Association Between Opioid Agonist Therapy and Testing, Treatment Uptake, and Treatment Outcomes for Hepatitis C Infection Among People Who Inject Drugs: A Systematic Review and Meta-analysis.

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 that assessed the association between OAT and HCV testing, treatment, and treatment outcomes (direct-acting antiviral [DAA] therapy only) among PWID (in the past year). Meta-analysis was used to pool estimates. RESULTS: Of 9877 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 1 study. Current/recent OAT was associated with an increased odds of recent HCV antibody testing (4 studies; odds ratio (OR), 1.80; 95% confidence interval [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: OAT 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.

Responding to global stimulant use: challenges and opportunities.

We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.

All-Cause and Overdose Mortality Risk Among People Prescribed Opioids: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate all-cause and overdose crude mortality rates and standardized mortality ratios among people prescribed opioids for chronic noncancer pain and risk of overdose death in this population relative to people with similar clinical profiles but not prescribed opioids. DESIGN: Systematic review and meta-analysis. METHODS: Medline, Embase, and PsycINFO were searched in February 2018 and October 2019 for articles published beginning 2009. Due to limitations in published studies, we revised our inclusion criteria to include cohort studies of people prescribed opioids, excluding those studies where people were explicitly prescribed opioids for the treatment of opioid use disorder or acute cancer or palliative pain. We estimated pooled all-cause and overdose crude mortality rates using random effects meta-analysis models. No studies reported standardized mortality ratios or relative risks. RESULTS: We included 13 cohorts with 6,029,810 participants. The pooled all-cause crude mortality rate, based on 10 cohorts, was 28.8 per 1000 person-years (95% CI = 17.9-46.4), with substantial heterogeneity (I2 = 99.9%). The pooled overdose crude mortality rate, based on six cohorts, was 1.1 per 1000 person-years (95% CI = 0.4-3.4), with substantial heterogeneity (I2 = 99.5%), but indications for opioid prescribing and opioid exposure were poorly ascertained. We were unable to estimate mortality in this population relative to clinically similar populations not prescribed opioids. CONCLUSIONS: Methodological limitations in the identified literature complicate efforts to determine the overdose mortality risk of people prescribed opioids. There is a need for large-scale clinical trials to assess adverse outcomes in opioid prescribing, especially for chronic noncancer pain.

Interaction between Digestive Strategy and Niche Specialization Predicts Speciation Rates across Herbivorous Mammals.

Biotic and abiotic factors often are treated as mutually exclusive drivers of diversification processes. In this framework, ecological specialists are expected to have higher speciation rates than generalists if abiotic factors are the primary controls on species diversity but lower rates if biotic interactions are more important. Speciation rate is therefore predicted to positively correlate with ecological specialization in the purely abiotic model but negatively correlate in the biotic model. In this study, I show that the positive relationship between ecological specialization and speciation expected from the purely abiotic model is recovered only when a species-specific trait, digestive strategy, is modeled in the terrestrial, herbivorous mammals (Mammalia). This result suggests a more nuanced model in which the response of specialized lineages to abiotic factors is dependent on a biological trait. I also demonstrate that the effect of digestive strategy on the ecological specialization-speciation rate relationship is not due to a difference in either the degree of ecological specialization or the speciation rate between foregut- and hindgut-fermenting mammals. Together, these findings suggest that a biological trait, alongside historical abiotic events, played an important role in shaping mammal speciation at long temporal and large geographic scales.

The role of ecological opportunity in shaping disparate diversification trajectories in a bicontinental primate radiation.

Exceptional species and phenotypic diversity commonly are attributed to ecological opportunity (EO). The conventional EO model predicts that rates of lineage diversification and phenotypic evolution are elevated early in a radiation only to decline later in response to niche availability. Foregut fermentation is hypothesized to be a key innovation that allowed colobine monkeys (subfamily Colobinae), the only primates with this trait, to successfully colonize folivore adaptive zones unavailable to other herbivorous species. Therefore, diversification rates also are expected to be strongly linked with the evolution of traits related to folivory in these monkeys. Using dated molecular phylogenies and a dataset of feeding morphology, I test predictions of the EO model to evaluate the role of EO conferred by foregut fermentation in shaping the African and Asian colobine radiations. Findings from diversification methods coupled with colobine biogeographic history provide compelling evidence that decreasing availability of new adaptive zones during colonization of Asia together with constraints presented by dietary specialization underlie temporal changes in diversification in the Asian but not African clade. Additionally, departures from the EO model likely reflect iterative diversification events in Asia.

