Using Measurement-Based Care as a Precision Medicine Strategy for Substance Use Disorders.

PURPOSE OF REVIEW: Precision medicine prioritizes characterization of individual patient parameters to optimize care and this review evaluates measurement-based care (MBC) as a strategy for doing so in the treatment of substance use disorders (SUD). Measurement-based care refers to the systematic use of validated assessments to inform diagnosis and treatment planning, with varying frequency of assessments. Despite the seemingly obvious grounds for the use of MBC in treating SUD, systematic implementation to date has been limited. Thus, the goal of this review is to evaluate efforts to date and to stimulate greater consideration of MBC models in addictions programs. RECENT FINDINGS: Data from two published randomized controlled trials and findings from pragmatic clinical research highlight the potential utility of MBC in the SUD treatment settings. Despite these findings, the existing literature indicates the high need for larger-scale clinical trials and quality improvement programs. Potential barriers to the implementation of MBC for SUD are outlined at the patient, provider, organization, and system levels, as well as the challenges associated with the use of MBC programs for clinical research. Critical thinking considerations and risk mitigation strategies are offered toward advancing MBC for SUD beyond the current nascent state. Collectively, the existing data confirm that MBC is a suitable and promising strategy for applying a precision medicine approach in SUD treatment, warranting further implementation efforts and scientific inquiry.

Combined effect of alcohol and cannabis on simulated driving.

RATIONALE: With alcohol and cannabis remaining the most commonly detected drugs in seriously and fatally injured drivers, there is a need to understand their combined effects on driving. OBJECTIVES: The present study examined the effects of combinations of smoked cannabis (12.5% THC) and alcohol (target BrAC 0.08%) on simulated driving performance, subjective drug effects, cardiovascular measures, and self-reported perception of driving ability. METHODS: In this within-subjects, double-blind, double-dummy, placebo-controlled, randomized clinical trial, cannabis users (1-7 days/week) aged 19-29 years attended four drug administration sessions in which simulated driving, subjective effects, cardiovascular measures, and whole blood THC and metabolite concentrations were assessed following placebo alcohol and placebo cannabis (<0.1% THC), alcohol and placebo cannabis, placebo alcohol and active cannabis, and alcohol and active cannabis. RESULTS: Standard deviation of lateral position in the combined condition was significantly different from the placebo condition (p < 0.001). Standard deviation of lateral position was also significantly different from alcohol and cannabis alone conditions in the single task overall drive (p = 0.029 and p = 0.032, respectively), from the alcohol alone condition in the dual task overall drive (p = 0.022) and the cannabis alone condition in the dual task straightaway drive (p = 0.002). Compared to the placebo condition, the combined and alcohol conditions significantly increased reaction time. Subjective effects in the combined condition were significantly greater than with either of the drugs alone at some time points, particularly later in the session. A driving ability questionnaire showed that participants seemed unaware of their level of impairment. CONCLUSION: Combinations of alcohol and cannabis increased weaving and reaction time, and tended to produce greater subjective effects compared to placebo and the single drug conditions suggesting a potential additive effect. The fact that participants were unaware of this increased effect has important implications for driving safety.

Food addiction in a large community sample of Canadian adults: prevalence and relationship with obesity, body composition, quality of life and impulsivity.

