Dataset Information

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.

ABSTRACT:

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.

SUBMITTER: Santo T

PROVIDER: S-EPMC8173472 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Santo Thomas T Clark Brodie B Hickman Matt M Grebely Jason J Campbell Gabrielle G Sordo Luis L Chen Aileen A Tran Lucy Thi LT Bharat Chrianna C Padmanathan Prianka P Cousins Grainne G Dupouy Julie J Kelty Erin E Muga Roberto R Nosyk Bohdan B Min Jeong J Pavarin Raimondo R Farrell Michael M Degenhardt Louisa L

JAMA psychiatry 20210901 9

<h4>Importance</h4>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.<h4>Objective</h4>To estimate the association of time receiving OAT with mortality.<h4>Data sources</h4>The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, in ...[more]

PMID: 34076676

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Project description:BackgroundMortality is increased among people with opioid use disorder but reduced while on opioid agonist treatment (OAT). However, the impact of patient and treatment characteristics on mortality and causes of death is insufficiently studied.ObjectivesThe objective of this study was to explore mortality and causes of death and examine the impact of patient and treatment characteristics on mortality in an OAT cohort with high retention in treatment.MethodsDesign: longitudinal cohort study.SettingNorway. Observation period: time from OAT start as of 1998 until death or end of 2016, 2,508 person-years (PY) in total.Sample200 persons starting OAT 1998-2007.Data sourceshospital records, interviews, the Norwegian Cause of Death Registry, Statistics Norway.ResultsRetention: 86.4% of the observation period was on OAT, 9.0% off, 4.6% unknown OAT status. All-cause crude mortality rate per 100 PY during the whole observation period was 1.64 (95% CI: 1.19-2.20), for deaths of somatic cause 0.88 (0.56-1.31), for drug-induced deaths 0.44 (0.23-0.76), and traumatic deaths 0.24 (0.10-0.50). Off-versus-on-OAT all-cause mortality ratio was 2.31 (1.00-4.85). On OAT, 58% of the deaths were of somatic cause and 21% drug-induced; off OAT, 38% of somatic cause and 50% drug-induced. Increasing baseline age and rate of somatic hospital treatment episodes were independently associated with increased all-cause mortality risk, while increasing rate of in-patient psychiatric treatment episodes was associated with reduced risk. Increasing duration of nicotine and cannabis use and alcohol dependence as well as increasing severity of polydrug use were associated with increased all-cause and somatic mortality adjusted for age and sex.ConclusionThe long observation period made it possible to demonstrate the importance of long-term retention in OAT to reduce mortality. Further, the preponderance of somatic and reduction of drug-induced causes of death during OAT underlines the need for follow-up of chronic diseases and health-promoting lifestyle changes. These findings add to the knowledge about long-term OAT effects, not least in ageing OAT populations.

Project description:ImportanceExtramedical opioid use has escalated in recent years. A better understanding of cause-specific mortality in this population is needed to inform comprehensive responses.ObjectiveTo 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 sourcesFor 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 selectionCohort studies of people using extramedical opioids and reporting mortality outcomes were screened for inclusion independently by 2 team members.Data extraction and synthesisData 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 measuresOutcome 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.ResultsOf 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 relevanceThe 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.

Project description:ObjectiveBipolar disorder (BD) is associated with premature mortality. All-cause and specific mortality risks in this population remain unclear, and more studies are still needed to further understand this issue and guide individual and public strategies to prevent mortality in bipolar disorder Thus, a systematic review and meta-analysis of studies assessing mortality risk in people with BD versus the general population was conducted. The primary outcome was all-cause mortality, whilst secondary outcomes were mortality due to suicide, natural, unnatural, and specific-causes mortality.ResultsFifty-seven studies were included (BD; n = 678,353). All-cause mortality was increased in people with BD (RR = 2.02, 95% CI: 1.89-2.16, k = 39). Specific-cause mortality was highest for suicide (RR = 11.69, 95% CI: 9.22-14.81, k = 25). Risk of death due to unnatural causes (RR = 7.29, 95% CI: 6.41-8.28, k = 17) and natural causes (RR = 1.90, 95% CI: 1.75-2.06, k = 17) were also increased. Among specific natural causes analyzed, infectious causes had the higher RR (RR = 4,38, 95%CI: 1.5-12.69, k = 3), but the analysis was limited by the inclusion of few studies. Mortality risk due to respiratory (RR = 3.18, 95% CI: 2.55-3.96, k = 6), cardiovascular (RR = 1.76, 95% CI: 1.53-2.01, k = 27), and cerebrovascular (RR = 1.57, 95% CI: 1.34-1.84, k = 13) causes were increased as well. No difference was identified in mortality by cancer (RR = 0.99, 95% CI: 0.88-1.11, k = 16). Subgroup analyses and meta-regression did not affect the findings.ConclusionResults presented in this meta-analysis show that risk of premature death in BD is not only due to suicide and unnatural causes, but somatic comorbidities are also implicated. Not only the prevention of suicide, but also the promotion of physical health and the prevention of physical conditions in individuals with BD may mitigate the premature mortality in this population. Notwithstanding this is to our knowledge the largest synthesis of evidence on BD-related mortality, further well-designed studies are still warranted to inform this field.