Do estimated and actual species phylogenies match? Evaluation of East African cichlid radiations.

A large number of published phylogenetic estimates are based on a single locus or the concatenation of multiple loci, even though genealogies of single or concatenated loci may not accurately reflect the true history of species diversification (i.e., the species tree). The increased availability of genomic data, coupled with new computational methods, improves resolution of species relationships beyond what was possible in the past. Such developments will no doubt benefit future phylogenetic studies. It remains unclear how robust phylogenies that predate these developments (i.e., the bulk of phylogenetic studies) are to departures from the assumption of strict gene tree-species tree concordance. Here, we present a parametric bootstrap (PBST) approach that assesses the reliability of past phylogenetic estimates in which gene tree-species tree discord was ignored. We focus on a universal cause of discord-the random loss of gene lineages from genetic drift-and apply the method in a meta-analysis of East African cichlids, a group encompassing historical scenarios that are particularly challenging for phylogenetic estimation. Although we identify some evolutionary relationships that are robust to gene tree discord, many past phylogenetic estimates of cichlids are not. We discuss the utility of the PBST method for evaluating the robustness of gene tree-based phylogenetic estimations in general as well as for testing the clade-specific performance of species tree estimation methods and designing sampling strategies that increase the accuracy of estimated species relationships.

Prevalence of comorbid substance use disorders among people with opioid use disorder: A systematic review & meta-analysis.

BACKGROUND: Comorbid substance use disorders (SUDs) among people with opioid use disorder (OUD) contribute to poor clinical outcomes, including overdose and mortality. We present the first systematic review and meta-analysis to estimate the prevalence of specific non-opioid SUDs among people with OUD. METHODS: We searched Embase, PsycINFO, and MEDLINE from 1990 to 2022 for studies that used Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) criteria to assess the prevalence of non-opioid SUDs among individuals with OUD. We used random-effects meta-analyses with 95% Confidence Intervals (CIs) to pool current and lifetime prevalence estimates separately. Meta-regressions and stratified meta-analyses were used to examine differences in prevalence estimates by sample characteristics and methodological factors. RESULTS: Of the 36,971 publications identified, we included data from 194 studies and 77,212 participants with OUD. The prevalence of any comorbid SUD among people with OUD was 59.5% (95%CI 49.1-69.5%) for current non-opioid SUDs, with 72.0% (95%CI 52.5-87.9%) experiencing a comorbid SUD in their lifetime. Of the studies that examined current comorbid SUDs, cocaine use disorder (30.5%, 95%CI 23.0-38.7%) was most common, followed by alcohol (27.1%, 95%CI 24.4- 30.0%), cannabis (22.7%, 95%CI 19.0-26.6%), sedative (16.1%, 95%CI 13.1-19.3%), and methamphetamine (11.4%, 95%CI 6.8-17.1%) use disorders. Substantial heterogeneity (I2>90%) across estimates was observed. Substantial heterogeneity (I2>90%) was observed across estimates, with significant variations in prevalence identified across geographic locations, recruitment settings, and other study-level factors. CONCLUSION: Findings from this study emphasize the importance of comorbid SUD treatment access for people with OUD. Our estimates can inform the provision of treatment and harm reduction strategies for people with OUD and specific subpopulations.

Interventions to reduce harms related to drug use among people who experience incarceration: systematic review and meta-analysis.

