Search

Background: Cas12a (formerly known as Cpf1), the class II type V CRISPR nuclease, has been widely used for genome editing in mammalian cells and plants due to its distinct characteristics from Cas9. Despite being one of the most robust Cas12a nucleases, LbCas12a in general is less efficient than SpCas9 for genome editing in human cells, animals, and plants., Results: To improve the editing efficiency of LbCas12a, we conduct saturation mutagenesis in E. coli and identify 1977 positive point mutations of LbCas12a. We selectively assess the editing efficiency of 56 LbCas12a variants in human cells, identifying an optimal LbCas12a variant (RVQ: G146R/R182V/E795Q) with the most robust editing activity. We further test LbCas12a-RV, LbCas12a-RRV, and LbCas12a-RVQ in plants and find LbCas12a-RV has robust editing activity in rice and tomato protoplasts. Interestingly, LbCas12a-RRV, resulting from the stacking of RV and D156R, displays improved editing efficiency in stably transformed rice and poplar plants, leading to up to 100% editing efficiency in T 0 plants of both plant species. Moreover, this high-efficiency editing occurs even at the non-canonical TTV PAM sites., Conclusions: Our results demonstrate that LbCas12a-RVQ is a powerful tool for genome editing in human cells while LbCas12a-RRV confers robust genome editing in plants. Our study reveals the tremendous potential of these LbCas12a variants for advancing precision genome editing applications across a wide range of organisms., (© 2023. The Author(s).)

Background: High-risk alcohol use is an established modifiable risk factor for dementia. However, prior reviews have not addressed sex differences in alcohol-related dementia risk. In this systematic review, we take a sex-specific perspective towards the alcohol-dementia link, taking into account the age of dementia onset., Methods: We searched electronic databases for original cohort or case-control studies investigating the association between alcohol use and dementia. Two restrictions were considered: First, studies had to report results stratified by sex. Second, given the fact that the age at dementia onset seems to affect the alcohol-dementia link, studies were required to distinguish between early-onset and late-onset dementia (cut-off: 65 years). Additionally, the contribution of alcohol to dementia incidence was quantified for a set of 33 European countries for the year 2019., Results: We reviewed 3,157 reports, of which 7 publications were finally included and summarised narratively. A lower dementia risk when drinking alcohol infrequent or at moderate levels was found in men (three studies) and women (four studies). High-risk use and alcohol use disorders increased the risk of mild cognitive impairment and dementia, particularly early-onset dementia. Estimating the alcohol-attributable share of incident dementia cases revealed that 3.2% and 7.8% of incident dementia cases were estimated to be attributable to high-risk alcohol use (at least 24 g of pure alcohol per day) in 45-to-64-year-old women and men, respectively., Conclusions: Research to date has paid little attention to the sex-specific link of alcohol and dementia. In the absence of sex-specific research, the established recommendations on high-risk alcohol use should be employed to communicate the alcohol-attributable dementia risk., (© 2023. The Author(s).)

As synthetic biology becomes increasingly capable and accessible, it is likewise increasingly critical to be able to make accurate biosecurity determinations regarding the pathogenicity or toxicity of particular nucleic acid or amino acid sequences. At present, this is typically done using the BLAST algorithm to determine the best match with sequences in the NCBI nucleic acid and protein databases. Neither BLAST nor any of the NCBI databases, however, are actually designed for biosafety determination. Critically, taxonomic errors or ambiguities in the NCBI nucleic acid and protein databases can also cause errors in BLAST-based taxonomic categorization. With heavily studied taxa and frequently used biotechnology tools, even low frequency taxonomic categorization issues can lead to high rates of errors in biosecurity decision-making. Here we focus on the implications for false positives, finding that BLAST against NCBI's protein database will now incorrectly categorize a number of commonly used biotechnology tool sequences as the pathogens or toxins with which they have been used. Paradoxically, this implies that problems are expected to be most acute for the pathogens and toxins of highest interest and for the most widely used biotechnology tools. We thus conclude that biosecurity tools should shift away from BLAST against general purpose databases and towards new methods that are specifically tailored for biosafety purposes., (© 2023. The Author(s).)

Objective: It is reasonable to believe that the alcohol policy environment can impact the suicide mortality rates in a given country, considering the well-known link between alcohol use and death by suicide. The current literature, albeit limited, suggests that an increase in alcohol taxation may result in a decrease in deaths by suicide and that the effect is sex-specific. Therefore, the objective of the current study was to test the impact of three alcohol control policy enactments (in 2008, 2017 and 2018) on suicide mortality among adults 25-74 years of age in Lithuania, by sex., Methods: To estimate the unique impact of three alcohol control policies, we conducted interrupted time-series analyses by employing a generalized additive mixed model on monthly sex-specific age-standardized suicide mortality rates from January 2001 to December 2018., Results: Analyses showed a significant impact of the 2017 ( p  = 0.016) alcohol control policy on suicide mortality for men only. Specifically, we estimated that in the year following the 2017 policy enactment, approximately 57 (95% CI: 9-107) deaths by suicide were prevented among men, 25-74 years of age. The three policy enactments tested were not found to significantly impact the suicide mortality rate among women., Conclusion: Alcohol control policies involving pricing, which result in a notable decrease in alcohol affordability, could be a cost-effective indirect suicide prevention mechanism in not only countries of the former Soviet Union, but in other high-income countries with a comparable health care system to that in Lithuania. HIGHLIGHTSIncreasing excise tax on alcohol was found to have a sex-specific impact on suicide mortalityThe 2017 alcohol policy prevented 57 deaths by suicide among men, 25-74 years of age, in the following yearAlcohol pricing policies may be a cost-effective indirect suicide prevention mechanism.

Introduction: Alcohol screening, brief advice and referral to treatment (SBIRT) in primary health care is an effective strategy to decrease alcohol consumption at population level. However, there is relatively scarce evidence regarding its economic returns in non-high-income countries. The current paper aims to estimate the return-on-investment of implementing a SBIRT program in Mexican primary health-care settings., Methods: Empirical data was collected in a quasi-experimental study, from 17 primary health-care centres in Mexico City regarding alcohol screening delivered by 145 health-care providers. This data was combined with data from a simulation study for a period of 10 years (2008 to 2017). Economic investments were calculated from a public sector health-care perspective as clinical consultation costs (salary and material costs) and program costs (set-up, adaptation, implementation strategies). Economic return was calculated as monetary gains in the public sector health-care, estimated via simulated reductions in alcohol consumption, dependent on population coverage of alcohol interventions delivered to primary health-care patients., Results: Results showed that scaling up a SBIRT program in Mexico over a 10-year period would lead to positive return-on-investment values ranging between 21% in scenario 4 (confidence interval -8.6%, 79.5%) and 110% in scenario 5 (confidence interval 51.5%, 239.8%). Moreover, over the 10-year period, up to 16,000 alcohol-related deaths could be avoided as a result of implementing the program., Discussion and Conclusions: SBIRT implemented at national level in Mexico may lead to substantial financial gains from a public sector health-care perspective., (© 2023 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Introduction: The COVID-19 pandemic may have led to an increase in the alcohol-specific mortality. Against this backdrop, the aim of this report is to explore alcohol-specific mortality trends in Germany of the years 2010 to 2020., Method: Alcohol-specific mortality data aggregated by sex, 5-year age groups and state were collected from the annual cause-of-death statistics and analysed descriptively by visual inspection., Results: The overall alcohol-specific mortality rate (age-standardised) has mainly decreased between 2010 and 2020. However, increased alcohol-specific mortality rates for the year 2020 compared to 2019 were found for both, women (+4.8%) and men (+5.5%), particularly in age groups between 40 and 69 years. Changes in alcohol-specific mortality rates differed between federated states, with steeper increases in East Germany., Discussion and Conclusions: Different mechanisms related to the increase in alcohol consumption, particularly among high-risk drinkers, and reduced resources in health care may have led to an increase in alcohol-specific mortality in Germany in 2020. Despite the recent decline in the alcohol-specific mortality in Germany, an increase in the death toll was observed in 2020., (© 2022 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Aims: The study's aim is to identify and classify the most important alcohol control policies in the Baltic countries (Estonia, Latvia and Lithuania) and Poland between 2000 and 2020., Methods: Policy analysis of Baltic countries and Poland, predicting potential policy impact on alcohol consumption, all-cause mortality and alcohol-attributable hospitalizations was discussed., Results: All Baltic countries implemented stringent availability restrictions on off-premises trading hours and different degrees of taxation increases to reduce the affordability of alcoholic beverages, as well as various degrees of bans on alcohol marketing. In contrast, Poland implemented few excise taxation increases or availability restrictions and, in fact, reduced stipulations on prior marketing bans., Conclusions: This classification of alcohol control policies in the Baltic countries and Poland provides a basis for future modeling of the impact of implementing effective alcohol control policies (Baltic countries), as well as the effects of loosening such policies (Poland)., (© 2022 Society for the Study of Addiction.)