BACKGROUND AND AIMS: Parallels between the persistent overconsumption of food and addictive drugs have given rise to the notion of food addiction. In a large community sample of Canadian adults, the current study examined the prevalence of food addiction and its relationship with obesity, quality of life and multiple indicators of impulsivity. A secondary goal was to analyze differences between obese and non-obese individuals with and without food addiction. DESIGN: Cross-sectional in-person assessment. SETTING: Hamilton, Ontario, Canada. PARTICIPANTS: A total of 1432 community adults (age = mean ± standard deviation = 38.93 ± 13.7; 42% male) recruited from the general community using print, bus and internet advertisements. MEASUREMENTS: Yale Food Addiction Scale 2.0, anthropometrics (including body mass index), body composition (e.g. body fat, muscle mass, body water), World Health Organization Quality of Life scale and impulsivity measures, including impulsive personality traits, delay discounting and behavioral inhibition. FINDINGS: The prevalence of food addiction was 9.3% and substantially below that of obesity (32.7%), although food addiction was significantly more common among obese individuals (18.5%, P < 0.001). Food addiction was associated with significantly lower quality of life in all domains (ßs = -0.21 to -0.34, Ps < 0.001) and significantly higher impulsive personality traits, particularly negative and positive urgency (ßs = 0.37 and 0.30, Ps < 0.001). Subgroup contrasts within both the obese and non-obese strata revealed that food addiction was associated with significantly lower quality of life in all domains (Ps < 0.001). Food addiction among non-obese individuals was also associated with higher body mass index (P < 0.001). CONCLUSION: In a general community sample, food addiction was present in slightly fewer than one in 10 individuals, approximately one-third the prevalence of obesity, but with twice the prevalence among obese individuals. Food addiction appears to be associated with substantively lower quality of life and elevations in impulsivity, particularly in deficits in emotional regulation.

Integrating a brief alcohol intervention with tobacco addiction treatment in primary care: qualitative study of health care practitioner perceptions.

BACKGROUND: Randomized trials of complex interventions are increasingly including qualitative components to further understand factors that contribute to their success. In this paper, we explore the experiences of health care practitioners in a province wide smoking cessation program (the Smoking Treatment for Ontario Patients program) who participated in the COMBAT trial. This trial examined if the addition of an electronic prompt embedded in a Clinical Decision Support System (CDSS)-designed to prompt practitioners to Screen, provide a Brief intervention and Referral to Treatment (SBIRT) to patients who drank alcohol above the amounts recommended by the Canadian Cancer Society guidelines-influenced the proportion of practitioners delivering a brief intervention to their eligible patients. We wanted to understand the factors influencing implementation and acceptability of delivering a brief alcohol intervention for treatment-seeking smokers for health care providers who had access to the CDSS (intervention arm) and those who did not (control arm). METHODS: Twenty-three health care practitioners were selected for a qualitative interview using stratified purposeful sampling (12 from the control arm and 11 from the intervention arm). Interviews were 45 to 90 min in length and conducted by phone using an interview guide that was informed by the National Implementation Research Network's Hexagon tool. Interview recordings were transcribed and coded iteratively between three researchers to achieve consensus on emerging themes. The preliminary coding structure was developed using the National Implementation Research Network's Hexagon Tool framework and data was analyzed using the framework analysis approach. RESULTS: Seventy eight percent (18/23) of the health care practitioners interviewed recognized the need to simultaneously address alcohol and tobacco use. Seventy four percent (17/23), were knowledgeable about the evidence of health risks associated with dual alcohol and tobacco use but 57% (13/23) expressed concerns with using the Canadian Cancer Society guidelines to screen for alcohol use. Practitioners acknowledged the value of adding a validated screening tool to the STOP program's baseline questionnaire (19/23); however, following through with a brief intervention and referral to treatment proved challenging due to lack of training, limited time, and fear of stigmatizing patients. Practitioners in the intervention arm (5/11; 45%) might not follow the recommendations from CDSS if these recommendations are not perceived as beneficial to the patients. CONCLUSIONS: The results of the study show that practitioners' beliefs were reflective of the current social norms around alcohol use and this influenced their decision to offer a brief alcohol intervention. Future interventions need to emphasize both organizational and sociocultural factors as part of the design. The results of this study point to the need to change social norms regarding alcohol in order to effectively implement interventions that target both alcohol and tobacco use in primary care clinics. Trial registration ClinicalTrials.gov NCT03108144. Retrospectively registered 11 April 2017, https://www.clinicaltrials.gov/ct2/show/NCT03108144.

