Impact of alcohol on the progression of HCV-related liver disease: A systematic review and meta-analysis.

BACKGROUND & AIMS: Despite a marked reduction in new cases of cirrhosis caused by HCV infection, over 500,000 new cirrhosis cases in this category were estimated globally in 2019. This contribution quantifies the relationship between alcohol use and the progression of liver disease in people with HCV infections. METHODS: The causal impact of different levels of alcohol use on cirrhosis has previously been established. The quantification of this relationship was undertaken based on a systematic search of the literature and a meta-analysis. We limited our search to longitudinal and case-control studies with biologically verified outcomes. Different sensitivity analyses were conducted to check on key assumptions and on the generalizability of the relationship. RESULTS: Alcohol use has a dose-dependent relationship with incident cirrhosis, which is linear on the log-linear level, and thus exponential on the level of odds ratios or other risk indicators. Each standard drink of 12 grams of pure alcohol per day increases the risk by about 11%. The results were stable regardless of the statistical model used, level of adjustment, quality of the study, or outcome (i.e., cirrhosis, decompensated cirrhosis, liver-related death). CONCLUSIONS: Alcohol use has a marked impact on the progression of HCV infections to cirrhosis and more severe liver outcomes. LAY SUMMARY: Alcohol consumption has a significant impact on the progression of liver disease in people with HCV infections. Each alcoholic drink per day is associated with an increase in the risk of cirrhosis of 11%.

Global alcohol exposure between 1990 and 2017 and forecasts until 2030: a modelling study.

BACKGROUND: Alcohol use is a leading risk factor for global disease burden, and data on alcohol exposure are crucial to evaluate progress in achieving global non-communicable disease goals. We present estimates on the main indicators of alcohol exposure for 189 countries from 1990-2017, with forecasts up to 2030. METHODS: Adult alcohol per-capita consumption (the consumption in L of pure alcohol per adult [≥15 years]) in a given year was based on country-validated data up to 2016. Forecasts up to 2030 were obtained from multivariate log-normal mixture Poisson distribution models. Using survey data from 149 countries, prevalence of lifetime abstinence and current drinking was obtained from Dirichlet regressions. The prevalence of heavy episodic drinking (30-day prevalence of at least one occasion of 60 g of pure alcohol intake among current drinkers) was estimated with fractional response regressions using survey data from 118 countries. FINDINGS: Between 1990 and 2017, global adult per-capita consumption increased from 5·9 L (95% CI 5·8-6·1) to 6·5 L (6·0-6·9), and is forecasted to reach 7·6 L (6·5-10·2) by 2030. Globally, the prevalence of lifetime abstinence decreased from 46% (42-49) in 1990 to 43% (40-46) in 2017, albeit this was not a significant reduction, while the prevalence of current drinking increased from 45% (41-48) in 1990 to 47% (44-50) in 2017. We forecast both trends to continue, with abstinence decreasing to 40% (37-44) by 2030 (annualised 0·2% decrease) and the proportion of current drinkers increasing to 50% (46-53) by 2030 (annualised 0·2% increase). In 2017, 20% (17-24) of adults were heavy episodic drinkers (compared with 1990 when it was estimated at 18·5% [15·3-21·6%], and this prevalence is expected to increase to 23% (19-27) in 2030. INTERPRETATION: Based on these data, global goals for reducing the harmful use of alcohol are unlikely to be achieved, and known effective and cost-effective policy measures should be implemented to reduce alcohol exposure. FUNDING: Centre for Addiction and Mental Health and the WHO Collaborating Center for Addiction and Mental Health at the Centre for Addiction and Mental Health.

Alcohol Consumption and Risk of Liver Cirrhosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically summarize the risk relationship between different levels of alcohol consumption and incidence of liver cirrhosis. METHODS: MEDLINE and Embase were searched up to March 6, 2019, to identify case-control and cohort studies with sex-specific results and more than 2 categories of drinking in relation to the incidence of liver cirrhosis. Study characteristics were extracted and random-effects meta-analyses and meta-regressions were conducted. RESULTS: A total of 7 cohort studies and 2 case-control studies met the inclusion criteria, providing data from 2,629,272 participants with 5,505 cases of liver cirrhosis. There was no increased risk for occasional drinkers. Consumption of one drink per day in comparison to long-term abstainers showed an increased risk for liver cirrhosis in women, but not in men. The risk for women was consistently higher compared to men. Drinking ≥5 drinks per day was associated with a substantially increased risk in both women (relative risk [RR] = 12.44, 95% confidence interval [CI]: 6.65-23.27 for 5-6 drinks, and RR = 24.58, 95% CI: 14.77-40.90 for ≥7 drinks) and men (RR = 3.80, 95% CI: 0.85-17.02, and RR = 6.93, 95% CI: 1.07-44.99, respectively). Heterogeneity across studies indicated an additional impact of other risk factors. DISCUSSION: Alcohol is a major risk factor for liver cirrhosis with risk increasing exponentially. Women may be at higher risk compared to men even with little alcohol consumption. More high-quality research is necessary to elucidate the role of other risk factors, such as genetic vulnerability, body weight, metabolic risk factors, and drinking patterns over the life course. High alcohol consumption should be avoided, and people drinking at high levels should receive interventions to reduce their intake.