In this work, reduction of alcoholic strength was discussed as a means to reduce consumption and alcohol-attributable harm. Statistical modelling was conducted to (1) estimate its potential for the largest six Western and Central European countries (France, Germany, Italy, Poland, Spain, UK); (2) calculate the increase in taxation necessary to reach this potential, and (3) estimate the mortality gains achieved with the introduction of no- or low-alcohol beverages in the UK and Spain. The high public health potential of reducing alcoholic strength was demonstrated via modelling a scenario in which the strength of all beverages was reduced by 10%, which would avert thousands of deaths in these six European countries per year. However, methods by which to achieve these gains were not clear, as the alcohol industry has shown no inclination toward reductions in the alcoholic strength of beer, wine, or spirits via a reformulation on a large scale. The increase of excise taxation to achieve the public health gains of such a reduction would result in markedly increasing prices-a situation unlikely to be implemented in Europe. Finally, the introduction of beer and wine with an alcoholic strength below 0.5% led to some substitutions of higher-strength beverages, but did not show a marked public health impact. New taxation initiatives to achieve the potential of a reduction of alcoholic strength will need to be implemented.

Background: In Germany, most individuals with alcohol dependence are recognized by the health care system and about 16% per year receive addiction-specific care. This paper aimed to analyze the prevalence and treatment utilization rate of people with alcohol dependence by type of addiction-specific care in the federal state of Bremen using routine and survey data., Methods: The number of individuals with alcohol dependence was estimated using data from the 2018 Epidemiological Survey of Substance Abuse (ESA). Furthermore, linked routine data of two statutory health insurances (SHIs), the German pension insurance (GPI), and the communal hospital group Gesundheit Nord - Bremen Hospital Group (GeNo), from 2016/2017, were analyzed. Based on SHI data, the administrative prevalence of various alcohol-related diagnoses according to the International Classification of Diseases (ICD-10), in various treatment settings, was extrapolated to the total population of Bremen. Based on all routine data sources, treatment and care services for individuals with alcohol dependence were also extrapolated to Bremen's total population. Care services included outpatient addiction care visits and addiction-specific treatments, [i.e., qualified withdrawal treatment (QWT), outpatient pharmacotherapy as relapse prevention, and rehabilitation treatment]., Results: Of the survey-estimated 15,792 individuals with alcohol dependence in Bremen, 72.4% ( n = 11,427) had a diagnosis documented with an ICD-10 code for alcohol dependence (F10.2) or withdrawal state (F10.3-4). One in 10 individuals with alcohol dependence ( n = 1,577) used one or more addiction-specific care services during the observation period. Specifically, 3.7% ( n = 675) received outpatient addiction care, 3.9% ( n = 736) initiated QWT, 0.8% ( n = 133) received pharmacotherapy, and 2.6% ( n = 405) underwent rehabilitation treatment. The share of seeking addiction-specific treatment after diagnosis was highest among younger and male patients., Conclusion: Although more than half of the individuals with alcohol dependence are documented in the health system, utilization rates of addiction-specific treatments are low. These low utilization rates suggest that there are existing barriers to transferring patients with alcohol dependence into addiction-specific care. Strengthening primary medical care provision in dealing with alcohol-related disorders and improving networking within the addiction support system appear to be particularly appropriate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Möckl, Lindemann, Manthey, Schulte, Reimer, Pogarell and Kraus.)

Background: Taxation increases which reduce the affordability of alcohol are expected to reduce mortality inequalities. A recent taxation increase in Lithuania offers the unique possibility to test this hypothesis., Methods: Census-linked mortality data between 2011 and 2019 were used to calculate monthly sex- and education-stratified age-standardized mortality rates for the population aged 40 to 70 years. As primary outcome, we analysed the difference in age-standardized all-cause mortality rates between the population of lowest versus highest educational achievement. The impact of the 2017 taxation increase was evaluated using interrupted time series analyses. To identify whether changes in alcohol use can explain the observed effects on all-cause mortality, the education-based mortality differences were then decomposed into n = 16 cause-of-death groupings., Results: Between 2012 and 2019, education-based all-cause mortality inequalities in Lithuania declined by 18% among men and by 14% among women. Following the alcohol taxation increase, we found a pronounced yet temporary reduction of mortality inequalities among Lithuanian men (- 13%). Subsequent decomposition analyses suggest that the reduction in mortality inequalities between lower and higher educated men was mainly driven by narrowing mortality differences in injuries and infectious diseases., Conclusions: A marked increase in alcohol excise taxation was associated with a decrease in mortality inequalities among Lithuanian men. More pronounced reductions in deaths from injuries and infectious diseases among lower as compared to higher educated groups could be the result of differential changes in alcohol use in these populations., (© 2023. The Author(s).)

Aim: To examine whether in Europe perceptions of 'alcoholism' differ in a discrete manner according to geographical area., Method: Secondary analysis of a data set from a European project carried out in 2013-2014 among 1767 patients treated in alcohol addiction units of nine countries/regions across Europe. The experience of all 11 DSM-4 criteria used for diagnosing 'alcohol dependence' and 'alcohol abuse' were assessed in patient interviews. The analysis was performed through Multiple Correspondence Analysis., Results: The symptoms of 'alcohol dependence' and 'alcohol abuse', posited by DSM-IV, were distributed according to three discrete geographical patterns: a macro-area mainly centered on drinking beer and spirit, a culture traditionally oriented toward wine and a mixed intermediate alcoholic beverage situation., Conclusion: These patterns of perception seem to parallel the diverse drinking cultures of Europe., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: A classic methodology used in evaluating the impact of health policy interventions is interrupted time-series (ITS) analysis, applying a quasi-experimental design that uses both pre- and post-policy data without randomization. In this paper, we took a simulation-based approach to estimating intervention effects under different assumptions., Methods: Each of the simulated mortality rates contained a linear time trend, seasonality, autoregressive, and moving-average terms. The simulations of the policy effects involved three scenarios: 1) immediate-level change only, 2) immediate-level and slope change, and 3) lagged-level and slope change. The estimated effects and biases of these effects were examined via three matched generalized additive mixed models, each of which used two different approaches: 1) effects based on estimated coefficients (estimated approach), and 2) effects based on predictions from models (predicted approach). The robustness of these two approaches was further investigated assuming misspecification of the models., Results: When one simulated dataset was analyzed with the matched model, the two analytical approaches produced similar estimates. However, when the models were misspecified, the number of deaths prevented, estimated using the predicted vs. estimated approaches, were very different, with the predicted approach yielding estimates closer to the real effect. The discrepancy was larger when the policy was applied early in the time-series., Conclusion: Even when the sample size appears to be large enough, one should still be cautious when conducting ITS analyses, since the power also depends on when in the series the intervention occurs. In addition, the intervention lagged effect needs to be fully considered at the study design stage (i.e., when developing the models)., (© 2022. The Author(s).)