Predictors of premature treatment termination in a large residential addiction medicine program.

BACKGROUND: While inpatient programs are a common setting for addiction treatment, patients' premature termination is a major concern. Predicting premature treatment termination has the potential to substantially improve patient outcomes by identifying high-risk profiles and suggesting care paths that might reduce dropout. The current study examined the predictors of premature termination from an inpatient addiction medicine service. METHODS: In 1082 patients admitted to a large inpatient addiction medicine service, we used intake assessments of severity of alcohol use disorder, illicit drug use disorder, post-traumatic stress disorder (PTSD), anxiety disorders, and major depressive disorder to predict planned termination (n = 922) or premature termination (n = 160). We used two complementary analytic approaches-traditional binary logistic regression and a data-driven latent profile analysis (LPA). RESULTS: Binary logistic regression revealed that alcohol use severity, illicit drug use severity, and PTSD severity significantly predicted termination status, although alcohol use severity notably exhibited an inverse relationship. The LPA revealed four distinct profiles, with one profile exhibiting a significantly higher rate of premature termination and another exhibiting a significantly lower rate of premature termination. The high-risk profile was characterized by high drug severity, high comorbid psychopathology (PTSD, depression, and anxiety symptoms), but low alcohol severity. The low-risk profile was characterized by high alcohol severity, but low drug use and low comorbid psychopathology. CONCLUSIONS: These results provide converging evidence that illicit drug severity and psychiatric severity, and particularly PTSD, were associated with premature termination. Moreover, the LPA revealed distinct latent subgroups of patients with meaningfully higher and lower risk of premature termination, suggesting that addiction services should develop strategies for identifying high-risk individuals or develop care paths for high-risk symptom clusters. Approaches that are trauma-informed or otherwise focus on the management of comorbid psychiatric conditions may be particularly appropriate for reducing premature termination.

Personalized dosing of nicotine replacement therapy versus standard dosing for the treatment of individuals with tobacco dependence: study protocol for a randomized placebo-controlled trial.

BACKGROUND: Medications for smoking cessation are currently only effective in helping a minority of smokers quit. Drug development is slow and expensive; as such, there is much interest in optimizing the effectiveness of existing treatments and medications. Current standard doses of nicotine replacement therapy are not effective for many smokers, and in many cases, the amount of nicotine provided is much less than when a smoker is smoking their usual number of cigarettes. The proposed study will test if titrating the dose of the nicotine patch (up to 84 mg) will improve quitting success compared to those receiving a 21-mg nicotine patch with increasing doses of placebo patch. METHODS: This is a multicenter, pragmatic, two-arm, placebo-controlled, block randomized controlled trial. We will recruit participants who smoke at least 10 cigarettes daily and are interested in making a quit attempt. After 2 weeks of usual treatment with a 21-mg patch, participants who fail to quit smoking (target n = 400) will be randomized to receive escalating doses of a nicotine patch vs matching placebo patches for an additional 10 weeks or up to a maximum dose of 84 mg per day. Those who stop smoking during the first 2 weeks of usual treatment will continue with 21 mg patch treatment for 10 weeks and will form an additional comparison arm. In addition to the medication, participants will receive brief behavioral counseling at each study visit. The primary outcome will be biochemically confirmed continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9 to 12). DISCUSSION: Research evidence supporting the effectiveness of personalized doses of nicotine replacement therapy could change current practice in a variety of healthcare settings. Given the evidence that quitting smoking at any age diminishes the risk of tobacco-related morbidity and mortality, even small increases in absolute quit rates can have a substantial population-level impact on reducing smoking-related disease, mortality rates, and associated healthcare costs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03000387 . Registered on 22 December 2016.

Brief Interventions for Cannabis Use in Healthcare Settings: Systematic Review and Meta-analyses of Randomized Trials.