Cannabis and Driving in Older Adults.

Importance: Epidemiological studies have found that cannabis increases the risk of a motor vehicle collision. Cannabis use is increasing in older adults, but laboratory studies of the association between cannabis and driving in people aged older than 65 years are lacking. Objective: To investigate the association between cannabis, simulated driving, and concurrent blood tetrahydrocannabinol (THC) levels in older adults. Design, Setting, and Participants: Using an ecologically valid counterbalanced design, in this cohort study, regular cannabis users operated a driving simulator before, 30 minutes after, and 180 minutes after smoking their preferred legal cannabis or after resting. This study was conducted in Toronto, Canada, between March and November 2022 with no follow-up period. Data were analyzed from December 2022 to February 2023. Exposures: Most participants chose THC-dominant cannabis with a mean (SD) content of 18.74% (6.12%) THC and 1.46% (3.37%) cannabidiol (CBD). Main outcomes and measures: The primary end point was SD of lateral position (SDLP, or weaving). Secondary outcomes were mean speed (MS), maximum speed, SD of speed, and reaction time. Driving was assessed under both single-task and dual-task (distracted) conditions. Blood THC and metabolites of THC and CBD were also measured at the time of the drives. Results: A total of 31 participants (21 male [68%]; 29 White [94%], 1 Latin American [3%], and 1 mixed race [3%]; mean [SD] age, 68.7 [3.5] years), completed all study procedures. SDLP was increased and MS was decreased at 30 but not 180 minutes after smoking cannabis compared with the control condition in both the single-task (SDLP effect size [ES], 0.30; b = 1.65; 95% CI, 0.37 to 2.93; MS ES, -0.58; b = -2.46; 95% CI, -3.56 to -1.36) and dual-task (SDLP ES, 0.27; b = 1.75; 95% CI, 0.21 to 3.28; MS ES, -0.47; b = -3.15; 95% CI, -5.05 to -1.24) conditions. Blood THC levels were significantly increased at 30 minutes but not 180 minutes. Blood THC was not correlated with SDLP or MS at 30 minutes, and SDLP was not correlated with MS. Subjective ratings remained elevated for 5 hours and participants reported that they were less willing to drive at 3 hours after smoking. Conclusions and relevance: In this cohort study, the findings suggested that older drivers should exercise caution after smoking cannabis.

A systematic review on the impact of alcohol use on sexually transmitted infections.

Alcohol use has been associated with multiple types of sexual risk behaviors, such as condomless sex or having multiple sexual partners, behaviors that are linked to the risk of sexually transmitted infections (STIs). The aim of this review was to present updated evidence to demonstrate an association between alcohol consumption and STIs and evaluate the causal nature of this link, as well as to present interventions that reduce alcohol consumption and its effect on STIs. We conducted a systematic review according to the PRISMA guidelines using PubMed and Embase databases. Cohort studies and case-control studies were included. Any level of alcohol use served as the exposure variable, with the outcome restricted to non-HIV STIs, as reviews on alcohol use and HIV already exist. In total, 11 publications satisfied the inclusion criteria. The evidence suggests that there is an association between alcohol use, especially heavy drinking occasions, and STIs, with eight articles finding a statistically significant association. In addition to these results, there is indirect causal evidence from policy studies, and from the field of decision-making and sexual behavior with experimental evidence, that alcohol use increases the likelihood of risk-taking sexual behavior. It is important to have a deeper understanding of the association to develop effective prevention programs at community and individual levels. Preventive interventions should be implemented targeting the general population, in addition to specific campaigns directed at vulnerable subpopulations in order to reduce the risks.

The Utility of THC Cutoff Levels in Blood and Saliva for Detection of Impaired Driving.