BACKGROUND: Mortality, suicide, self-harm, and substance use are elevated among people who are incarcerated. There is a wide range of heterogeneous interventions aimed at reducing these harms in this population. Previous reviews have focused on specific interventions or limited their findings to drug use and recidivism and have not explored interventions delivered after release from prison. Our aim is to examine the effect of interventions delivered to people who use drugs during incarceration or after release from incarceration, on a wide range of outcomes. METHODS: In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO databases up until Sept 12, 2023 for studies published from Jan 1, 1980 onwards. All studies evaluating the effectiveness of any intervention on drug use, recidivism outcomes, sexual or injecting risk behaviours, or mortality among people who use psychoactive drugs and who were currently or recently incarcerated were included. Studies without a comparator or measuring only alcohol use were excluded. Data extracted from each study included demographic characteristics, interventions, and comparisons. Pooled odds ratios and risk ratios were calculated using random-effects meta-analyses. FINDINGS: We identified 126 eligible studies (47 randomised controlled trials and 79 observational studies) encompassing 18 interventions; receiving opioid-agonist treatment (OAT) in prison reduced the risk of death in prison (one study; hazard ratio 0·25; 95% CI 0·13-0·48), whereas receiving OAT in the first 4 weeks following release reduced risk of death in the community (two studies; relative risk 0·24; 95% CI 0·15-0·37). Therapeutic community interventions reduced re-arrest at 6-12 months (six studies; odds ratio [OR] 0·72; 95% CI 0·55-0·95) and reincarceration at 24 months (two studies; OR 0·66; 95% CI 0·48-0·96). There was scarce evidence that OAT and syringe service provision are effective in reducing injecting risk behaviours and needle and syringe sharing. INTERPRETATION: There are effective interventions to reduce mortality and recidivism for people who use drugs who have been incarcerated. Nonetheless, there are also substantial gaps in the research examining the effect of interventions on risk behaviours and mortality during incarceration and a need for randomised designs examining outcomes for people who use drugs after release. FUNDING: Australian National Health and Medical Research Council.

The prevalence of gambling and problematic gambling: a systematic review and meta-analysis.

BACKGROUND: Gambling behaviours have become of increased public health interest, but data on prevalence remain scarce. In this study, we aimed to estimate for adults and adolescents the prevalence of any gambling activity, the prevalence of engaging in specific gambling activities, the prevalence of any risk gambling and problematic gambling, and the prevalence of any risk and problematic gambling by gambling activity. METHODS: We performed a systematic review and meta-analysis. We systematically searched for peer-reviewed literature (on MEDLINE, Embase, and PsycInfo) and grey literature to identify papers published between Jan 1, 2010, and March 4, 2024. We searched for any gambling, including engagement with individual gambling activities, and problematic gambling data among adults and adolescents. We included papers that reported the prevalence or proportion of a gambling outcome of interest. We excluded papers of non-original data or based on a biased sample. Data were extracted into a bespoke Microsoft Access database, with the Joanna Briggs Institute Critical Appraisal Tool used to identify the risk of bias for each sample. Representative population survey estimates were firstly meta-analysed into country-level prevalence estimates, using metaprop, of any gambling, any risk gambling, problematic gambling, and by gambling activity. Secondly, population-weighted regional-level and global estimates were generated for any gambling, any risk gambling, problematic gambling, and specific gambling activity. This review is registered on PROSPERO (CRD42021251835). FINDINGS: We screened 3692 reports, with 380 representative unique samples, in 68 countries and territories. Overall, the included samples consisted of slightly more men or male individuals, with a mean age of 29·72 years, and most samples identified were from high-income countries. Of these samples, 366 were included in the meta-analysis. Globally, 46·2% (95% CI 41·7-50·8) of adults and 17·9% (14·8-21·2) of adolescents had gambled in the past 12 months. Rates of gambling were higher among men (49·1%; 45·5-52·6) than women (37·4%; 32·0-42·5). Among adults, 8·7% (6·6-11·3) were classified as engaging in any risk gambling, and 1·41% (1·06-1·84) were engaging in problematic gambling. Among adults, rates of problematic gambling were greatest among online casino or slots gambling (15·8%; 10·7-21·6). There were few data reported on any risk and problematic gambling among adolescent samples. INTERPRETATION: Existing evidence suggests that gambling is prevalent globally, that a substantial proportion of the population engage in problematic gambling, and that rates of problematic gambling are greatest among those gambling on online formats. Given the growth of the online gambling industry and the association between gambling and a range of public health harms, governments need to give greater attention to the strict regulation and monitoring of gambling globally. FUNDING: Australian National Health and Medical Research Council.