OBJECTIVES: The efficacy of brief interventions for cannabis use was assessed in a systematic review and meta-analyses. METHODS: Systematic searches in academic databases were conducted, and reference lists of included studies were reviewed. Randomized trials were included that compared brief interventions with minimal control interventions for improving cannabis-specific outcomes among participants recruited from healthcare settings. Mean differences (MDs) based on change-from-baseline measurements were pooled using random-effects meta-analyses, with stratification by short term (≤3 months) and long term (>3 months). RESULTS: Ten reports from 9 studies were included. Most studies were conducted in the United States, including participants who were adults and were recruited from primary care or emergency departments. There were no significant effects of brief interventions on cannabis-specific Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) scores in the short term (MD -1.27 points; 95% confidence interval [CI] -3.75, 1.21; I 84.40%). The null pattern of findings was also observed for number of days of cannabis use in the past 30 days in the short term (MD -0.22 days; 95% CI -2.27, 1.82; I 60.30%) and long term (MD -0.28 days; 95% CI -2.42, 1.86; I 60.50%). The evidence base for other outcomes not subjected to meta-analyses was limited and mixed. CONCLUSIONS: Brief interventions did not result in reductions in cannabis-specific ASSIST scores or number of days of cannabis use, whereas the evidence base for other outcomes was limited and mixed. As such, brief interventions in healthcare settings may not be efficacious for cannabis use.

The effect of a clinical decision support system on prompting an intervention for risky alcohol use in a primary care smoking cessation program: a cluster randomized trial.

BACKGROUND: Clinical decision support systems (CDSSs) may promote practitioner adherence to evidence-based guidelines. This study examined if the addition of a CDSS influenced practitioner delivery of a brief intervention with treatment-seeking smokers who were drinking above recommended alcohol consumption guidelines, compared with practitioners who do not receive a CDSS prompt. METHODS: This was a cluster randomized controlled trial conducted in primary health care clinics across Ontario, Canada, implementing the Smoking Treatment for Ontario Patients (STOP) smoking cessation program. Clinics randomized to the intervention group received a prompt when a patient reported consuming alcohol above the Canadian Cancer Society (CCS) guidelines; the control group did not receive computer alerts. The primary outcome was an offer of an appropriate educational alcohol resource, an alcohol reduction workbook for patients drinking above the CCS guidelines, and an abstinence workbook to patients scoring above 20 points in the AUDIT screening tool; the secondary outcome was patient acceptance of the resource. The tertiary outcome was patient abstinence from smoking, and alcohol consumption within CCS guidelines, at 6-month follow-up. Results were analyzed using a generalized estimation approach for fitting logistic regression using a population-averaged method. RESULTS: Two hundred and twenty-one clinics across Ontario were randomized for this study; 110 to the intervention arm and 111 to the control arm. From the 15,222 patients that enrolled in the smoking cessation program, 15,150 (99.6% of patients) were screened for alcohol use and 5715 patients were identified as drinking above the CCS guidelines. No statistically significant difference between groups was seen in practitioner offer of an educational alcohol resource to appropriate patients (OR = 1.19, 95% CI 0.88-1.64, p = 0.261) or in patient abstinence from smoking and drinking within the CCS guidelines at 6-month follow-up (OR = 0.93, 95% CI 0.71-1.22, p = 0.594). However, a significantly greater proportion of patients in the intervention group accepted the alcohol resource offered to them by their practitioner (OR = 1.48, 95% CI 1.01-2.16, p = 0.045). CONCLUSION: A CDSS may not increase the likelihood of practitioners offering an educational alcohol resource, though it may have influenced patients' acceptance of the resource. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT03108144 , registered on April 11, 2017, "retrospectively registered".

Trends in treatment of problematic cannabis use in Ontario's specialized addiction treatment system from 2010/11 to 2015/16: a repeated cross-sectional study of a health administrative database.

