IMPORTANCE Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality.OBJECTIVE To estimate the association of time receiving OAT with mortality.DATA SOURCES The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews.STUDY SELECTION All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included. DATA EXTRACTION AND SYNTHESISThis systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses. MAIN OUTCOMES AND MEASURESOverall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. RESULTSFifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI,, remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56). CONCLUSIONS AND RELEVANCEThis systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains ...

IMPORTANCE Extramedical opioid use has escalated in recent years. A better understanding of cause-specific mortality in this population is needed to inform comprehensive responses. OBJECTIVE To estimate all-cause and cause-specific crude mortality rates (CMRs) and standardized mortality ratios (SMRs) among people using extramedical opioids, including age-and sex-specific estimates when possible. DATA SOURCES For this systematic review and meta-analysis, MEDLINE, PsycINFO, and Embase were searched for studies published from January 1, 2009, to October 3, 2019, and an earlier systematic review on this topic published in 2011. STUDY SELECTION Cohort studies of people using extramedical opioids and reporting mortality outcomes were screened for inclusion independently by 2 team members. DATA EXTRACTION AND SYNTHESIS Data were extracted by a team member and checked by another team member. Study quality was assessed using a custom set of items that examined risk of bias and quality of reporting. Data were pooled using random-effects meta-analysis models. Heterogeneity was assessed using stratified meta-analyses and meta-regression. MAIN OUTCOMES AND MEASURES Outcome measures were all-cause and cause-specific CMRs and SMRs among people using extramedical opioids compared with the general population of the same age and sex. RESULTS Of 8683 identified studies, 124 were included in this analysis (100 primary studies and 24 studies providing additional data for primary studies). The pooled all-cause CMR, based on 99 cohorts of 1 262 592 people, was 1.6 per 100 person-years (95% CI, 1.4-1.8 per 100 person-years), with substantial heterogeneity (I 2 = 99.7%). Heterogeneity was associated with the proportion of the study sample that injected opioids or was living with HIV infection or hepatitis C. The pooled all-cause SMR, based on 43 cohorts, was 10.0 (95% CI, 7.6-13.2). Excess mortality was observed across a range of causes, including overdose, injuries, and infectious and noncommunicable diseases. CONCLUSIONS AND RELEVANCE The findings suggest that people using extramedical opioids experience significant excess mortality, much of which is preventable. The range of causes for which excess mortality was observed highlights the multiplicity of risk exposures experienced by this population and the need for comprehensive responses to address these. Better data on cause-specific mortality in this population in several world regions appear to be needed.

Aims To examine perceptions of extended‐release (XR) buprenorphine injections among people who regularly use opioids in Australia. Design Cross‐sectional survey prior to implementation. XR‐buprenorphine was registered in Australia in November 2018. Setting Sydney, Melbourne and Hobart. Participants A total of 402 people who regularly use opioids interviewed December 2017 to March 2018. Measurements Primary outcome concerned the proportion of participants who believed XR‐buprenorphine would be a good treatment option for them, preferred weekly versus monthly injections and perceived advantages/disadvantages of XR‐buprenorphine. Independent variables concerned the demographic characteristics and features of current opioid agonist treatment (OAT; medication‐type, dose, prescriber/dosing setting, unsupervised doses, out‐of‐pocket expenses and travel distance). Findings Sixty‐eight per cent [95% confidence interval (CI) = 63–73%] believed XR‐buprenorphine was a good treatment option for them. They were more likely to report being younger [26–35 versus > 55 years; odds ratio (OR) = 3.16, 95% CI = 1.12–8.89; P = 0.029], being female (OR = 1.67, 95% CI = 1.04–2.69; P = 0.034), < 10 years school education (OR = 1.87, 95% CI = 1.12–3.12; P = 0.016) and past‐month heroin (OR = 1.81, 95% CI = 1.15–2.85; P = 0.006) and methamphetamine use (OR = 1.90, 95% CI = 1.20–3.01; P = 0.006). Fifty‐four per cent reported no preference for weekly versus monthly injections, 7% preferred weekly and 39% preferred monthly. Among OAT recipients (n = 255), believing XR‐buprenorphine was a good treatment option was associated with shorter treatment episodes (1–2 versus ≥ 2 years; OR = 3.93, 95% CI = 1.26–12.22; P = 0.018), fewer unsupervised doses (≤ 8 doses past‐month versus no take‐aways; OR = 0.50; 95% CI = 0.27–0.93; P = 0.028) and longer travel distance (≥ 5 versus < 5 km; OR = 2.10, 95% CI = 1.20–3.65; P = 0.009). Sixty‐nine per cent reported ‘no problems or concerns’ with potential differences in availability, flexibility and location of XR‐buprenorphine. Conclusions Among regular opioid users in Australia, perceptions of extended‐release buprenorphine as a good treatment option are associated with being female, recent illicit drug use and factors relating to the (in)convenience of current opioid agonist treatment.