Preventable Deaths Attributable to Second-Hand Smoke in Southeast Asia-Analysis of the Global Burden of Disease Study 2019.

Objectives: In addition to harms caused to individuals who smoke, second-hand smoke (SHS or passive smoke) is an important public health issue. We aim to estimate the extent of preventable deaths due to tobacco and SHS exposure in Southeast Asia. Methods: Data were from the Global Burden of Disease Study 2019. We analysed data from Southeast Asia, including Cambodia, Indonesia, Laos, Malaysia, Maldives, Mauritius, Myanmar, Philippines, Seychelles, Sri Lanka, Thailand, Timor-Leste, and Vietnam. Results: In 2019, there were 728,500 deaths attributable to tobacco in Southeast Asia, with 128,200 deaths attributed to SHS exposure. The leading causes of preventable deaths were ischemic heart disease, stroke, diabetes mellitus, lower respiratory infections, chronic obstructive pulmonary disease, tracheal, bronchus, and lung cancer. Among deaths attributable to tobacco, females had higher proportions of deaths attributable to SHS exposure than males in Southeast Asia. Conclusion: The burden of preventable deaths in a year due to SHS exposure in Southeast Asia is substantial. The implementation and enforcement of smoke-free policies should be prioritized to reduce the disease burden attributed to passive smoking in Southeast Asia.

Agreement between self-reported illicit drug use and biological samples: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies often rely upon self-report and biological testing methods for measuring illicit drug use, although evidence for their agreement is limited to specific populations and self-report instruments. We aimed to examine comprehensively the evidence for agreement between self-reported and biologically measured illicit drug use among all major illicit drug classes, biological indicators, populations and settings. METHODS: We systematically searched peer-reviewed databases (Medline, Embase and PsycINFO) and grey literature. Included studies reported 2 × 2 table counts or agreement estimates comparing self-reported and biologically measured use published up to March 2022. With biological results considered to be the reference standard and use of random-effect regression models, we evaluated pooled estimates for overall agreement (primary outcome), sensitivity, specificity, false omission rates (proportion reporting no use that test positive) and false discovery rates (proportion reporting use that test negative) by drug class, potential consequences attached to self-report (i.e. work, legal or treatment impacts) and time-frame of use. Heterogeneity was assessed by inspecting forest plots. RESULTS: From 7924 studies, we extracted data from 207 eligible studies. Overall agreement ranged from good to excellent (> 0.79). False omission rates were generally low, while false discovery rates varied by setting. Specificity was generally high but sensitivity varied by drug, sample type and setting. Self-report in clinical trials and situations of no consequences was generally reliable. For urine, recent (i.e. past 1-4 days) self-report produced lower sensitivity and false discovery rates than past month. Agreement was higher in studies that informed participants biological testing would occur (diagnostic odds ratio = 2.91, 95% confidence interval = 1.25-6.78). The main source of bias was biological assessments (51% studies). CONCLUSIONS: While there are limitations associated with self-report and biological testing to measure illicit drug use, overall agreement between the two methods is high, suggesting both provide good measures of illicit drug use. Recommended methods of biological testing are more likely to provide reliable measures of recent use if there are problems with self-disclosure.

Global, regional, and country-level coverage of testing and treatment for HIV and hepatitis C infection among people who inject drugs: a systematic review.