BACKGROUND: Little is known about trends in the treatment of problematic cannabis use in Canada. Trends in treatment utilization for problematic cannabis use were examined, as well as trends in the associated sociodemographic characteristics and frequency of cannabis use. METHODS: This was a repeated cross-sectional study using data from the Drug and Alcohol Treatment Information System, capturing utilization of all community funded addiction treatment services in Ontario, Canada. Clients in treatment for their own problematic cannabis use from 2010/11 to 2015/16 were included. Two distinct groups were formed: clients with problematic cannabis use only (the cannabis-only group) and clients with problematic use of cannabis and other substances (the cannabis-plus group). Estimates of the number of clients in each of these groups and their cannabis use frequency (past 30 days) were characterized over time by new admissions and total caseload (new admissions plus carryovers). RESULTS: There were 152 984 admissions for 83 621 clients over the study period. The number of clients with new admissions in the cannabis-only group decreased from 2954 (95% confidence interval [CI] 2848-3062) in 2010/11 to 2342 (95% CI 2248-2439) in 2015/16. Similar downward trends were observed in the number of clients in the total caseload of this group. The number of clients with new admissions in the cannabis-plus group was stable, but the total caseload increased from 20 139 clients (95% CI 19 862-20 419) in 2011/12 to 21 816 (95% CI 21 527-22 107) in 2015/16. Proportions of daily cannabis use increased among clients in both groups. INTERPRETATION: The number of clients in treatment for problematic cannabis use only decreased over the study period, but the frequency of cannabis use increased among clients in both groups. Given the potential reductions in treatment that is unnecessary from a clinical standpoint, alignment of treatment programming with disorder severity may be warranted.

Outcomes of an integrated care pathway for concurrent major depressive and alcohol use disorders: a multisite prospective cohort study.

BACKGROUND: In 2013, an Integrated Care Pathway (ICP) for concurrent Major Depressive (MDD) and Alcohol Use (AUD) Disorders was developed at the Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada. The ICP was further implemented at 8 other clinical sites across Ontario (the DA VINCI Project) in 2015-2017. The goal of this study was to systematically describe and analyze the main clinical outcomes of the project. METHODS: Data on a non-randomized cohort of patients receiving ICP-based treatment were collected prospectively at nine clinical sites in a variety of clinical settings. STATISTICAL METHODS: descriptive statistics, t-test, chi-square, ANOVA, generalized linear models. RESULTS: Two hundred forty-six patients were enrolled, 58.8% males, mean age was 45.6 years, 170 patients received treatment at academic health centres (AHC), 49 - at community hospitals (CH) and 27 - in family health teams (FHT). There were no major differences in anamnestic parameters and depression severity between the three settings, but there were differences in baseline drinking patterns between subgroups (F = 4.271, df = 2, p = 0.015). Overall completion rate was 70.7% with no significant variation between settings (χ2 = 3.35, df = 2, p = 0.19). Treatment duration in AHC was the longest, and completion rates were the highest. There was a statistically significant and clinically meaningful reduction in the number of drinking days per week (1.81, t = 8.78, p < 0.001). The cohort overall demonstrated significant and meaningful reduction in severity of cravings (Penn Alcohol Craving Scale: 4.42, t = 8.63, p < 0.001) and depressive symptoms (Quick Inventory of Depressive Symptomatology: 4.25, t = 11.26, p < 0.001). While some of the baseline patient characteristics and treatment parameters varied between the settings, the variation in clinical outcomes was mostly insignificant, though clinical improvement was more pronounced in academic setting and with individual therapy. CONCLUSIONS: The study demonstrated that ICP is a feasible and effective treatment for concurrent AUD and MDD that delivers meaningful clinical improvement in a variety of settings. A randomized controlled study is needed to properly compare the treatment outcomes between ICP model and treatment as usual and to further explore the role of various factors on treatment outcomes.

Management of mood and anxiety disorders in patients receiving opioid agonist therapy: Review and meta-analysis.

