Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder.

AIMS: Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems. METHODS: We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N = 346). The Timeline Follow-back was used to assess WHO risk drinking level reductions and the Pittsburgh Sleep Quality Index was used to assess sleep quality over the prior month at baseline and the end of treatment. RESULTS: Sleep problem scores in the active medication and placebo groups improved equally. Fewer sleep problems were noted among individuals who achieved at least a 1-level reduction (B = -0.99, 95% confidence interval (CI) [-1.77, -0.20], P = .014) or at least a 2-level reduction (B = -0.80, 95% CI [-1.47, -0.14], P = .018) in WHO risk drinking levels at the end of treatment. Reductions in drinking, with abstainers excluded from the analysis, also predicted fewer sleep problems at the end of treatment (1-level: B = -1.01, 95% CI [-1.83, -0.20], P = .015; 2-level: B = -0.90, 95% CI [-1.59, -0.22], P = .010). CONCLUSIONS: Drinking reductions, including those short of abstinence, are associated with improvements in sleep problems during treatment for AUD. Additional assessment of the causal relationships between harm-reduction approaches to AUD and improvements in sleep is warranted.

Education and Training in Addiction Medicine and Psychology across Europe: A EUFAS Survey.

INTRODUCTION: Training in addiction medicine and addiction psychology is essential to ensure the quality of treatment for patients with substance use disorders. Some earlier research has shown varying training between countries, but no comprehensive study of addiction training across Europe has been performed. The present study by the European Federation for Addiction Societies (EUFAS) aimed to fill this gap. METHODS: A Delphi process was used to develop a questionnaire on specialist training in addiction treatment in 24 European countries. The final questionnaire consisted of 14 questions on either addiction medicine or addiction psychology, covering the nature and content of the training and institutional approval, the number of academic professorial positions, and the estimated number of specialists in each country. RESULTS: Information was not received from all countries, but six (Belgium, Denmark, Ireland, Italy, Poland, and Romania) reported no specialized addiction medicine training, while 17 countries did. Seven countries (Belgium, France, Ireland, Italy, Russia, Switzerland, and the Netherlands) reported no specialized addiction psychology training, while 14 countries did. Training content and evaluation methods varied. Approval was given either by governments, universities, or professional societies. Eighteen countries reported having professorships in addiction medicine and 12 in addiction psychology. The number of specialists in addiction medicine or psychology varied considerably across the countries. DISCUSSION: The survey revealed a large heterogeneity in training in addiction medicine and addiction psychology across Europe. Several countries lacked formal training, and where formal training was present, there was a large variation in the length of the training. Harmonization of training, as is currently the case for other medical and psychology specializations, is warranted to ensure optimal treatment for this under-served patient group.

Colocalization analysis of pancreas eQTLs with risk loci from alcoholic and novel non-alcoholic chronic pancreatitis GWAS suggests potential disease causing mechanisms.

BACKGROUND: Previous genome-wide association studies (GWAS) identified genome-wide significant risk loci in chronic pancreatitis and investigated underlying disease causing mechanisms by simple overlaps with expression quantitative trait loci (eQTLs), a procedure which may often result in false positive conclusions. METHODS: We conducted a GWAS in 584 non-alcoholic chronic pancreatitis (NACP) patients and 6040 healthy controls. Next, we applied Bayesian colocalization analysis of identified genome-wide significant risk loci from both, our recently published alcoholic chronic pancreatitis (ACP) and the novel NACP dataset, with pancreas eQTLs from the GTEx V8 European cohort to prioritize candidate causal genes and extracted credible sets of shared causal variants. RESULTS: Variants at the CTRC (p = 1.22 × 10-21) and SPINK1 (p = 6.59 × 10-47) risk loci reached genome-wide significance in NACP. CTRC risk variants colocalized with CTRC eQTLs in ACP (PP4 = 0.99, PP4/PP3 = 95.51) and NACP (PP4 = 0.99, PP4/PP3 = 95.46). For both diseases, the 95% credible set of shared causal variants consisted of rs497078 and rs545634. CLDN2-MORC4 risk variants colocalized with CLDN2 eQTLs in ACP (PP4 = 0.98, PP4/PP3 = 42.20) and NACP (PP4 = 0.67, PP4/PP3 = 7.18), probably driven by the shared causal variant rs12688220. CONCLUSIONS: A shared causal CTRC risk variant might unfold its pathogenic effect in ACP and NACP by reducing CTRC expression, while the CLDN2-MORC4 shared causal variant rs12688220 may modify ACP and NACP risk by increasing CLDN2 expression.