Project description:ImportanceA recent increase in patients presenting with nonfatal opioid overdoses has focused clinical attention on characterizing their risks of premature mortality.ObjectiveTo describe all-cause mortality rates, selected cause-specific mortality rates, and standardized mortality rate ratios (SMRs) of adults during their first year after nonfatal opioid overdose.Design, setting, and participantsThis US national longitudinal study assesses a cohort of patients aged 18 to 64 years who were Medicaid beneficiaries and experienced nonfatal opioid overdoses. The Medicaid data set included the years 2001 through 2007. Death record information was obtained from the National Death Index. Data analysis occurred from October 2017 to January 2018.Main outcomes and measuresCrude mortality rates per 100 000 person-years were determined in the first year after nonfatal opioid overdose. Standardized mortality rate ratios (SMR) were estimated for all-cause and selected cause-specific mortality standardized to the general population with respect to age, sex, and race/ethnicity.ResultsThe primary cohort included 76 325 adults and 66 736 person-years of follow-up. During the first year after nonfatal opioid overdose, there were 5194 deaths, the crude death rate was 778.3 per 10 000 person-years, and the all-cause SMR was 24.2 (95% CI, 23.6-24.9). The most common immediate causes of death were substance use-associated diseases (26.2%), diseases of the circulatory system (13.2%), and cancer (10.3%). For every cause examined, SMRs were significantly elevated, especially with respect to drug use-associated diseases (SMR, 132.1; 95% CI, 125.6-140.0), HIV (SMR, 45.9; 95% CI, 39.5-53.0), chronic respiratory diseases (SMR, 41.1; 95% CI, 36.0-46.8), viral hepatitis (SMR, 30.6; 95% CI, 22.9-40.2), and suicide (SMR, 25.9; 95% CI, 22.6-29.6), particularly including suicide among females (SMR, 47.9; 95% CI, 39.8-52.3).Conclusions and relevanceIn a US national cohort of adults who had experienced a nonfatal opioid overdose, a marked excess of deaths was attributable to a wide range of substance use-associated, mental health, and medical conditions, underscoring the importance of closely coordinating the substance use, mental health, and medical care of this patient population.

Project description:BackgroundFew studies have assessed the association between hypertension and risk of detailed causes of death. We investigated the association between hypertension and all-cause mortality and 67 causes of death in a large cohort.MethodsMultivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for self-reported hypertension vs. no hypertension and mortality. Adults aged ≥18 years (n = 213798) were recruited in 1997-2004 and followed through December 31, 2006.ResultsDuring 5.81 years of follow-up, 11254 deaths occurred. Self-reported hypertension vs. no hypertension was associated with increased risk of all-cause mortality (HR = 1.25, 95% CI: 1.19-1.31) and mortality from septicemia (HR =1.66, 1.06-2.59), other infectious parasitic diseases (HR = 2.67, 1.09-6.51), diabetes mellitus (HR = 1.97, 1.45-2.67), circulatory disease (HR = 1.49, 1.37-1.61), hypertensive heart disease (HR = 3.23, 2.00-5.20), ischemic heart disease (HR = 1.35, 1.23-1.49), acute myocardial infarction (HR = 1.50, 1.27-1.77), other chronic ischemic heart diseases (HR = 1.35, 1.17-1.56), all other forms of heart disease (HR = 1.51, 1.21-1.89), primary hypertension and renal disease (HR = 3.11, 1.82-5.30), cerebrovascular disease (HR = 1.64, 1.37-1.97), other circulatory system diseases (HR = 1.71, 1.09-2.69), other chronic lower respiratory diseases (HR = 1.39, 1.12-1.73), other chronic liver disease (HR = 1.89, 1.06-3.37), renal failure (HR = 1.91, 1.33-2.74), motor vehicle accidents (HR = 1.60, 1.07-2.37), and all other diseases (HR =1.30, 1.10-1.54), but with lower risk of uterine cancer (HR = 0.37, 95% CI: 0.15-0.90) and Alzheimer's disease (HR = 0.65, 95% CI: 0.47-0.92).ConclusionHypertension was associated with increased risk of all-cause mortality and 17 out of 67 causes of death, with most of these being circulatory disease outcomes, however, some of the remaining associations are unlikely to be causal. Further studies are needed to clarify associations with less common causes of death and potential causality across outcomes.

Dataset Information

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

Objective

Data sources

Study selection

Data extraction and synthesis

Main outcomes and measures

Results

Conclusions and relevance

Publications

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.

Similar Datasets

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