Keith Humphreys

<b>Objectives</b>&nbsp;To identify trends in concurrent use of a benzodiazepine and an opioid and to identify the impact of these trends on admissions to hospital and emergency room visits for opioid overdose. <b>Design</b>&nbsp;Retrospective analysis of claims data, 2001-13. <b>Setting</b>&nbsp;Administrative health claims database. <b>Participants</b>&nbsp;315 428 privately insured people aged 18-64 who were continuously enrolled in a health plan with medical and pharmacy benefits during the study period and who also filled at least one prescription for an opioid. <b>Interventions</b>&nbsp;Concurrent benzodiazepine/opioid use, defined as an overlap of at least one day in the time periods covered by prescriptions for each drug. <b>Main outcome measures</b>&nbsp;Annual percentage of opioid users with concurrent benzodiazepine use; annual incidence of visits to emergency room and inpatient admissions for opioid overdose. <b>Results</b>&nbsp;9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users. Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P&lt;0.001) among all opioid users. The adjusted odds ratio for an emergency room visit or inpatient admission for opioid overdose was 1.42 (1.33 to 1.51; P&lt;0.001) for intermittent opioid users and 1.81 (1.67 to 1.96; P&lt;0.001) chronic opioid users. If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16). <b>Conclusions</b>&nbsp;From 2001 to 2013, concurrent benzodiazepine/opioid use sharply increased in a large sample of privately insured patients in the US and significantly contributed to the overall population risk of opioid overdose.

AIMS: Although debates over the efficacy of oral naltrexone and acamprosate in treating alcohol use disorders tend to focus on their global efficacy relative to placebo or their efficacy relative to each other, the underlying reality may be more nuanced. This meta-analysis examined when naltrexone and acamprosate are most helpful by testing: (i) the relative efficacy of each medication given its presumed mechanism of action (reducing heavy drinking versus fostering abstinence) and (ii) whether different ways of implementing each medication (required abstinence before treatment, detoxification before treatment, goal of treatment, length of treatment, dosage) moderate its effects. METHODS: A systematic literature search identified 64 randomized, placebo-controlled, English-language clinical trials completed between 1970 and 2009 focused on acamprosate or naltrexone. RESULTS: Acamprosate had a significantly larger effect size than naltrexone on the maintenance of abstinence, and naltrexone had a larger effect size than acamprosate on the reduction of heavy drinking and craving. For naltrexone, requiring abstinence before the trial was associated with larger effect sizes for abstinence maintenance and reduced heavy drinking compared with placebo. For acamprosate, detoxification before medication administration was associated with better abstinence outcomes compared with placebo. CONCLUSIONS: In treatment for alcohol use disorders, acamprosate has been found to be slightly more efficacious in promoting abstinence and naltrexone slightly more efficacious in reducing heavy drinking and craving. Detoxification before treatment or a longer period of required abstinence before treatment is associated with larger medication effects for acamprosate and naltrexone respectively.