BACKGROUND AND OBJECTIVES: Patients with opioid use disorders and mood and anxiety symptoms have a variable prognosis. Few randomized controlled trials (RCTs) have evaluated treatment of depression or anxiety in patients receiving opioid agonist therapies (OAT). This review evaluates studies of pharmacotherapy/psychotherapy for treating symptoms of depression or anxiety in patients receiving OAT. METHODS: Public databases were searched for clinical trials of pharmacotherapy or psychotherapy for managing depression or anxiety symptoms in adults receiving OAT. Subsequently, we conducted a random effects meta-analysis model of RCTs by antidepressants subclasses. RESULTS: In our literature search, we identified 22 RCTs, eight of which were eligible for meta-analysis. Seven studies evaluated antidepressants in patients already maintained on OAT; two studies reported significant results for antidepressant effects versus placebo. Similarly, two of the seven studies that initiated antidepressants with OAT had advantages over placebo. Meta-analysis of grouped data revealed that tricyclic antidepressants (TCAs) (n = 235) significantly improved mean depression scores (SMD = -2.35, 95%CI: [-4.35, -0.34], z = -2.29, p = .022) while Selective Serotonin Reuptake Inhibitors (SSRIs) (n = 311) were not significantly different than placebo (SMD = 0.47, 95%CI: [-0.35, 1.30], z = 1.12, p = .263). Four out of five studies that implemented psychotherapeutic approaches reported a greater reduction of depressive symptoms than the comparison group. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: To date, psychotherapy has the most documented evidence for efficacy. TCAs appears effective but with more adverse effects than SSRIs. Further studies of OAT and adjunct antidepressant treatments for dual diagnosis patients are warranted. (Am J Addict 2017;26:551-563).

Alcohol consumption as a risk factor for tuberculosis: meta-analyses and burden of disease.

Meta-analyses of alcohol use, alcohol dosage and alcohol-related problems as risk factors for tuberculosis incidence were undertaken. The global alcohol-attributable tuberculosis burden of disease was also re-estimated.Systematic searches were conducted, reference lists were reviewed and expert consultations were held to identify studies. Cohort and case-control studies were included if there were no temporal violations of exposure and outcome. Risk relations (RRs) were pooled by using categorical and dose-response meta-analyses. The alcohol-attributable tuberculosis burden of disease was estimated by using alcohol-attributable fractions.36 of 1108 studies were included. RRs for alcohol use and alcohol-related problems were 1.35 (95% CI 1.09-1.68; I2: 83%) and 3.33 (95% CI 2.14-5.19; 87%), respectively. Concerning alcohol dosage, tuberculosis risk rose as ethanol intake increased, with evidence of a threshold effect. Alcohol consumption caused 22.02 incident cases (95% CI 19.70-40.77) and 2.35 deaths (95% CI 2.05-4.79) per 100 000 people from tuberculosis in 2014. Alcohol-attributable tuberculosis incidence increased between 2000 and 2014 in most high tuberculosis burden countries, whereas mortality decreased.Alcohol consumption was associated with an increased risk of tuberculosis in all meta-analyses. It was consequently a major contributor to the tuberculosis burden of disease.

Integrated care pathway for co-occurring major depressive and alcohol use disorders: Outcomes of the first two years.