People with alcohol-related liver disease (ALD) experience stigma and discrimination. This review summarises the evidence on stigma in healthcare and its implications for people with ALD, drawing from the literature on the stigma associated with mental illness and, specifically, alcohol use disorder (AUD). Public stigma, self-stigma and structural stigma all contribute to failure to seek help or delays in seeking help, inferior healthcare, and negative health outcomes, which increase the overall burden of ALD. Stigma can be experienced, but also anticipated and avoided, with both scenarios negatively impacting on ALD healthcare. Blaming people with ALD for their condition is central to the stigma of ALD. Stigma affects ALD healthcare at all stages, from prevention, early detection and intervention, to allocation of scarce resources in liver transplantation. People with lived experience need to be empowered to lead action against the stigmatisation of patients with ALD. Promulgating a dynamic model of individual and social responsibility for AUD, a continuum model of harmful alcohol use, and establishing training on ALD-related stigma for healthcare professionals are strategies to address stigma. Integrating addiction and ALD services, providing stigma-free prevention, and overcoming the frequent separation of addiction services from general healthcare are necessary. Beyond healthcare, addressing social inequality, the social dimensions of ALD risk and outcomes, and ensuring equal access to services is necessary to improve outcomes for all people with ALD. More research is needed on the stigma of ALD in low- and middle-income countries and in countries with restrictive drinking norms. Interventions to reduce the stigma of ALD and facilitate early help-seeking need to be developed and evaluated., Competing Interests: Conflict of interest GS has received speaker’s honoraria from Lundbeck; AL, JM, JM, MN, CK, SS, PW and PWC report no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Aims: To determine the effect of an alcohol policy change, which increased the minimum legal drinking age (MLDA) from 18 years of age to 20 years of age on all-cause mortality rates in young adults (18-19 years old) in Lithuania., Methods: An interrupted time series analysis was conducted on a dataset from 2001 to 2019 (n = 228 months). The model tested the effects of the MLDA on all-cause mortality rates (deaths per 100,000 individuals) in three age categories (15-17 years old, 18-19 years old, 20-22 years old) in order to control for general mortality trends in young adults, and to isolate the effects of the MLDA from other alcohol control policies. Additional models that included GDP as a covariate and a taxation policy were tested as well., Results: There was a significant effect of the MLDA on all-cause mortality rates in those 18-19 years old, when modelled alone. Additional analyses controlling for the mortality rate of other age groups showed similar findings. Inclusion of confounding factors (policies on alcohol taxation, GDP) eliminated the effects of MLDA., Conclusions: Although there was a notable decline in all-cause mortality rates among young adults in Lithuania, a direct causal impact of MLDA on all-cause mortality rates in young adults was not definitively found., (© The Author(s) 2021. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background and Aims: In India, alcohol per capita consumption (APC) has substantially increased over the past 2 decades. Although consumption does vary across the country, consistent state-level data are lacking. We aimed to identify all state-level alcohol exposure estimates since 2000 to (i) model consistent current drinking (CD) (12 months) prevalence estimates for all 36 states/union territories (UT) in 2019 and (ii) compare state-level CD trends with national-level APC trends., Design: A systematic review for studies on the Indian state-level prevalence of CD, lifetime abstinence (LA), alcohol use disorders (AUD) or the quantity of alcohol consumed among current drinkers (QU) was conducted. Subsequently, statistical modelling was applied., Setting: Data were collected and modelled for all Indian states/UTs., Participants: Studies since 2000 referring to the general adult population (≥15 years) of at least one Indian state/UT were eligible. The total sample size covered was ~29 600 000 (males: females, 1:1.6)., Measurements: Results on LA, AUD and QU were summarized descriptively. For (i) the state-, sex- and age-specific CD prevalence was estimated using random intercept fractional response models. For (ii) random intercept and slope models were performed., Findings: Of 2870 studies identified, 30 were retained for data extraction. LA, AUD and QU data were available for 31, 36 and 12 states/UTs, respectively. CD model estimates ranged from 6.4% (95% CI = 2.1%-18.1%; males) in Lakshadweep and 1.3% (95% CI = 0.7%-2.6%; females) in Delhi to 76.1% (95% CI = 68.1%-82.6%; males) and 63.7% (95% CI = 49.4%-75.7%; females) in Arunachal Pradesh. Over time, CD decreased in most states/UTs in the observed data, contradicting increasing national-level APC trends., Conclusions: Alcohol use (measured as consistent current drinking) in India has large regional variations, with alcohol consumption being most prevalent in the North-East, Chhattisgarh, Telangana, Himachal Pradesh, Punjab and Jharkhand., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: In 2019, Germany was among the countries with the highest alcohol per capita consumption in the world, which contributes significantly to the burden of disease., Aim: In this modelling study, we estimate how many alcohol-attributable diseases and deaths in Germany could have been avoided in 2019 if current alcohol excise taxes were increased by 20%, 50%, and 100%., Methods: The starting point for the modelling was the national beverage-specific alcohol taxes. Three scenarios were modelled under the assumption that the resulting tax increase would be fully transferred to the retail prices. Beverage-specific price elasticities were used. Based on the estimated resulting decline in annual per capita consumption and the disease-specific risk functions, we modelled the avoidable incidence and mortality for alcohol-attributable diseases for 2019. Alcohol-attributable diseases of the cardiovascular and digestive systems, alcohol dependence, epilepsy, and infectious diseases as well as injuries and accidents were considered., Results: Overall, doubling the beverage-specific alcohol taxes could have avoided up to 200,400 alcohol-attributable cases of disease and injury as well as 2800 deaths in Germany in 2019. This corresponds to just under 7% of the modelled new alcohol-attributable cases of disease and death in Germany., Discussion: Alcohol-attributable diseases and injuries are preventable and an increase in the alcohol taxes could substantially reduce the alcohol-attributable burden of disease in Germany., (© 2022. The Author(s).)

