public care, carer substance use, physical and sexual victimization and conduct problems, all measured at personal interview. The outcome was history of adult injection drug use recorded in medical records corroborated at personal interview. FINDINGS: Compared to two-parent families all other family structures were associated with increased risk of injection drug use, the greatest increased risk being associated with public care. Violence, criminality and financial problems in the family were also associated with increased risk, as were all types of carer substance use. The greatest increased risk was associated with markers of early conduct problems, particularly school exclusion and childhood contact with the criminal justice system. In multivariable analyses the strongest risk factors for later injecting were always having lived with a relative or family friend (not always a parent) and in care/adopted/foster home at any point [odds ratio (OR) = 2.66, 95% confidence interval (CI): 1.02-6.92 and OR = 2.17, 95% CI: 0.91-5.17, respectively], experienced violence from parent or carer (OR = 2.06, 95% CI: 1.26, 3.38) and early evidence of conduct problems [ever excluded from school (OR = 2.73, 95% CI: 1.68, 4.45); childhood criminality (ever arrested by police pre-adult OR = 3.05, 95% CI: 1.90, 4.89, ever been in borstal/young offenders/list D school OR = 4.70, 95% CI: 2.02, 10.94)]. After adjustment for family structure and conduct problems, sexual victimization was associated weakly with injecting onset (OR = 1.29, 95% CI: 0.76-2.19). More than 70% of injection drug use onset appeared attributable to the risk factors identified. CONCLUSIONS: Injection drug use in adults is associated strongly with prior childhood adversity, in particular not living with both parents and early conduct problems. Prevention initiatives should also consider these risk factors.

Survival and cessation in injecting drug users: prospective observational study of outcomes and effect of opiate substitution treatment.

OBJECTIVES: To examine survival and long term cessation of injecting in a cohort of drug users and to assess the influence of opiate substitution treatment on these outcomes. DESIGN: Prospective open cohort study. SETTING: A single primary care facility in Edinburgh. PARTICIPANTS: 794 patients with a history of injecting drug use presenting between 1980 and 2007; 655 (82%) were followed up by interview or linkage to primary care records and mortality register, or both, and contributed 10,390 person years at risk; 557 (85%) had received opiate substitution treatment. MAIN OUTCOME MEASURES: Duration of injecting: years from first injection to long term cessation, defined as last injection before period of five years of non-injecting; mortality before cessation; overall survival. RESULTS: In the entire cohort 277 participants achieved long term cessation of injecting, and 228 died. Half of the survivors had poor health related quality of life. Median duration from first injection to death was 24 years for participants with HIV and 41 years for those without HIV. For each additional year of opiate substitution treatment the hazard of death before long term cessation fell 13% (95% confidence interval 17% to 9%) after adjustment for HIV, sex, calendar period, age at first injection, and history of prison and overdose. Conversely exposure to opiate substitution treatment was inversely related to the chances of achieving long term cessation. CONCLUSIONS: Opiate substitution treatment in injecting drug users in primary care reduces this risk of mortality, with survival benefits increasing with cumulative exposure to treatment. Treatment does not reduce the overall duration of injecting.

Evidence for the effectiveness of sterile injecting equipment provision in preventing hepatitis C and human immunodeficiency virus transmission among injecting drug users: a review of reviews.

AIMS: To review the evidence on the effectiveness of harm reduction interventions involving the provision of sterile injecting equipment in the prevention of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs). The interventions assessed were needle and syringe programmes (NSP), alternative modes of needle/syringe provision (pharmacies, vending machines and outreach) and the provision of injecting equipment other than needles/syringes. METHODS: Systematic searches of the English language literature to March 2007 were undertaken to identify systematic, narrative or meta-analytical reviews (also known as a review of reviews) of the impact of interventions on HCV transmission, HIV transmission or injecting risk behaviour (IRB). Critical appraisal criteria classified the reviews as either high quality ('core') or supplementary: a framework based on the quality of reviews, the reviewers' conclusions and the designs/findings of the primary studies was used to derive evidence statements. RESULTS: Three core and two supplementary reviews of injecting equipment interventions were identified. According to the proposed framework, this study found (a) insufficient evidence to conclude that any of the interventions are effective in preventing HCV transmission; (b) tentative evidence to support the effectiveness of NSP in preventing HIV transmission; (c) sufficient evidence to support the effectiveness of NSP (and tentative evidence of an additional impact of pharmacy NSP) in reducing self-reported IRB; and (d) little to no evidence on vending machines, outreach or providing other injecting equipment in relation to any of the outcomes. CONCLUSIONS: The evidence is weaker than given credit for in the literature. The lack of evidence for effectiveness of NSP vis-à-vis biological outcomes (HCV and HIV incidence/prevalence) reflects the limitations of studies that have been undertaken to investigate these associations. Particularly for HCV, low levels of IRB may be insufficient to reduce high levels of transmission. New studies are required to identify the intervention coverage necessary to achieve sustained changes in blood-borne virus transmission.

The Edinburgh Addiction Cohort: recruitment and follow-up of a primary care based sample of injection drug users and non drug-injecting controls.

BACKGROUND: Injection drug use is an important public health problem. Epidemiological understanding of this problem is incomplete as longitudinal studies in the general population are difficult to undertake. In particular little is known about early life risk factors for later drug injection or about the life course of injection once established including the influence of medical and social interventions. METHODS: Individuals thought to be drug injectors were identified through a single primary medical care facility in Edinburgh between 1980 and 2006 and flagged with the General Registry Office. From October 2005 - October 2007, these cases were traced and invited to undergo interview assessment covering early life experience, substance use, health and social histories. Age and sex matched controls for confirmed cases (alive and dead) were later recruited through the same health facility. Controls for living cases completed the same structured interview schedule. Data were also collected on cases and controls through linkage to routine primary care records, death registrations, hospital contact statistics and police and prison records. All interviews were conducted with the knowledge and permission of the current GP. RESULTS: The initial cohort size was 814. At start of follow up 227 had died. Of the remaining 587: 20 had no contact details and 5 had embarked from the UK; 40 declined participation; 38 did not respond to invitations; 14 were excluded by their GP on health or social grounds and 22 had their contact details withheld by administrative authorities. 448 were interviewed of whom 16 denied injection and were excluded. Of 191 dead cases with medical records 4 were excluded as their records contained no evidence of injection. 5 interviewed cases died before follow up was concluded though these individuals were counted as "live" cases. 1 control per case (dead and alive) was recruited. Linkage to Scottish Morbidity Records data (available from 1981 onwards) on general acute inpatient and day cases, mental health inpatient and day cases and cancer was provided by Information Services, NHS Scotland, for all cases interviewed and all dead cases. The Scottish Prison Service provided records for 198 (46%) of cases interviewed, 48 cases not interviewed and 34 (18%) of dead cases. For a sub-sample of 100 interviewees a search of the Lothian and Borders police database was made for official criminal records and 94 had criminal records. Data linkage for controls is ongoing. CONCLUSIONS: Injecting drug users recruited from a community setting can be successfully followed-up through interviews and record linkage. Information from injecting cases is being analysed in terms of injecting patterns and possible influences on these. Comparisons between cases and controls will allow identification of possibly modifiable early life risk factors for drug injection and will also clarify the burden of disease associated with injection and the influence on this of different health and social interventions.