Background: Δ9-Tetrahydrocannabinol (THC) is the psychoactive component in cannabis and a relationship of THC to driving impairment is expected. Despite this, there are discrepant findings with respect to the relationship of blood THC to driving. This study investigated the relationship of blood, urine, and saliva THC/THC-COOH levels to "weaving," as measured by a driving simulator. Methods: Participants smoked cannabis alone or with alcohol. THC/THC-COOH levels in blood, urine, and saliva were correlated with standard deviation of lateral position (SDLP), measuring "weaving." In addition, SDLP after cannabis and/or alcohol were compared with SDLP after placebo when THC/THC-COOH levels were above or below specified thresholds in blood (5 ng/mL), urine (50 ng/mL), or saliva (25 ng/mL). Results: A clear linear relationship between blood THC concentration and SDLP was not observed based on calculation of Spearman coefficients. When compared with placebo, SDLP was significantly increased after cannabis and cannabis combined with alcohol when THC in the blood was above the legal limit. SDLP was increased in drug conditions when saliva cutoffs were above the legal limit. Conclusions: The findings of this study suggest that specified thresholds for THC in blood and saliva may be able to detect driving impairment, but future studies are needed. ClinicalTrials.gov ID: NCT03106363.

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.

Is burden of disease differentially linked to spirits? A systematic scoping review and implications for alcohol policy.

Most epidemiological research on alcohol as a risk factor is based on the assumption that outcomes are linked to pattern and level of alcohol exposure, where different beverages are converted into grams of ethanol. This review examines this basic assumption, that alcohol has the same impact, independent of beverage type. We conducted a systematic search on comparative research of beverage-specific alcohol exposure and consequences. Research was divided by methodology (survey, case-control, cohort, time-series analyses, interventional research). Overall, many studies showed higher risks for spirits compared to beer or wine; however, most research was not controlled adequately for confounders such as patterns of drinking. While there is no conclusive evidence for spirits being associated with more harm, given the same pattern and level of alcohol exposure, some evidence supports for certain outcomes such as injuries and poisonings, a potential excess risk with spirits consumption due to rapid ethanol intake and intoxication. Accordingly, encouraging people to opt for beverages with lower alcohol content via taxation strategies has the potential to reduce alcohol-attributable harm. This does not necessarily involve switching beverage type, but also can achieved within the same beverage category, by shifting from higher to lower concentration beverages.

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.

Alcohol use and dementia: a systematic scoping review.

BACKGROUND: Alcohol use has been identified as a risk factor for dementia and cognitive decline. However, some patterns of drinking have been associated with beneficial effects. METHODS AND RESULTS: To clarify the relationship between alcohol use and dementia, we conducted a scoping review based on a systematic search of systematic reviews published from January 2000 to October 2017 by using Medline, Embase, and PsycINFO. Overall, 28 systematic reviews were identified: 20 on the associations between the level of alcohol use and the incidence of cognitive impairment/dementia, six on the associations between dimensions of alcohol use and specific brain functions, and two on induced dementias. Although causality could not be established, light to moderate alcohol use in middle to late adulthood was associated with a decreased risk of cognitive impairment and dementia. Heavy alcohol use was associated with changes in brain structures, cognitive impairments, and an increased risk of all types of dementia. CONCLUSION: Reducing heavy alcohol use may be an effective dementia prevention strategy.

Regulatory Policies for Alcohol, other Psychoactive Substances and Addictive Behaviours: The Role of Level of Use and Potency. A Systematic Review.

The object of this contribution based on a systematic review of the literature is to examine to what degree the level of use and potency play a role in regulatory policies for alcohol, other psychoactive substances and gambling, and whether there is an evidence base for this role. Level of use is usually defined around a behavioural pattern of the user (for example, cigarettes smoked per day, or average ethanol use in grams per day), while potency is defined as a property or characteristic of the substance. For all substances examined (alcohol, tobacco, opioids, cannabis) and gambling, both dimensions were taken into consideration in the formulation of most regulatory policies. However, the associations between both dimensions and regulatory policies were not systematic, and not always based on evidence. Future improvements are suggested.

Contribution of alcohol use disorders to the burden of dementia in France 2008-13: a nationwide retrospective cohort study.

BACKGROUND: Dementia is a prevalent condition, affecting 5-7% of people aged 60 years and older, and a leading cause of disability in people aged 60 years and older globally. We aimed to examine the association between alcohol use disorders and dementia risk, with an emphasis on early-onset dementia (<65 years). METHODS: We analysed a nationwide retrospective cohort of all adult (≥20 years) patients admitted to hospital in metropolitan France between 2008 and 2013. The primary exposure was alcohol use disorders and the main outcome was dementia, both defined by International Classification of Diseases, tenth revision discharge diagnosis codes. Characteristics of early-onset dementia were studied among prevalent cases in 2008-13. Associations of alcohol use disorders and other risk factors with dementia onset were analysed in multivariate Cox models among patients admitted to hospital in 2011-13 with no record of dementia in 2008-10. FINDINGS: Of 31 624 156 adults discharged from French hospitals between 2008 and 2013, 1 109 343 were diagnosed with dementia and were included in the analyses. Of the 57 353 (5·2%) cases of early-onset dementia, most were either alcohol-related by definition (22 338 [38·9%]) or had an additional diagnosis of alcohol use disorders (10 115 [17·6%]). Alcohol use disorders were the strongest modifiable risk factor for dementia onset, with an adjusted hazard ratio of 3·34 (95% CI 3·28-3·41) for women and 3·36 (3·31-3·41) for men. Alcohol use disorders remained associated with dementia onset for both sexes (adjusted hazard ratios >1·7) in sensitivity analyses on dementia case definition (including Alzheimer's disease) or older study populations. Also, alcohol use disorders were significantly associated with all other risk factors for dementia onset (all p<0·0001). INTERPRETATION: Alcohol use disorders were a major risk factor for onset of all types of dementia, and especially early-onset dementia. Thus, screening for heavy drinking should be part of regular medical care, with intervention or treatment being offered when necessary. Additionally, other alcohol policies should be considered to reduce heavy drinking in the general population. FUNDING: None.