Background: The COVID-19 pandemic might impact substance use behaviours around the globe. In this study, we investigate changes in alcohol and tobacco use in the second half of 2020 in countries of the eastern part of the WHO European Region., Methods: Self-reported changes in alcohol and tobacco use among 11 295 adults from 18 countries in the eastern part of the WHO European Region were collected between August 2020 and January 2021. The non-probabilistic sample was weighted for age, gender and education. For each country, proportions of respondents reporting a decrease, no change or increase in substance use over the past 3 months were examined, and multinomial regression models were used to test associations with age, gender and past-year alcohol use., Results: In most countries, about half of the respondents indicating past-year alcohol or tobacco use reported no change in their substance use. Of those alcohol users who reported changes in their alcohol use, a larger proportion reported a decrease than an increase in most countries. The opposite was true for tobacco use. Women, young adults and past-year harmful alcohol users were identified as being more likely to change their substance use behaviour., Conclusion: We found diverging overall trends for alcohol and tobacco use in the second half of 2020. The patterns of change vary according to age, gender and past-year substance use. Individuals at risk to increase their substance use during the COVID-19 pandemic require most policy considerations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: The lack of an agreed international minimum approach to measuring cannabis use hinders the integration of multidisciplinary evidence on the psychosocial, neurocognitive, clinical and public health consequences of cannabis use., Methods: A group of 25 international expert cannabis researchers convened to discuss a multidisciplinary framework for minimum standards to measure cannabis use globally in diverse settings., Results: The expert-based consensus agreed upon a three-layered hierarchical framework. Each layer-universal measures, detailed self-report and biological measures-reflected different research priorities and minimum standards, costs and ease of implementation. Additional work is needed to develop valid and precise assessments., Conclusions: Consistent use of the proposed framework across research, public health, clinical practice and medical settings would facilitate harmonisation of international evidence on cannabis consumption, related harms and approaches to their mitigation., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Issues: Numerous studies have examined the impact of the COVID-19 pandemic on alcohol use changes in Europe, with concerns raised regarding increased use and related harms., Approach: We synthesised observational studies published between 1 January 2020 and 31 September 2021 on self-reported changes in alcohol use associated with COVID-19. Electronic databases were searched for studies evaluating individual data from European general and clinical populations. We identified 646 reports, of which 56 general population studies were suitable for random-effects meta-analyses of proportional differences in alcohol use changes. Variations by time, sub-region and study quality were assessed in subsequent meta-regressions. Additional 16 reports identified were summarised narratively., Key Findings: Compiling reports measuring changes in overall alcohol use, slightly more individuals indicated a decrease than an increase in their alcohol use during the pandemic [3.8%, 95% confidence interval (CI) 0.00-7.6%]. Decreases were also reported more often than increases in drinking frequency (8.0%, 95% CI 2.7-13.2%), quantity consumed (12.2%, 95% CI 8.3-16.2%) and heavy episodic drinking (17.7%, 95% CI 13.6-21.8%). Among people with pre-existing high drinking levels/alcohol use disorder, high-level drinking patterns appear to have solidified or intensified., Implications: Pandemic-related changes in alcohol use may be associated with pre-pandemic drinking levels. Increases among high-risk alcohol users are concerning, suggesting a need for ongoing monitoring and support from relevant health-care services., Conclusion: Our findings suggest that more people reduced their alcohol use in Europe than increased it since the onset of the pandemic. However high-quality studies examining specific change mechanisms at the population level are lacking., (© 2022 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Background and Aims: The relationship between alcohol consumption and cirrhosis is well established. Policies that can influence population-level use of alcohol should, in turn, impact cirrhosis. We examined the effect of population-level alcohol control policies on cirrhosis mortality rates in Lithuania - a high-income European Union country with high levels of alcohol consumption., Methods: Age-standardized, monthly liver mortality data (deaths per 100,000 adults, aged 15+) from Lithuania were analysed from 2001 to 2018 (n = 216 months) while controlling for economic confounders (gross domestic product and inflation). An interrupted time-series analysis was conducted to estimate the effect of three alcohol control policies implemented in 2008, 2017 and 2018 and the number of cirrhosis deaths averted., Results: There was a significant effect of the 2008 (P < .0001) and 2017 (P = .0003) alcohol control policies but a null effect of the 2018 policy (P = .40). Following the 2008 policy, the cirrhosis mortality rate dropped from 4.93 to 3.41 (95% CI: 3.02-3.80) deaths per 100,000 adults, which equated to 493 deaths averted. Further, we found that following the 2017 policy, the mortality rate dropped from 2.85 to 2.01 (95% CI: 1.50-2.52) deaths per 100,000 adults, corresponding to 245 deaths averted., Conclusions: Our findings support the hypothesis that alcohol control policies can have a significant, immediate effect on cirrhosis mortality. These policy measures are cost-effective and aid in reducing the burden of liver disease., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: During the COVID-19 pandemic, an increase of heavy alcohol use has been reported in several high-income countries. We examined changes in alcohol use during the pandemic among primary health care (PHC) patients in two middle income countries, Colombia and Mexico., Methods: Data were collected during routine consultations in 34 PHC centres as part of a large-scale implementation study. Providers measured patients' alcohol consumption with the three item 'Alcohol Use Disorders Identification Test' (AUDIT-C). Generalized linear mixed models were performed to examine changes in two dependent variables over time (pre-pandemic and during pandemic): 1) the AUDIT-C score and 2) the proportion of heavy drinking patients (8+ on AUDIT-C)., Results: Over a period of more than 600 days, data from N = 17 273 patients were collected. During the pandemic, the number of patients with their alcohol consumption measured decreased in Colombia and Mexico. Each month into the pandemic was associated with a 1.5% and 1.9% reduction in the mean AUDIT-C score in Colombia and Mexico, respectively. The proportion of heavy drinking patients declined during the pandemic in Colombia (pre-pandemic: 5.4%, 95% confidence interval (CI) = 4.8% to 6.0%; during the pandemic: 0.8%, 95% CI = 0.6% to 1.1%) but did not change in Mexico., Conclusions: Average consumption levels declined and the prevalence of heavy drinking patterns did not increase. In addition to reduced opportunities for social drinking during the pandemic, changes in the population seeking PHC and restrictions in alcohol availability and affordability are likely drivers for lower levels of alcohol use by patients in this study., Competing Interests: Competing interests: HLP has received training grants in the last 3 years from Lundbeck, and nonfinancial relationships that could be viewed as presenting a potential conflict of interest. The authors completed the ICMJE Unified Competing Interest Form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Spain is one of the countries of the European Union in which alcohol consumption has decreased in the past decades. The aim of this paper is to distinguish different phases of the level of alcohol consumption in Spain since 1990. Adult alcohol consumption per capita data between 1990 and 2019 were analysed for temporal trends using the Joinpoint regression model. An additional analysis using interrupted time-series between 1962 and 2016 was performed using data from Global Information System on Alcohol and Health. Data from the survey on alcohol and other drugs in Spain were collected and a narrative review was conducted to identify possible reasons for the trends found. Five point changes were identified on the timeline between 1990 and 2019, including: a decrease of 3.2% per year from 1990 to 1995, an increase of 1.1% per year from 1995 to 2000, a period of stability from 2000 to 2006, a decrease of 4.5% per year from 2006 to 2011, and a period of stability from 2011 onwards. These changes can largely be explained by the different public health measures carried out by the Spanish government, as well as the change in the pattern of consumption in society, which shifted its alcoholic beverage preference from wine to beer, and increased its binge-drinking behaviour. Further studies such as interrupted time-series analyses should test if indeed the hypothesized measures on public health have been effective; this could inform future policies in Spain and in other countries.

Alcohol measurement in health care settings is an effective intervention for reducing alcohol-related harm. However, in many countries, costs related to alcohol measurement have not yet been transparently assessed, which may hinder its adoption and implementation. Costs of an alcohol measurement programme in three upper-middle-income Latin American countries were assessed via questionnaires and compared, as part of the quasi-experimental SCALA study. Additional to the intervention costs, the costs of three implementation strategies: standard training and clinical package, intensive training and clinical package, and community support, were assessed and subsequently translated into costs per additional alcohol measurement session. Results demonstrated that costs for one alcohol measurement session ranged between Int$ 0.67 and Int$ 1.23 in Colombia, Int$ 1.19 and Int$ 2.57 in Mexico, and Int$ 1.11 and Int$ 2.14 in Peru. Costs were mainly driven by the salaries of the health professionals. Implementation strategies costs per additional alcohol measurement session ranged between Int$ 1.24 and Int$ 6.17. In all three countries, standard training and a clinical package may be a promising implementation strategy with a relatively low cost per additional alcohol measurement session.