BACKGROUND: People who inject drugs are disproportionately affected by HIV and hepatitis C virus (HCV) infections, while there is little global data on HIV and HCV testing and treatment coverage of this population. We conducted a systematic review to evaluate country-level, regional, and global coverage of HIV and HCV testing and treatment among people who inject drugs. METHODS: We did a systematic review, and searched bibliographic databases (MEDLINE, Embase, and PsycINFO) and grey literature for studies published between Jan 1, 2017, and April 30, 2022, that evaluated the proportion of people who inject drugs who received testing or treatment for HIV or HCV. For each country, we estimated the proportion of people who inject drugs tested for HIV antibodies in the past 12 months (recent), people who inject drugs ever tested for HCV antibodies and HCV RNA, people who inject drugs with HIV currently receiving antiretroviral therapy, and people who inject drugs with HCV ever receiving HCV antiviral treatment. Regional and global estimates, weighted by the population size of people who inject drugs, were generated where sufficient data were available. This study is registered with PROSPERO (CRD42020173974). FINDINGS: 512 documents reported data eligible for analyses, including 337 peer-reviewed articles, 27 conference abstracts or presentations, and 148 documents from grey literature or supplementary searches. Data of recent HIV antibody testing were available for 67 countries and ever having had HCV antibody testing were available for 49 countries. Globally, an estimated 48·8% of people who inject drugs were recently tested for HIV antibodies (95% uncertainty interval [UI] 43·3-54·2%; range 0·9-86·0%), and 47·1% had ever been tested for HCV antibodies (95% UI 43·4-51·0%; range 0·0-93·3%). HCV RNA testing data were available from three countries. Coverage of HIV antibody testing was high (>75%) in four countries and for HCV antibody testing in 15 countries. The estimated uptake of current HIV treatment (18 countries) ranged from 2·6% to 81·9%, and the estimated uptake of ever having HCV treatment (23 countries) ranged from 1·8% to 88·6% across countries. Uptake of HIV treatment was high in two countries, and of HCV treatment in one country. INTERPRETATION: HIV and HCV testing and treatment uptake among people who inject drugs was highly variable, and suboptimal in most countries. Strategies to improve access to HIV and HCV care among people who inject drugs and the availability of public health surveillance are urgently required. FUNDING: Australian National Health and Medical Research Council and UK National Institute for Health and Care Research Health Protection Research Unit in Behavioural Science and Evaluation.

Epidemiology of injecting drug use, prevalence of injecting-related harm, and exposure to behavioural and environmental risks among people who inject drugs: a systematic review.

BACKGROUND: People who inject drugs are exposed to various and changing risk environments and are at risk of multiple harms related to injecting drug use (IDU). We aimed to undertake a global systematic review of the prevalence of IDU, key IDU-related harms (including HIV, hepatitis C virus [HCV], and hepatitis B virus [HBV] infection and overdose), and key sociodemographic characteristics and risk exposures for people who inject drugs. METHODS: We systematically searched for data published between Jan 1, 2017, and March 31, 2022, in databases of peer-reviewed literature (MEDLINE, Embase, and PsycINFO) and grey literature as well as various agency or organisational websites, and disseminated data requests to international experts and agencies. We searched for data on the prevalence, characteristics, and risks of people who inject drugs, including gender, age, sexuality, drug-use patterns, HIV, HCV, and HBV infections, non-fatal overdose, depression, anxiety, and injecting-related disease. Additional data were extracted from studies identified in our previous review. Meta-analyses were used to pool the data where multiple estimates were available for a country. We present country, regional, and global estimates for each variable examined. FINDINGS: We screened 40 427 reports published between 2017 and 2022, and the 871 eligible reports identified were added to the 1147 documents from the previous review. Evidence of IDU was documented in 190 of 207 countries and territories, and 14·8 million people (95% uncertainty interval [UI] 10·0-21·7) aged 15-64 years globally were estimated to inject drugs. Existing evidence suggests that there might be 2·8 million (95% UI 2·4-3·2) women and 12·1 million (95% UI 11·0-13·3) men who inject drugs globally, and that 0·4% (95% CI 0·3-1·3) of people who inject drugs identify as transgender. The amount of available data on key health and social risks among people who inject drugs varied widely across countries and regions. We estimated that 24·8% (95% CI 19·5-31·6) of people who inject drugs globally had experienced recent homelessness or unstable housing, 58·4% (95% CI 52·0-64·8) had a lifetime history of incarceration, and 14·9% (95% CI 8·1-24·3) had recently engaged in sex work, with substantial geographical variation. Injecting and sexual risk behaviour varied considerably geographically, as did risks of harms. Globally, we estimated that 15·2% (95% CI 10·3-20·9) of people who inject drugs are living with HIV, 38·8% (95% CI 31·4-46·9) have current HCV infection, 18·5% (95% CI 13·9-24·1) have recently overdosed, and 31·7% (95% CI 23·6-40·5) have had a recent skin or soft tissue infection. INTERPRETATION: IDU is being identified in a growing number of countries and territories that comprise more than 99% of the global population. IDU-related health harms are common, and people who inject drugs continue to be exposed to multiple adverse risk environments. However, quantification of many of these exposure and harms is inadequate and must be improved to allow for better targeting of harm-reduction interventions for these risks. FUNDING: Australian National Health and Medical Research Council.