Background People who inject drugs (PWID) experience barriers to accessing testing and treatment for hepatitis C virus (HCV) infection. Opioid agonist therapy (OAT) may provide an opportunity to improve access to HCV care. This systematic review assessed the association of OAT and HCV testing, treatment, and treatment outcomes among PWID. Methods Bibliographic databases and conference presentations were searched for studies assessing the association between OAT and HCV testing, treatment, and treatment outcomes [direct-acting antiviral (DAA) therapy only] among people who inject drugs (in the past year). Meta-analysis was used to pool estimates. Results Among 9,877 articles identified, 22 studies conducted in Australia, Europe, North America, and Thailand were eligible and included. Risk of bias was serious in 21 studies and moderate in one study. Current/recent OAT was associated with an increased odds of recent HCV antibody testing [4 studies; odds ratio (OR), 1.80; 95% CI:1.36, 2.39), HCV RNA testing among those who were HCV antibody positive (2 studies; OR, 1.83; 95% CI:1.27, 2.62), and DAA treatment uptake among those who were HCV RNA positive (7 studies; OR 1.53; 95% CI: 1.07, 2.20). There was insufficient evidence of an association between OAT and treatment completion (9 studies) or sustained virologic response following DAA therapy (9 studies). Conclusions Opioid agonist therapy can increase linkage to HCV care, including uptake of HCV testing and treatment among PWID. This supports the scale-up of OAT as part of strategies to enhance HCV treatment to further HCV elimination efforts.

Background and aims Amphetamines are the second most commonly used class of illicit drugs. We aimed to produce pooled estimates of mortality risks among people with regular or dependent use of amphetamines, with a focus upon all‐cause mortality as well as specific causes of death. Design Systematic review and meta‐analysis of cohorts of people with problematic use or dependence on amphetamines with data on all‐cause or cause‐specific mortality. Setting and participants Of 4240 papers, 30 were eligible, reporting on 25 cohorts that measured all‐cause mortality, drug poisoning, suicide, accidental injuries, homicide and cardiovascular mortality. Cohorts (n = 35–74 139) were in North America, several Nordic countries and Asia Pacific. Measurement Titles/abstracts were independently screened by one reviewer and excluded those reviewed by a second reviewer. Full‐text screening was by two reviewers with discrepancies resolved via a third reviewer. We extracted data on crude mortality rates (CMR) per 100 person‐years (py), standardized mortality ratios (SMRs). We imputed SMRs where possible if not reported by study authors. We also calculated mortality relative risks. Data were pooled using random‐effects models; potential reasons for heterogeneity were explored using subgroup analyses and meta‐regressions. Findings Twenty‐three cohorts contributed data for the pooled all‐cause CMR: 1.14 per 100 py [95% confidence interval (CI) = 0.92–1.42]. Pooled cause‐specific mortality rates were: drug poisoning, 0.14 per 100 py (95% CI = 0.06–0.34); cardiovascular disease, 0.13 per 100 py (95% CI = 0.06–0.29); suicide, 0.20 per 100 py (95% CI = 0.07–0.55); accidental injury, 0.20 per 100 py (95% CI = 0.08–0.47) and homicide, 0.03 per 100 py (95% CI = 0.02–0.06). There was substantial heterogeneity for all pooled CMR estimates except homicide. The pooled all‐cause SMR was 6.83 (95% CI = 5.27–8.84). Pooled cause‐specific SMRS were: poisoning, 24.70 (95% CI = 16.67, 36.58); homicide, 11.90 (95% CI = 7.82–18.12); suicide, 12.20 (95% CI = 4.89–30.47); cardiovascular disease, 5.12 (95% CI = 3.74–7.00) and accidental injury, 5.12 (95% CI = 2.88–9.08). Conclusions People with regular or dependent amphetamine use are at elevated risk of a range of causes of mortality compared with people without regular or dependent amphetamine use.