Aim: Recording the frequency of screenings for problematic alcohol consumption by professionals involved in the health care of respective patients. The German S3-guideline "screening, diagnosis and treatment of alcohol-related disorders" recommends the use of questionnaire-based screenings for all patients in all settings., Methods: Cross-sectional survey on screening frequency among general practitioners, gynecologists, psychiatrists, child- and adolescent therapists, psychotherapists, social workers and midwives. Logistic regression was used to explore how healthcare professionals' attributes were associated with the implementation of screenings., Results: With response rates of about 20%, health care professionals reported using screening instruments for an average of 6.9% of all patients during the previous four weeks. Most of the time, custom-made questions were used instead of the recommended instruments (AUDIT, AUDIT-C). Higher screening rates were reported for patients with newly diagnosed hypertension (21.2%), alcohol-related disorders (43.3%) and mental disorders (39.3%). Knowledge of the guideline was associated with implementation of screenings (OR=4.67; 95% KI 1.94-11.25, p<0.001)., Conclusions: Comprehensive screening for problematic alcohol use with questionnaire-based instruments in accordance with guidelines is far from being routinely implemented in the studied health care settings. Measures to increase the knowledge of the guidelines are necessary in order to increase the frequency of alcohol screening in health care., Competing Interests: U.Frischknecht bezog ein Honorar vom Thieme Verlag für die Autorenschaft an einer Publikation zu einem verwandten Thema. J.Manthey nahm als Referent am Wissenschaftlichen Gespräch der Deutschen Gesellschaft für Suchtforschung und Suchttherapie e.V. (DGSucht) teil, wofür er ein Honorar erhielt sowie Reise-, Übernachtungs- und Kongresskosten erstattet wurden. J.Reimer erhielt Unterstützung vom Bundesministerium für Gesundheit für die Abfassung des vorliegenden Manuskripts bzw. thematisch verwandter Arbeiten. F.Kiefer war als Referent für die Amomed Pharma GmbH tätig. J.Rehm erhielt Gelder für Studien zu Epidemiologie und Alkoholabhängigkeit von der Lundbeck GmbH und der D&A Pharma GmbH. L.Kraus wurde in einem Forschungsprojekt zur Epidemiologie von Alkoholabhängigkeit von Lundbeck GmbH gefördert. S.Hoffmann, A.Steinhauser, C.Lindemann, A.Buchholz, C.Lindemann, U.Verthein, und B.Schulte geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: The year 2020 was marked by the COVID-19 pandemic. Policy responses to COVID-19 affected social and economic life and the availability of alcohol. Previous research has shown an overall small decrease in alcohol use in Denmark in the first months of the pandemic. The present paper focused on identifying which subgroups of individuals had decreased or increased their consumption., Materials and Methods: Data were collected between May and July 2020 (n = 2,566 respondents, convenience sample). Weights were applied to reflect the actual Danish general population. Variables included the pre-pandemic alcohol consumption, change in alcohol consumption in the past month, socio-demographics, and reported economic consequences. Responses to a single item assessing changes in alcohol consumption in the past month were classified as no change, increase, or decrease in consumption. Regression models investigated how changes in consumption were linked to pre-pandemic drinking levels, socio-demographics (gender, age groups, education), and reported economic consequences., Results: While 39% of participants reported decreased consumption levels and 34% had stable levels, 27% increased consumption. Characteristics associated with changes in consumption were associated with both increases and decreases in consumption: younger people, those with higher consumption levels before the pandemic, and those with lower education more often both reported increases as well as decreases in consumption., Discussion/conclusions: We confirmed that more people decreased rather than increased their alcohol consumption in the first few months of the pandemic in Denmark. Characteristics associated with changes in consumption such as younger age, higher consumption levels, and lower education demonstrated a polarization of drinking since these were associated with both increases and decreases in consumption. Public health authorities should monitor alcohol use and other health behaviours for increased risks during the pandemic., (The Author(s). Published by S. Karger AG, Basel.)

Introduction: Stigma towards alcohol-related conditions is more pronounced than stigma against any other mental illness and has remained high throughout past decades. Although alcohol consumption is a known and persistent contributor to the burden of disease and interpersonal threat and may thus shape public attitudes towards consumption, no study to date has provided an overview of the prevalence of alcohol stigma and its association with (a) alcohol consumption and (b) harm attributable to alcohol across Europe. As a social reaction to thresholds of accepted use of alcohol, stigma could impact consumption, resulting in a reduced quantity or at least less harmful drinking patterns. This contribution provides an initial overview by addressing the following research questions. (i) What are the country-level prevalence rates of alcohol stigma compared across European countries? (ii) Is alcohol stigma associated with (a) alcohol consumption and (b) alcohol-attributable harm? (iii) Is there an association between alcohol stigma and alcohol consumption by type of beverage?, Methods: We combined data on country-level desire for social distance towards "heavy drinkers" (European Values Survey, operationalization of "alcohol stigma") with indicators of alcohol consumption, including adult per capita consumption (APC), heavy episodic drinking, consumption by type of beverage (wine, beer, spirits), and harm attributable to alcohol, namely age-standardized disability-adjusted life years lost to alcohol consumption (AADALYs) for 28 countries. Linear regression models were applied., Results: (i) Social distance varied noticeably across countries (M = 62.9%, SD = 16.3%) in a range of 28.3% and 87.3%. (ii) APC was significantly positive related to social distance (β = 0.55, p = 0.004). (iii) Wine consumption was significantly negative related to social distance; the opposite was true for spirits consumption. No association was found for beer consumption. The best model fit was achieved with APC (β = 0.48, p = 0.002) and wine per capita consumption (β = -0.55, p < 0.001) explaining 57.0% (adjusted R2) of the variance in social distance., Conclusion: Our study shows a strong relationship between country-level alcohol stigma and alcohol consumption. If stigma was to deter people from harmful alcohol consumption, it would be expected that higher levels of alcohol stigma are associated with lower levels of overall alcohol consumption or consumption of spirits in particular. Instead, stigma seems to be a reaction to harmful drinking patterns without changing these patterns for the better., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Objectives: As unrecorded alcohol use contributes to a substantial burden of disease, this study characterises this phenomenon in newly independent states (NIS) of the former Soviet Union with regard to the sources of unrecorded alcohol, and the proportion of unrecorded of total alcohol consumption. We also investigate associated sociodemographic characteristics and drinking patterns., Design: Cross-sectional data on overall and unrecorded alcohol use in the past 7 days from WHO STEPwise Approach to NCD Risk Factor Surveillance (STEPS) surveys. Descriptive statistics were calculated at the country level, hierarchical logistic and linear regression models were used to investigate sociodemographic characteristics and drinking patterns associated with using unrecorded alcohol., Setting: Nine NIS (Armenia, Azerbaijan, Belarus, Georgia, Kyrgyzstan, Republic of Moldova, Tajikistan, Turkmenistan and Uzbekistan) in the years 2013-2017., Participants: Nationally representative samples including a total of 36 259 participants., Results: A total of 6251 participants (19.7%; 95% CI 7.9% to 31.5%) reported alcohol consumption in the past 7 days, 2185 of which (35.1%; 95% CI 8.2% to 62.0%) reported unrecorded alcohol consumption with pronounced differences between countries. The population-weighted average proportion of unrecorded consumption in nine NIS was 8.7% (95% CI 5.9% to 12.4%). The most common type of unrecorded alcohol was home-made spirits, followed by home-made beer and wine. Older (45-69 vs 25-44 years) and unemployed (vs employed) participants had higher odds of using unrecorded alcohol. More nuanced sociodemographic differences were observed for specific types of unrecorded alcohol., Conclusions: This contribution is the first to highlight both, prevalence and composition of unrecorded alcohol consumption in nine NIS. The observed proportions and sources of unrecorded alcohol are discussed in light of local challenges in policy implementation, especially in regard to the newly formed Eurasian Economic Union (EAEU), as some but not all NIS are in the EAEU., Competing Interests: Competing interests: IR reports grants from WHO is funded by all Governments of Member States. WHO NCD Office is funded by voluntary donation from the Government of the Russian Federation during the conduct of the study. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Alcohol use is a major risk factor for mortality. Previous studies suggest that the alcohol-attributable mortality burden is higher in lower socioeconomic strata. This project will test the hypothesis that the 2017 increase of alcohol excise taxes linked to lower all-cause mortality rates in previous analyses will reduce socioeconomic mortality inequalities., Methods and Analysis: Data on all causes of deaths will be obtained from Statistics Lithuania. Record linkage will be implemented using personal identifiers combining data from (1) the 2011 whole-population census, (2) death records between 1 March 2011 (census date) and 31 December 2019, and (3) emigration records, for individuals aged 40-70 years. The analyses will be performed separately for all-cause and for alcohol-attributable deaths. Monthly age-standardised mortality rates will be calculated by sex, education and three measures of socioeconomic status (SES). Inequalities in mortality will be assessed using absolute and relative indicators between low and high SES groups. We will perform interrupted time series analyses, and test the impact of the 2017 rise in alcohol excise taxation using generalised additive mixed models. In these models, we will control for secular trends for economic development., Ethics and Dissemination: This work is part of project grant 1R01AA028224-01 by the National Institute on Alcohol Abuse and Alcoholism. It has been granted research ethics approval 050/2020 by Centre for Addiction and Mental Health Research Ethics Board on 17 April 2020, renewed on 30 March 2021. The time series of mortality inequalities as well as the statistical code will be made publicly available, allowing other researchers to adapt the proposed method to other jurisdictions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To investigate changes in alcohol consumption during the first months of the COVID-19 pandemic in Europe as well as its associations with income and experiences of distress related to the pandemic., Design: Cross-sectional on-line survey conducted between 24 April and 22 July 2020., Setting: Twenty-one European countries., Participants: A total of 31 964 adults reporting past-year drinking., Measurements: Changes in alcohol consumption were measured by asking respondents about changes over the previous month in their drinking frequency, the quantity they consumed and incidence of heavy episodic drinking events. Individual indicators were combined into an aggregated consumption-change score and scaled to a possible range of -1 to +1. Using this score as the outcome, multi-level linear regressions tested changes in overall drinking, taking into account sampling weights and baseline alcohol consumption [Alcohol Use Disorder Identification Test (AUDIT-C)] and country of residence serving as random intercept. Similar models were conducted for each single consumption-change indicator., Findings: The aggregated consumption-change score indicated an average decrease in alcohol consumption of -0.14 [95% confidence interval (CI) = -0.18, -0.10]. Statistically significant decreases in consumption were found in all countries, except Ireland (-0.08, 95% CI = -0.17, 0.01) and the United Kingdom (+0.10, 95% CI = 0.03, 0.17). Decreases in drinking were mainly driven by a reduced frequency of heavy episodic drinking events (-0.17, 95% CI = -0.20, -0.14). Declines in consumption were less marked among those with low- or average incomes and those experiencing distress., Conclusions: On average, alcohol consumption appears to have declined during the first months of the COVID-19 pandemic in Europe. Both reduced availability of alcohol and increased distress may have affected consumption, although the former seems to have had a greater impact in terms of immediate effects., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Issues: Alcohol use has been shown to impact on various forms of liver disease, not restricted to alcoholic liver disease., Approach: We developed a conceptual framework based on a narrative review of the literature to identify causal associations between alcohol use and various forms of liver disease including the complex interactions of alcohol with other major risk factors. Based on this framework, we estimate the identified relations for 2017 for the USA., Key Findings: The following pathways were identified and modelled for the USA for the year 2017. Alcohol use caused 35 200 (95% uncertainty interval 32 800-37 800) incident cases of alcoholic liver cirrhosis. There were 1700 (uncertainty interval 1100-2500) acute hepatitis B and C virus (HBV and HCV) infections attributable to heavy-drinking occasions, and 14 000 (uncertainty interval 5900-19 500) chronic HBV and 1700 (uncertainty interval 700-2400) chronic HCV infections due to heavy alcohol use interfering with spontaneous clearance. Alcohol use and its interactions with other risk factors (HBV, HCV, obesity) led to 54 500 (uncertainty interval 50 900-58 400) new cases of liver cirrhosis. In addition, alcohol use caused 6600 (uncertainty interval 4200-9300) liver cancer deaths and 40 700 (uncertainty interval 36 600-44 600) liver cirrhosis deaths., Implications: Alcohol use causes a substantial number of incident cases and deaths from chronic liver disease, often in interaction with other risk factors., Conclusion: This additional disease burden is not reflected in the current alcoholic liver disease categories. Clinical work and prevention policies need to take this into consideration., (© 2021 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Competing Interests: Declarations of Interest Author CH is employed by GW Pharmaceuticals. Her substantive contribution to this publication occurred before employment at GW pharmaceuticals. All authors have declared no conflict of interest related to this topic.