Prevalence of mental disorders among people with opioid use disorder: A systematic review and meta-analysis.

BACKGROUND: Opioid use disorder (OUD) and mental disorders are major public health issues and comorbidity is common. Among people with OUD, comorbid mental disorders are associated with poorer health outcomes. To our knowledge, this is the first systematic review and meta-analysis to estimate prevalence of specific mental disorders among people with OUD. METHODS: We searched Embase, MEDLINE, and PsycInfo from 1990 to 2021 for observational studies of depression, anxiety, post-traumatic stress disorder (PTSD), bipolar, personality, and other pre-specified mental disorders among people with OUD. We pooled current and lifetime estimates of each disorder using random-effects meta-analyses with 95% Confidence Intervals (CIs). Meta-regressions and stratified analyses were used to assess heterogeneity of prevalence estimates by methodological factors and sample characteristics. FINDINGS: Of the 36,971 publications identified, we included data from 345 studies and 104,135 people with OUD in at least one pooled estimate. Among people with OUD, the prevalence of current depression was 36.1% (95%CI 32.4-39.7%), anxiety was 29.1% (95%CI 24.0-33.3%), attention-deficit/hyperactivity disorder was 20.9% (95%CI 15.7-26.2%), PTSD was 18.1% (95%CI 15.4-20.9%), and bipolar disorder was 8.7% (95%CI 6.7-10.7%). Lifetime prevalence of anti-social personality disorder was 33.6% (95%CI 29.1-38.0%) and borderline personality disorder was 18.2% (95% CI 13.4-23.1%). Sample characteristics and methodological factors, including sex, were associated with variance of multiple prevalence estimates. INTERPRETATION: Our findings emphasise the need for access to mental disorder treatment among people with OUD. Specific mental disorder estimates may inform clinical guidelines, treatment services, and future research for people with OUD, including subpopulations with distinct treatment needs.

All-cause and cause-specific mortality among people with regular or problematic cocaine use: a systematic review and meta-analysis.

AIMS: To estimate pooled all-cause and cause-specific mortality risk for people with regular or problematic cocaine use. METHODS: Systematic review and meta-analysis of prospective or retrospective cohort studies or clinical trials (n ≥30) of people with regular or problematic cocaine use with data on all-cause or cause-specific mortality. Of 2808 papers, 28 were eligible and reported on 21 cohorts, with a total 170 019 individuals. Cohorts identified based on acute care for drug poisoning or other severe health presentation were excluded. Title/abstract screening was conducted by one reviewer; a second reviewer independently checked 10% of excluded studies. Two reviewers conducted full-text screening. Data were extracted by one reviewer and checked by a second. A customized review-specific study reporting quality/risk of bias tool was used. Data on crude mortality rates (CMR) and standardized mortality ratios were extracted for both all-cause and cause-specific mortality. Standardized mortality ratios were imputed where not provided by the author using extracted data and information from the Global Burden of Disease Study 2017. Data were pooled using a random-effects model. RESULTS: The pooled all-cause crude mortality rate was 1.24 per 100 person-years [95% confidence interval (CI) = 0.86, 1.78; n = 16 cohorts], but with considerable heterogeneity (I2  = 98.8%). The pooled all-cause standardized mortality ratio (SMR) was 6.13 (95% CI = 4.15, 9.05; n = 16 cohorts). Suicide (SMR = 6.26, 95% CI = 2.84, 13.80), accidental injury (SMR = 6.36, 95% CI = 4.18, 9.68), homicide (SMR = 9.38, 95% CI 3.45-25.48) and AIDS-related mortality (SMR = 23.12, 95% CI = 11.30, 47.31) were all elevated compared with age and sex peers in the general population. CONCLUSIONS: There are elevated rates of mortality among people with regular or problematic cocaine use for traumatic deaths and deaths attributable to infectious disease.