BACKGROUND: Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are highly prevalent, comorbid, and have significant impact on morbidity, mortality, and socioeconomic burden in Canada. Combined psycho- and pharmacotherapies for both conditions promise better outcomes than treatment as usual (TAU). At the Centre for Addiction and Mental Health, Toronto, Canada, we developed and implemented an Integrated Care Pathway (ICP) specifically for treatment of concurrent MDD and AUD. The goal of the study is to assess the clinical effectiveness of the ICP approach in comparison to TAU. MATERIALS AND METHODS: Non-randomized design, clinical chart review, Chi-square and t-tests, Cohen's d, Linear Mixed Effects Models, Kaplan-Meier, and log-rank analyses. RESULTS: Eighty-one ICP patients were included, matched to 81 controls by age, sex, severity of depressive symptoms, and patterns of drinking. ICP cohort had a significantly lower dropout rate (18.5% vs 69.1%, p < .001; at 16 weeks of treatment, respectively), both cohorts demonstrated significant reduction in the number of heavy drinking days (ß = .01, p < .001) and standard drinks per week (ß = .15, p < .001) with a significantly higher reduction of both indicators over time in the ICP cohort. Significant reduction in depressive symptoms severity (QIDS: 14.6 vs 10.0, p < .001; BDI: 26.3 vs 16.2, p < .001) was observed in ICP cohort (no data for TAU cohort). CONCLUSIONS: The ICP patients demonstrated improvements on several levels including depressive symptoms, and changes in alcohol drinking patterns. The study demonstrated the overall effectiveness of the ICP and apparent advantage over TAU, which must be corroborated through a randomized clinical trial. (Am J Addict 2017;26:602-609) SCIENTIFIC SIGNIFICANCE: This study is one of the first works showing the outcomes of an ICP developed in the mental health area and for co-occurring disorders. Despite the limitations, the relative advantage of the ICP methodology warrants future research in this area.

The relationship between different dimensions of alcohol use and the burden of disease-an update.

BACKGROUND AND AIMS: Alcohol use is a major contributor to injuries, mortality and the burden of disease. This review updates knowledge on risk relations between dimensions of alcohol use and health outcomes to be used in global and national Comparative Risk Assessments (CRAs). METHODS: Systematic review of reviews and meta-analyses on alcohol consumption and health outcomes attributable to alcohol use. For dimensions of exposure: volume of alcohol use, blood alcohol concentration and patterns of drinking, in particular heavy drinking occasions were studied. For liver cirrhosis, quality of alcohol was additionally considered. For all outcomes (mortality and/or morbidity): cause of death and disease/injury categories based on International Classification of Diseases (ICD) codes used in global CRAs; harm to others. RESULTS: In total, 255 reviews and meta-analyses were identified. Alcohol use was found to be linked causally to many disease and injury categories, with more than 40 ICD-10 three-digit categories being fully attributable to alcohol. Most partially attributable disease categories showed monotonic relationships with volume of alcohol use: the more alcohol consumed, the higher the risk of disease or death. Exceptions were ischaemic diseases and diabetes, with curvilinear relationships, and with beneficial effects of light to moderate drinking in people without heavy irregular drinking occasions. Biological pathways suggest an impact of heavy drinking occasions on additional diseases; however, the lack of medical epidemiological studies measuring this dimension of alcohol use precluded an in-depth analysis. For injuries, except suicide, blood alcohol concentration was the most important dimension of alcohol use. Alcohol use caused marked harm to others, which has not yet been researched sufficiently. CONCLUSIONS: Research since 2010 confirms the importance of alcohol use as a risk factor for disease and injuries; for some health outcomes, more than one dimension of use needs to be considered. Epidemiological studies should include measurement of heavy drinking occasions in line with biological knowledge.

Effects of naltrexone on alcohol self-administration and craving: meta-analysis of human laboratory studies.

Randomized clinical trials have established the efficacy of naltrexone for reducing quantity of alcohol consumption and incidence of relapse to heavy drinking. To evaluate putative treatment mechanisms, human laboratory studies have examined naltrexone's effects on alcohol responses and self-administration during short-term medication protocols. Results from these studies are inconsistent and have yet to be examined in aggregate. This meta-analysis aimed to quantify naltrexone's effects on alcohol self-administration and craving in the context of placebo-controlled human laboratory trials. Potential moderators of medication effects were also examined. Meta-analyses of alcohol self-administration (k = 9, N = 490) and craving (k = 16, N = 748) confirmed that, under controlled experimental conditions, naltrexone reduces the quantity of consumption (Hedges' g = -.277, SE = .074, 95 percent CI = -.421, -.133, p < .001) and magnitude of self-reported craving (g = -.286, SE = .066, 95 percent CI = -.416, -.156, p < .001) relative to placebo. Subgroup and moderation analyses found no evidence that effect sizes differed by study population (dependent versus non-dependent drinkers), laboratory paradigm or duration of medication exposure. These results substantiate prior evidence for reductions in event-level craving and consumption as potential treatment mediators, also establishing effect sizes to inform future human laboratory trials. From a clinical perspective, these results may provide additional evidence regarding naltrexone's efficacy in the context of acute or subacute dosing regimens.