This paper explores trends in beverage preference in adolescents, identifies related regional differences, and examines cluster differences in key drinking measures. Data were obtained from the European School Survey Project on Alcohol and Other Drugs (ESPAD), covering 24 European countries between 1999 and 2019. Trends in the distribution of alcoholic beverages on the participants' most recent drinking occasion were analysed by sex and country using fractional multinomial logit regression. Clusters of countries based on trends and predicted beverage proportions were compared regarding the prevalence of drinkers, mean alcohol volume and prevalence of heavy drinking. Four distinct clusters each among girls and boys emerged. Among girls, there was not one type of beverage that was preferred across clusters, but the proportion of cider/alcopops strongly increased over time in most clusters. Among boys, the proportion of beer decreased, but was dominant across time in all clusters. Only northern European countries formed a geographically defined region with the highest prevalence of heavy drinking and average alcohol volume in both genders. Adolescent beverage preferences are associated with mean alcohol volume and heavy drinking at a country-level. Future approaches to drinking cultures need to take subpopulations such as adolescents into account.

Evidence suggests that changes in alcohol consumption during the first months of the COVID-19 pandemic were unevenly distributed over consumer groups. We investigated possible inter-country differences in how changes in alcohol consumption are contingent on initial consumption (before or at the start of the pandemic), and how changes in consumption translate into possible changes in the prevalence of heavy drinking. We used data from the European Survey on Alcohol use and COVID-19 (ESAC) conducted in Czechia, Denmark, Finland, Germany, Norway, Poland, Spain, and the UK (N = 31921). Past-year alcohol consumption and changes in consumption were measured by AUDIT-C. Drinking habits were compared according to percentiles of pre-pandemic consumption levels, below versus above the 90th percentile. Across countries, drinkers in the highest 10% for pre-pandemic consumption increased their drinking during the pandemic, whereas absolute changes among those initially drinking below this level were modest. The percentage of people reporting >28 alcohol units/week increased significantly in seven of eight countries. During the first months of the COVID-19 pandemic, alcohol consumption in the upper decile of the drinkers increased as did the prevalence of heavy drinkers, in contrast with a declining consumption in other groups in the sample.

Background and Aims: Alcohol use has been identified as a major risk factor for burden of mortality and disease, particularly for countries in eastern Europe. During the past two decades, several countries in this region have implemented effective alcohol policy measures to combat this burden. The aim of the current study was to measure the association between Lithuania's alcohol control policies and adult all-cause mortality., Design: Interrupted time-series methodology by means of general additive models., Setting: Lithuania., Participants: Adult population of Lithuania, aged 20 years and older., Measurements: Alcohol control policies were ascertained via a document review of relevant legislation materials. Policy effects were evaluated as follows: (1) slope changes in periods of legislative (non-)activity with regard to alcohol control policy (analysis 1); (2) level changes of three interventions following recommendations of the World Health Organization (analysis 2); and (3) level changes of seven interventions judged a priori by an international panel of experts (analysis 3). Mortality was measured by sex-stratified and total monthly age-standardized rates of all-cause mortality for the adult population., Findings: During the period 2001-18, effective alcohol control policy measures were implemented on several occasions, and in those years the all-cause mortality rate declined by approximately 3.2% more than in years without such policies. In particular, the implementation of increased taxation in 2017 was associated with reduced mortality over and above the general trend for men and in total for all analyses, which amounted to 1452 deaths avoided (95% confidence interval = -166 to -2739) in the year following the implementation of the policy., Conclusions: Alcohol control policies in Lithuania appear to have reduced the overall adult all-cause mortality over and above secular trends., (© 2021 Society for the Study of Addiction.)

Introduction: This contribution gives an overview on estimating the economic impact of substance use (SU) and substance use disorders (SUDs) from a societal perspective., Areas Covered: In this Expert Review, we first discuss the scope of the economic costs of SU to society and the methods used to estimate them. In general, cost studies should not be limited to SUDs, but should also include costs related to the consequences of any type of SU to achieve a comprehensive picture of the societal burden. Further, estimating potentially avoidable costs will increase the value of cost studies. Importantly, methodologically sound cost studies shed light on the magnitude of societal problems related to SU and can be used as a reference point to evaluate regulatory policies and other preventive measures. The area of estimating potential economic benefits of SU is understudied and lacks a theoretical and methodological framework., Expert Opinion: Overall, economic studies on the impact of SU and SUDs can strongly contribute to better-informed decision-making in the creation of regulatory and control policies. The least developed area of research refers to a consensus methodology that could be used in studies which compare economic costs to potential economic benefits.