Feasibility and acceptability of take-home naloxone for people released from prison in New South Wales, Australia.

INTRODUCTION AND AIMS: To assess the feasibility and acceptability of a take-home naloxone program for people with a history of opioid use released from prison in New South Wales, Australia. DESIGN AND METHODS: Cross-sectional interviews with people with a history of opioid use who were recently released from prison (n = 105), and semi-structured interviews with key clinical and operational staff of Justice Health and Forensic Mental Health Network and Corrective Services NSW (n = 9). RESULTS: Among people with a history of opioid use who had recently left prison, there was very high awareness of the elevated risk of overdose following release from prison (95%) and the potential for naloxone to reverse an opioid overdose (97%). Participants considered that their personal risk of overdose was low, despite ongoing opioid use being common. Participants were largely supportive of take-home naloxone, but the majority (83%) stated that proactively obtaining naloxone would be a low priority for them following release. Key informants were supportive of introducing naloxone training and supply and identified barriers to implementation, including adequate resourcing, identifying the population for training, and developing an appropriate model of training and implementation. DISCUSSION AND CONCLUSION: There was widespread support for naloxone training in custody and distribution at release among people recently released from prison and key stakeholders in health-care provision and prisons administration. As proactively accessing naloxone is a low priority for patients, naloxone supply at release may be more effective than programs that refer releasees to local pharmacies, but developing a sustainable supply model requires consideration of several barriers.

Prevalence of childhood maltreatment among people with opioid use disorder: A systematic review and meta-analysis.

BACKGROUND: Experience of childhood maltreatment (CM) is a risk factor for opioid use disorder (OUD). CM is also associated with comorbid mental disorders and poor treatment outcomes among people with OUD. To our knowledge, this is the first systematic review and meta-analysis to estimate the prevalence of CM among people with OUD. METHODS: We searched MEDLINE, EMBASE, and PsycINFO to identify observational studies that evaluated CM among people with OUD from January 1990 to June 2020. Prevalence of each CM type, sample characteristics, and methodological factors were extracted from each eligible study. Random-effects meta-analyses were used to pool prevalence estimates. Stratified meta-analyses were used to assess heterogeneity. RESULTS: Of the 6,438 publications identified, 113 studies reported quantitative CM data among people with OUD and 62 studies (k = 62; N = 21,871) were included in primary analyses. Among people with OUD, the estimated prevalence of sexual abuse was 41% (95% CI 36-47%; k = 38) among women and 16% (95% CI 12-20%; k = 25) among men. Among all people with OUD, prevalence estimates were 38% (95% CI 33-44%; k = 48) for physical abuse, 43% (95% CI 38-49%; k = 31) for emotional abuse, 38% (95% CI 30-46%; k = 17) for physical neglect, and 42% (95% CI 32-51%; k = 17) for emotional neglect. Sex, history of injecting drug use, recruitment methods, and method of assessing CM were associated with substantial heterogeneity. CONCLUSIONS: People with OUD frequently report the experience of CM, supporting the need for trauma-informed interventions among this population. Future research should consider the impact of CM on OUD presentations and when assessment is appropriate, use of validated instruments.

Association between opioid agonist therapy use and HIV testing uptake among people who have recently injected drugs: a systematic review and meta-analysis.

BACKGROUND AND AIM: Globally, nearly one in five people who inject drugs (PWID) are living with HIV, and the rate of new HIV infections in PWID is increasing in some settings. Early diagnosis is crucial for effective HIV control. We reviewed the evidence on the association between opioid agonist therapy (OAT) and HIV testing uptake among PWID. METHODS: We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand-searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Meta-analyses were conducted using random-effects models. RESULTS: Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28-2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96-4.95. CONCLUSIONS: Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade.

Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis.

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 Synthesis: This 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 Measures: Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. Results: Fifteen 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, 4.32-8.36), 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 Relevance: This 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 low. Work to improve access globally may have important population-level benefits.

All-Cause and Cause-Specific Mortality Among People Using Extramedical Opioids: A Systematic Review and Meta-analysis.

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 (I2 = 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.