Sex-Specific Associations Between Alcohol Consumption and Incidence of Hypertension: A Systematic Review and Meta-Analysis of Cohort Studies.

BACKGROUND: Although it is well established that heavy alcohol consumption increases the risk of hypertension, the risk associated with low levels of alcohol intake in men and women is unclear. METHODS AND RESULTS: We searched Medline and Embase for original cohort studies on the association between average alcohol consumption and incidence of hypertension in people without hypertension. Random-effects meta-analyses and metaregressions were conducted. Data from 20 articles with 361 254 participants (125 907 men and 235 347 women) and 90 160 incident cases of hypertension (32 426 men and 57 734 women) were included. In people drinking 1 to 2 drinks/day (12 g of pure ethanol per drink), incidence of hypertension differed between men and women (relative riskwomen vs men=0.79; 95% confidence interval, 0.67-0.93). In men, the risk for hypertension in comparison with abstainers was relative risk=1.19 (1.07-1.31; I2=59%), 1.51 (1.30-1.76), and 1.74 (1.35-2.24) for consumption of 1 to 2, 3 to 4, and 5 or more standard drinks per day, respectively. In women, there was no increased risk for 1 to 2 drinks/day (relative risk=0.94; 0.88-1.01; I2=73%), and an increased risk for consumption beyond this level (relative risk=1.42; 1.22-1.66). CONCLUSIONS: Any alcohol consumption was associated with an increase in the risk for hypertension in men. In women, there was no risk increase for consumption of 1 to 2 drinks/day and an increased risk for higher consumption levels. We did not find evidence for a protective effect of alcohol consumption in women, contrary to earlier meta-analyses.

The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis.

BACKGROUND: Although it is well established that heavy alcohol consumption increases the risk of hypertension, little is known about the effect of a reduction of alcohol intake on blood pressure. We aimed to assess the effect of a reduction in alcohol consumption on change in blood pressure stratified by initial amount of alcohol consumption and sex in adults. METHODS: In this systematic review and meta-analysis, we searched MedLine, Embase, CENTRAL, and ClinicalTrials.gov from database inception up to July 13, 2016, for trials investigating the effect of a change of alcohol consumption on blood pressure in adults using keywords and MeSH terms related to alcohol consumption, blood pressure, and clinical trials, with no language restrictions. We also searched reference lists of identified articles and published meta-analyses and reviews. We included full-text articles with original human trial data for the effect of a change of alcohol consumption on blood pressure in adults, which reported a quantifiable change in average alcohol consumption that lasted at least 7 days and a corresponding change in blood pressure. We extracted data from published reports. We did random-effects meta-analyses stratified by amount of alcohol intake at baseline. All meta-analyses were done with Stata (version 14.1). For the UK, we modelled the effect of a reduction of alcohol consumption for 50% of the population drinking more than two standard drinks per day (ie, 12 g pure alcohol per drink). FINDINGS: 36 trials with 2865 participants (2464 men and 401 women) were included. In people who drank two or fewer drinks per day, a reduction in alcohol was not associated with a significant reduction in blood pressure; however, in people who drank more than two drinks per day, a reduction in alcohol intake was associated with increased blood pressure reduction. Reduction in systolic blood pressure (mean difference -5·50 mm Hg, 95% CI -6·70 to -4·30) and diastolic blood pressure (-3·97, -4·70 to -3·25) was strongest in participants who drank six or more drinks per day if they reduced their intake by about 50%. For the UK, the results would translate into more than 7000 inpatient hospitalisations and 678 cardiovascular deaths prevented every year. INTERPRETATION: Reducing alcohol intake lowers blood pressure in a dose-dependent manner with an apparent threshold effect. Implementation of effective alcohol interventions in people who drink more than two drinks per day would reduce the disease burden from both alcohol consumption and hypertension, and should be prioritised in countries with substantial alcohol-attributable risk. FUNDING: National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health (NIH).

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.