Background and Importance: SBIRT programs (Screening Brief Intervention and Referral to Treatment) for at-risk drinkers in emergency departments (ED) have shown to be effective, particularly at short term. In this article, we report mid and long-term follow-up results of a specialized SBIRT program. A short-term follow-up after 1.5 months showed encouraging results, with more than a 20% greater reduction of at-risk drinking in the intervention group and more than double of successful referrals to specialized treatment., Objective: We aimed to evaluate the mid and long-term efficacy of an SBIRT program conducted by psychiatrist specialists in addictive disorders and motivational interviewing in the ED of a tertiary hospital., Design, Settings and Participants: We conducted a secondary analysis of a previously published randomized controlled trial of an SBIRT program conducted by alcohol specialists for at-risk drinkers presenting to the ED, measured with the AUDIT-C scale., Intervention or Exposure: Patients were randomized into two groups, with the control group receiving two leaflets: one regarding alcohol use and the other giving information about the study protocol. The intervention group received the same leaflets as well as a brief motivational intervention on alcohol use and, where appropriate, a referral to specialized treatment., Outcomes Measure and Analysis: Long-term assessment primary outcome was the proportion of at-risk alcohol use measured by AUDIT-C scale. The main effectiveness analysis at 18 weeks and 12 months' follow-up was conducted with multilevel logistic regression analyses. Missing values were imputed with the last observation carried forward., Main Results: Of 200 patients included in the study, 133 (66.5%) and 131 (65.5%) completed 18 weeks and 1-year follow-up respectively. Although the proportion of risky drinkers was substantially lower in the intervention group (38.5 vs. 57.4% at 4.5 months and 58.5 vs 68.2% at 1 year), these results did not reach statistical significance (OR = 2.15; CI, 0.87-5.33)., Conclusions: In this secondary analysis for mid- and long-term effects of a specialized SBIRT program, there was no significant difference in the reduction of risky drinkers at 18 weeks and 1 year. The small size of the studied sample and the low retention rate precluded any significant conclusion, although point estimates suggest a positive effect. Overall, SBIRT programs are an effective tool to reduce alcohol use at short time and to refer patients to specialized treatment; however, its effects seem to decay over time., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cannabis is one of the most widely used substances worldwide. Heavy use is associated with an increased risk of cannabis use disorders, psychotic disorders, acute cognitive impairment, traffic injuries, respiratory problems, worse pregnancy outcomes, and there are indications for genotoxic and epigenotoxic adverse effects. International regulation of medical and non-medical cannabis use is changing rapidly and substantially, highlighting the importance of robust public health monitoring. This study aimed to describe the trends of key public health indicators in European Union (27 member states + UK, Norway and Turkey) for the period 2010 to 2019, their public health implications, and to identify the steps required to improve current practice in monitoring of cannabis use and harm in Europe., Methods: Data on four key cannabis indicators (prevalence of use, prevalence of cannabis use disorder [CUD], treatment rates, and potency of cannabis products) in Europe were extracted from the United Nations Office on Drugs and Crime, European Monitoring Centre for Drugs and Drug Addiction and the Global Burden of Disease study. For prevalence of use and CUD, the first and last available estimate in each country were compared. For treatment rates and cannabis potency, linear regression models were conducted., Findings: Between 2010 and 2019, past-month prevalence of cannabis use increased by 27% in European adults (from 3·1 to 3·9%), with most pronounced relative increases observed among 35-64 year-olds. In 13 out of 26 countries, over 20% of all past-month users reported high-risk use patterns. The rate of treatment entry for cannabis problems per 100,000 adults increased from 27·0 (95% CI: 17·2 to 36·8) to 35·1 (95% CI: 23·6 to 46·7) and has mostly plateaued since 2015. Modest increases in potency were found in herbal cannabis (from 6·9% to 10·6% THC) while median THC values tripled in cannabis resin (from 7·6% to 24·1% THC)., Interpretation: In the past decade, cannabis use, treatment rates and potency levels have increased in Europe highlighting major concerns about the public health impact of cannabis use. Continued monitoring and efforts to improve data quality and reporting, including indicators of high-risk use and cannabis-attributable harm, will be necessary to evaluate the health impact of international changes in cannabis regulation., Funding: This study received no specific funding., Competing Interests: H.L.P. works under the CERCA Programme/Generalitat de Catalunya and receives funding from the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III through a “Juan Rodes” contract (JR19/00025). The remaining authors declare no conflict of interest., (© 2021 The Author(s).)

Objectives: This contribution provides insights into the methodology of a pan-European population-based online survey, performed without external funding during the COVID-19 pandemic. We present the impact of different dissemination strategies to collect data from a non-probabilistic convenience sample and outline post-stratification weighting schemes, to provide guidance for future multi-country survey studies., Methods: Description and comparison of dissemination strategies for five exemplary countries (Czechia, Germany, Lithuania, Norway, Spain) participating in the Alcohol Use and COVID-19 Survey. Comparison of the sample distribution with the country's actual population distribution according to sociodemographics, and development of weighting schemes., Results: The dissemination of online surveys through national newspapers, paid social media adverts and dissemination with the support of national health ministries turned out to be the most effective strategies. Monitoring the responses and adapting dissemination strategies to reach under-represented groups, and the application of sample weights were helpful to achieve an analytic sample matching the respective general population profiles., Conclusion: Reaching a large pan-European convenience sample, including most European countries, in a short time was feasible, with the support of a broad scientific network., (© 2021 The Authors. International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.)

Purpose: We aimed to test the effects of providing municipal support and training to primary health care providers compared to both training alone and to care as usual on the proportion of adult patients having their alcohol consumption measured., Methods: We undertook a quasi-experimental study reporting on a 5-month implementation period in 58 primary health care centres from municipal areas within Bogotá (Colombia), Mexico City (Mexico), and Lima (Peru). Within the municipal areas, units were randomized to four arms: (1) care as usual (control); (2) training alone; (3) training and municipal support, designed specifically for the study, using a less intensive clinical and training package; and (4) training and municipal support, designed specifically for the study, using a more intense clinical and training package. The primary outcome was the cumulative proportion of consulting adult patients out of the population registered within the centre whose alcohol consumption was measured (coverage)., Results: The combination of municipal support and training did not result in higher coverage than training alone (incidence rate ratio (IRR) = 1.0, 95% CI = 0.6 to 0.8). Training alone resulted in higher coverage than no training (IRR = 9.8, 95% CI = 4.1 to 24.7). Coverage did not differ by intensity of the clinical and training package (coefficient = 0.8, 95% CI 0.4 to 1.5)., Conclusions: Training of providers is key to increasing coverage of alcohol measurement amongst primary health care patients. Although municipal support provided no added value, it is too early to conclude this finding, since full implementation was shortened due to COVID-19 restrictions., Trial Registration: Clinical Trials.gov ID: NCT03524599; Registered 15 May 2018; https://clinicaltrials.gov/ct2/show/NCT03524599., (© 2021. The Author(s).)

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%., Competing Interests: Conflict of interest The authors declare no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021. Published by Elsevier B.V.)

Background: Brief interventions (BI) for risky drinkers in primary healthcare have been demonstrated to be cost-effective but they are still poorly implemented. Digital BI seems to be a complementary strategy to overcome some barriers to implementation but there is a scarcity of studies in clinical environments. We present the results of a randomized controlled non-inferiority trial which tests the non-inferiority of facilitated access to a digital intervention (experimental condition) for risky drinkers against a face-to-face BI (control condition) provided by primary healthcare professionals., Method: In a non-inferiority randomized controlled trial, unselected primary healthcare patients (≥ 18 years old) were given a brief introduction and asked to log on to the study website to fill in the 3-item version of the Alcohol Use Disorders Identification Test. Positively screened patients (4+ for women and 5+ for men) received further online assessment (AUDIT, socio-demographic characteristics and EQ-5D-5L) and were automatically randomized to either face-to-face or digital BI (1:1). The primary outcome was the proportion of patients classified as risky drinkers by the digitally administered AUDIT at month 3. A multiple imputation approach for the missing data was performed., Results: Of the 4499 patients approached by 115 healthcare professionals, 1521 completed the AUDIT-C. Of the 368 positively screened patients, 320 agreed to participate and were randomized to either intervention. At month 3, there were more risky drinkers in the experimental group (59.8%) than in the control group (52%), which was similar to the distribution at baseline and less than the pre-specified margin of 10%. The difference was not significant when accounting for possible confounders., Conclusion: Digital BI was not inferior to face-to-face BI, in line with previous findings and the a priori hypothesis. However, the low power of the final sample, due to the low recruitment and loss to follow-up, limits the interpretation of the findings. New approaches in this field are required to ensure the effective implementation of digital interventions in actual practice., Competing Interests: AG has received honoraria, research grants and travel grants from Lundbeck and D&A Pharma, which had no bearing on the research of this study. HL-P has received travel grants from Lundbeck, and Otsuka, and honoraria from Lundbeck which had no bearing on the research of this study. The other authors do not provide any competing interests., (© 2021 Published by Elsevier B.V.)