Opioid-induced constipation reversal in response to placebo in a patient with a history of IBS receiving methadone maintenance therapy.

Opioid-induced constipation (OIC) is one of the major side effects in patients receiving methadone maintenance treatment (MMT). Quite often, constipation becomes a factor significantly affecting therapeutic options and choices. Currently used approaches are symptomatic and in many cases ineffective. At the same time, it is well known that the gastrointestinal system is a subject for psychosomatic influences. In this case report, we describe an unexpected outcome of placebo administration in a patient suffering from OIC since her participation in MMT. The patient participated in a triple-blind randomised placebo-controlled trial of naloxone for treatment of OIC. As part of the study crossover design, the patient received 1 week of placebo followed by 1 week of naloxone, and had significant improvement in her bowel functioning when receiving placebo, then returned to baseline during the second week of the study.

Development and Implementation of an Ambulatory Integrated Care Pathway for Major Depressive Disorder and Alcohol Dependence.

Integrated care pathways (ICPs) provide an approach for delivering evidence-based treatment in a hospital setting. This column describes the development and pilot implementation in a clinical setting of an ICP for patients with concurrent major depressive disorder and alcohol dependence at the Centre for Addiction and Mental Health (CAMH), an academic tertiary care hospital, in Toronto, Canada. The ICP methodology includes evidence reviews, knowledge translation, process reengineering, and change management. Pilot results indicate high patient satisfaction, evidence of symptom improvement, and excellent retention.

Alcohol Consumption as a Risk Factor for Acute and Chronic Pancreatitis: A Systematic Review and a Series of Meta-analyses.

BACKGROUND: Pancreatitis is a highly prevalent medical condition associated with a spectrum of endocrine and exocrine pancreatic insufficiencies. While high alcohol consumption is an established risk factor for pancreatitis, its relationship with specific types of pancreatitis and a potential threshold have not been systematically examined. METHODS: We conducted a systematic literature search for studies on the association between alcohol consumption and pancreatitis based on PRISMA guidelines. Non-linear and linear random-effect dose-response meta-analyses using restricted cubic spline meta-regressions and categorical meta-analyses in relation to abstainers were conducted. FINDINGS: Seven studies with 157,026 participants and 3618 cases of pancreatitis were included into analyses. The dose-response relationship between average volume of alcohol consumption and risk of pancreatitis was monotonic with no evidence of non-linearity for chronic pancreatitis (CP) for both sexes (p = 0.091) and acute pancreatitis (AP) in men (p = 0.396); it was non-linear for AP in women (p = 0.008). Compared to abstention, there was a significant decrease in risk (RR = 0.76, 95%CI: 0.60-0.97) of AP in women below the threshold of 40 g/day. No such association was found in men (RR = 1.1, 95%CI: 0.69-1.74). The RR for CP at 100 g/day was 6.29 (95%CI: 3.04-13.02). INTERPRETATION: The dose-response relationships between alcohol consumption and risk of pancreatitis were monotonic for CP and AP in men, and non-linear for AP in women. Alcohol consumption below 40 g/day was associated with reduced risk of AP in women. Alcohol consumption beyond this level was increasingly detrimental for any type of pancreatitis. FUNDING: The work was financially supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (R21AA023521) to the last author.