BACKGROUND: Alcohol use disorder (AUD) confers a prodigious burden of disease, disability, premature mortality, and high economic costs from lost productivity, accidents, violence, incarceration, and increased healthcare utilization. For over 80 years, Alcoholics Anonymous (AA) has been a widespread AUD recovery organization, with millions of members and treatment free at the point of access, but it is only recently that rigorous research on its effectiveness has been conducted. OBJECTIVES: To evaluate whether peer-led AA and professionally-delivered treatments that facilitate AA involvement (Twelve-Step Facilitation (TSF) interventions) achieve important outcomes, specifically: abstinence, reduced drinking intensity, reduced alcohol-related consequences, alcohol addiction severity, and healthcare cost offsets. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, CINAHL and PsycINFO from inception to 2 August 2019. We searched for ongoing and unpublished studies via ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 15 November 2018. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and bibliographies of included studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-RCTs and non-randomized studies that compared AA or TSF (AA/TSF) with other interventions, such as motivational enhancement therapy (MET) or cognitive behavioral therapy (CBT), TSF treatment variants, or no treatment. We also included healthcare cost offset studies. Participants were non-coerced adults with AUD. DATA COLLECTION AND ANALYSIS: We categorized studies by: study design (RCT/quasi-RCT; non-randomized; economic); degree of standardized manualization (all interventions manualized versus some/none); and comparison intervention type (i.e. whether AA/TSF was compared to an intervention with a different theoretical orientation or an AA/TSF intervention that varied in style or intensity). For analyses, we followed Cochrane methodology calculating the standard mean difference (SMD) for continuous variables (e.g. percent days abstinent (PDA)) or the relative risk (risk ratios (RRs)) for dichotomous variables. We conducted random-effects meta-analyses to pool effects wherever possible. MAIN RESULTS: We included 27 studies containing 10,565 participants (21 RCTs/quasi-RCTs, 5 non-randomized, and 1 purely economic study). The average age of participants within studies ranged from 34.2 to 51.0 years. AA/TSF was compared with psychological clinical interventions, such as MET and CBT, and other 12-step program variants. We rated selection bias as being at high risk in 11 of the 27 included studies, unclear in three, and as low risk in 13. We rated risk of attrition bias as high risk in nine studies, unclear in 14, and low in four, due to moderate (> 20%) attrition rates in the study overall (8 studies), or in study treatment group (1 study). Risk of bias due to inadequate researcher blinding was high in one study, unclear in 22, and low in four. Risks of bias arising from the remaining domains were predominantly low or unclear. AA/TSF (manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) RCTs comparing manualized AA/TSF to other clinical interventions (e.g. CBT), showed AA/TSF improves rates of continuous abstinence at 12 months (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 2 studies, 1936 participants; high-certainty evidence). This effect remained consistent at both 24 and 36 months. For percentage days abstinent (PDA), AA/TSF appears to perform as well as other clinical interventions at 12 months (mean difference (MD) 3.03, 95% CI -4.36 to 10.43; 4 studies, 1999 participants; very low-certainty evidence), and better at 24 months (MD 12.91, 95% CI 7.55 to 18.29; 2 studies, 302 participants; low-certainty evidence) and 36 months (MD 6.64, 95% CI 1.54 to 11.75; 1 study, 806 participants; low-certainty evidence). For longest period of abstinence (LPA), AA/TSF may perform as well as comparison interventions at six months (MD 0.60, 95% CI -0.30 to 1.50; 2 studies, 136 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at 12 months, as measured by drinks per drinking day (DDD) (MD -0.17, 95% CI -1.11 to 0.77; 1 study, 1516 participants; moderate-certainty evidence) and percentage days heavy drinking (PDHD) (MD -5.51, 95% CI -14.15 to 3.13; 1 study, 91 participants; low-certainty evidence). For alcohol-related consequences, AA/TSF probably performs as well as other clinical interventions at 12 months (MD -2.88, 95% CI -6.81 to 1.04; 3 studies, 1762 participants; moderate-certainty evidence). For alcohol addiction severity, one study found evidence of a difference in favor of AA/TSF at 12 months (P < 0.05; low-certainty evidence). AA/TSF (non-manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) For the proportion of participants completely abstinent, non-manualized AA/TSF may perform as well as other clinical interventions at three to nine months follow-up (RR 1.71, 95% CI 0.70 to 4.18; 1 study, 93 participants; low-certainty evidence). Non-manualized AA/TSF may also perform slightly better than other clinical interventions for PDA (MD 3.00, 95% CI 0.31 to 5.69; 1 study, 93 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at nine months, as measured by DDD (MD -1.76, 95% CI -2.23 to -1.29; 1 study, 93 participants; very low-certainty evidence) and PDHD (MD 2.09, 95% CI -1.24 to 5.42; 1 study, 286 participants; low-certainty evidence). None of the RCTs comparing non-manualized AA/TSF to other clinical interventions assessed LPA, alcohol-related consequences, or alcohol addiction severity. Cost-effectiveness studies In three studies, AA/TSF had higher healthcare cost savings than outpatient treatment, CBT, and no AA/TSF treatment. The fourth study found that total medical care costs decreased for participants attending CBT, MET, and AA/TSF treatment, but that among participants with worse prognostic characteristics AA/TSF had higher potential cost savings than MET (moderate-certainty evidence). AUTHORS' CONCLUSIONS: There is high quality evidence that manualized AA/TSF interventions are more effective than other established treatments, such as CBT, for increasing abstinence. Non-manualized AA/TSF may perform as well as these other established treatments. AA/TSF interventions, both manualized and non-manualized, may be at least as effective as other treatments for other alcohol-related outcomes. AA/TSF probably produces substantial healthcare cost savings among people with alcohol use disorder.

BACKGROUND AND AIMS: One of the challenges of international alcohol research and policy is the variability in and lack of knowledge of how governments in different nations define a standard drink and low-risk drinking. This study gathered such information from governmental agencies in 37 countries. METHODS: A pool of 75 countries that might have definitions was created using World Health Organization (WHO) information and the authors' own judgement. Structured internet searches of relevant terms for each country were supplemented by efforts to contact government agencies directly and to consult with alcohol experts in the country. RESULTS: Most of the 75 national governments examined were not identified as having adopted a standard drink definition. Among the 37 that were so identified, the modal standard drink size was 10 g pure ethanol, but variation was wide (8-20 g). Significant variability was also evident for low-risk drinking guidelines, ranging from 10-42 g per day for women and 10-56 g per day for men to 98-140 g per week for women and 150-280 g per week for men. CONCLUSIONS: Researchers working and communicating across national boundaries should be sensitive to the substantial variability in 'standard' drink definitions and low-risk drinking guidelines. The potential impact of guidelines, both in general and in specific national cases, remains an important question for public health research.

AIMS: This study tested the hypothesis that the relationship between Alcoholics Anonymous (AA) involvement and reduced substance use is partially explained (or 'mediated') by changes in social networks. DESIGN: This is a naturalistic longitudinal study of the course of alcohol problems. SETTING: Study sites were the 10 largest public and private alcohol treatment programs in a northern California county. PARTICIPANTS: Three hundred and seventy-seven men and 277 women were recruited upon seeking treatment at study sites. MEASUREMENTS: At baseline and 1-year follow-up, we assessed alcohol consequences and dependence symptoms, consumption, social support for abstinence, pro-drinking social influences and AA involvement. FINDINGS: In the structural equation model, AA involvement was a significant predictor of lower alcohol consumption and fewer related problems. The size of this effect decreased by 36% when network size and support for drinking were included as mediators. In logistic regression models predicting abstinence at follow-up, AA remained highly significant after including social network variables but was again reduced in magnitude. Thirty-day abstinence was predicted by AA involvement (OR=2.9), not having pro-drinking influences in one's network (OR=0.7) and having support for reducing consumption from people met in AA (versus no support; OR=3.4). In contrast, having support from non-AA members was not a significant predictor of abstinence. For alcohol-related outcomes other than abstinence, significant relationships were found for both AA-based and non-AA-based support. CONCLUSIONS: The type of social support specifically given by AA members, such as 24-hour availability, role modeling and experientially based advice for staying sober, may help to explain AA's mechanism of action. Results highlight the value of focusing on outcomes reflective of AA's goals (such as abstinence) when studying how AA works.