Background: Cannabis is the third most consumed drug worldwide. Thus, healthcare providers should be able to identify users who are in need for an intervention. This study aims to explore the relationship of acute, chronic, and early exposure (AE, CE, and EE) to cannabis with cognitive and behavioral harms (CBH), as a first step toward defining risky cannabis use criteria. Methods: Adults living in Spain who used cannabis at least once during the last year answered an online survey about cannabis use and health-related harms. Cannabis use was assessed in five dimensions: quantity on use days during the last 30 days (AE), frequency of use in the last month (AE), years of regular use (YRCU) (CE), age of first use (AOf) (EE), and age of onset of regular use (AOr) (EE). CBH indicators included validated instruments and custom-made items. Pearson correlations were calculated for continuous variables, and Student's t -tests for independent samples were calculated for categorical variables. Effect sizes were calculated for each of the five dimensions of use (Cohen's d or r Pearson correlation) and harm outcome. Classification and Regression Trees (CART) analyses were performed for those dependent variables (harms) significantly associated with at least two dimensions of cannabis use patterns. Lastly, logistic binary analyses were conducted for each harm outcome. Results: The mean age of participants was 26.2 years old [standard deviation (SD) 8.5]. Out of 2,124 respondents, 1,606 (75.6%) reported at least one harm outcome (mean 1.8 and SD 1.5). In our sample, using cannabis on 3 out of 4 days was associated with an 8-fold probability of scoring 4+ on the Severity Dependence Scale (OR 8.33, 95% CI 4.91-14.16, p <0.001), which is indicative of a cannabis use disorder. Also, a start of regular cannabis use before the age of 25 combined with using cannabis at least once per month was associated with a higher probability of risky alcohol use (OR 1.33, 95% CI 1.12-1.57, p = 0.001). Besides, a start of regular cannabis use before the age of 18 combined with a period of regular use of at least 7.5 years was associated with a higher probability of reporting a motor vehicle accident (OR 1.81, 95% CI 1.41-2.32, p < 0.0001). Results were ambiguous regarding the role that age of first use and milligrams of THC per day of use might play regarding cannabis-related harms. Conclusions: The relationship among AE, CE, and EE with CBH indicators is a complex phenomenon that deserves further studies. The pattern of cannabis use should be carefully and widely evaluated-(not just including frequency but also other dimensions of pattern of use)-in research (preferably in longitudinal studies) to assess cannabis-related harms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 López-Pelayo, Campeny, Oliveras, Rehm, Manthey, Gual and Balcells-Olivero.)

Introduction: Implementation of evidence-based care for heavy drinking and depression remains low in global health systems. We tested the impact of providing community support, training, and clinical packages of varied intensity on depression screening and management for heavy drinking patients in Latin American primary healthcare., Materials and Methods: Quasi-experimental study involving 58 primary healthcare units in Colombia, Mexico and Peru randomized to receive: (1) usual care (control); (2) training using a brief clinical package; (3) community support plus training using a brief clinical package; (4) community support plus training using a standard clinical package. Outcomes were proportion of: (1) heavy drinking patients screened for depression; (2) screen-positive patients receiving appropriate support; (3) all consulting patients screened for depression, irrespective of drinking status., Results: 550/615 identified heavy drinkers were screened for depression (89.4%). 147/230 patients screening positive for depression received appropriate support (64%). Amongst identified heavy drinkers, adjusting for country, sex, age and provider profession, provision of community support and training had no impact on depression activity rates. Intensity of clinical package also did not affect delivery rates, with comparable performance for brief and standard versions. However, amongst all consulting patients, training providers resulted in significantly higher rates of alcohol measurement and in turn higher depression screening rates; 2.7 times higher compared to those not trained., Conclusions: Training using a brief clinical package increased depression screening rates in Latin American primary healthcare. It is not possible to determine the effectiveness of community support on depression activity rates due to the impact of COVID-19., Competing Interests: The authors have declared that no competing interests exist.

Background: Screening, brief intervention and referral to treatment (SBIRT) is a programme to reduce alcohol consumption for drinkers with high alcohol consumption levels. Only 2.9% of patients in primary health care (PHC) are screened for their alcohol use in Germany, despite high levels of alcohol consumption and attributable harm. We developed an open-access simulation model to estimate the impact of higher SBIRT delivery rates in German PHC settings on population-level alcohol consumption., Methods and Findings: A hypothetical population of drinkers and non-drinkers was simulated by sex, age, and educational status for the year 2009 based on survey and sales data. Risky drinking persons receiving BI or RT were sampled from this population based on screening coverage and other parameters. Running the simulation model for a ten-year period, drinking levels and heavy episodic drinking (HED) status were changed based on effect sizes from meta-analyses. In the baseline scenario of 2.9% screening coverage, 2.4% of the adult German population received a subsequent intervention between 2009 and 2018. If every second PHC patient would have been screened for alcohol use, 21% of adult residents in Germany would have received BI or RT by the end of the ten-year simulation period. In this scenario, population-level alcohol consumption would be 11% lower than it was in 2018, without any impact on HED prevalence. Screening coverage rates below 10% were not found to have a measurable effect on drinking levels., Conclusions: Large-scale implementation of SBIRT in PHC settings can yield substantial reductions of alcohol consumption in Germany. As high screening coverage rates may only be achievable in the long run, other effective alcohol policies are required to achieve short-term reduction of alcohol use and attributable harm in Germany. There is large potential to apply this open-access simulation model to other settings and for other alcohol interventions., Competing Interests: The authors have declared that no competing interests exist.

Background: As a policy option to reduce consumption of alcohol and the harm it does, on May 1, 2018, Scotland introduced a minimum price of 50 British pence (p) per unit of alcohol (8 g) sold; Wales followed suit on March 2, 2020, with the same minimum unit price (MUP). We analysed household purchase data based on bar codes to assess the impact of these policy options in the medium term for Scotland and in the immediate term for Wales., Methods: For these location-controlled, interrupted time series regression analyses, the data source was Kantar WorldPanel's household shopping panel, which, at the time of our analysis, included 35 242 British households providing detailed information on 1·24 million separate alcohol purchases in 2015-18 and the first half of 2020. With no data exclusions, we analysed the impact of introducing MUP in Scotland, using purchases in northern England as control, and in Wales, using western England as control. The studied changes associated with MUP were price paid per gram of alcohol purchased, grams of alcohol purchased, and amount of money spent on alcohol., Findings: In Scotland, price increases and purchase decreases following the introduction of MUP in 2018 were maintained during the first half of 2020. The difference between Scotland and northern England in 2020 was a price increase of 0·741 p per gram (95% CI 0·724-0·759), a 7·6% increase, and a purchase decrease of 7·063 g per adult per household per day that an alcohol purchase was made (6·656-7·470), a 7·7% decrease. In Wales, the introduction of MUP led to similar results. The difference between Wales and western England was a price increase 0·841 of 0·841 p per gram (0·732-0·951), an 8·2% increase, and a purchase decrease of 7·052 g per adult per household per day that an alcohol purchase was made (6·463-7·640), an 8·6% decrease. For both Scotland and Wales, reductions in overall purchases of alcohol were largely restricted to households that bought the most alcohol. The introduction of MUP was not associated with an increased expenditure on alcohol by households that generally bought small amounts of alcohol and, in particular, those with low incomes. The changes were not affected by the introduction of COVID-19 confinement in the UK on March 26, 2020., Interpretation: The evidence base supporting the positive, targeted impact of MUP is strengthened by the comparable results for Scotland and Wales. The short-term impact of MUP in Scotland during 2018 is maintained during the first half of 2020. MUP is an effective alcohol policy option to reduce off-trade purchases of alcohol and should be widely considered., Funding: None., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)