Association Between Functional and Structural Brain Connectivity of the Default Mode Network in Non-treatment Seeking Individuals With Alcohol Use Disorder.

AIMS: Alcohol use disorder (AUD) is associated with alterations within the default mode network (DMN) at rest. Also, impaired white matter structures have been observed in individuals with AUD. This study developed a workflow for examining the relation between functional and structural connectivity, exemplary for nodes of the DMN within a sample of non-treatment seeking individuals with AUD. Furthermore, AUD severity was correlated with both measures independently. METHODS: The functional magnetic resonance imaging (fMRI) protocol included anatomical, resting state and diffusion weighted imaging measurements. Independent component analyses and deterministic fiber tracking as well as correlation analyses, including the severity of AUD, were performed. N = 18 out of 23 adult study participants took part in the fMRI examination, and N = 15 were included in the final analyses. RESULTS: Established resting-state networks were reliably identified in our sample. Structural connections were found between several nodes of the DMN, whereas only fibers between the medial prefrontal cortex and the posterior cingulate cortex were reliably detected in all individuals. A negative correlation was observed between brain activation during rest and AUD severity in left parietal and temporal regions and the putamen. A more severe AUD predicted impairments in white matter integrity of the cingulum. CONCLUSION: In AUD, information obtained from a combination of resting-state, diffusion weighted data and clinical information has great potential to provide a more profound understanding of the disorder since alterations may already become apparent at earlier stages of the disorder, e.g. in non-treatment seeking individuals. SUMMARY: Alcohol use disorder leads to alterations in the default mode network of the resting brain that is associated with the severity of the disorder. Following our workflow, white matter impairments can be observed between some of the nodes of the default mode network using diffusion tensor imaging. Both, resting-state functional and structural connectivity relate to the severity of alcohol use disorder.

Stability of Drinking Reductions and Long-term Functioning Among Patients with Alcohol Use Disorder.

BACKGROUND: The World Health Organization (WHO) categorizes alcohol consumption according to grams consumed into low-, medium-, high-, and very-high-risk drinking levels (RDLs). Although abstinence has been considered the ideal outcome of alcohol treatment, reductions in WHO RDLs have been proposed as primary outcomes for alcohol use disorder (AUD) trials. OBJECTIVE: The current study examines the stability of WHO RDL reductions and the association between RDL reductions and long-term functioning for up to 3 years following treatment. DESIGN AND PARTICIPANTS: Secondary data analysis of patients with AUD enrolled in the COMBINE Study and Project MATCH, two multi-site, randomized AUD clinical trials, who were followed for up to 3 years post-treatment (COMBINE: n = 694; MATCH: n = 806). MEASURES: Alcohol use was measured via calendar-based methods. We estimated all models in the total sample and among participants who did not achieve abstinence during treatment. KEY RESULTS: One-level RDL reductions were achieved by 84% of patients at the end of treatment, with 84.9% of those individuals maintaining that reduction at a 3-year follow-up. Two-level RDL reductions were achieved by 68% of patients at the end of treatment, with 77.7% of those individuals maintaining that reduction at a 3-year follow-up. One- and two-level RDL reductions at the end of treatment were associated with significantly better mental health, quality of life (including physical quality of life), and fewer drinking consequences 3 years after treatment (p < 0.05), as compared to no change or increased drinking. CONCLUSION: AUD patients can maintain WHO RDL reductions for up to 3 years after treatment. Patients who had WHO RDL reductions functioned significantly better than those who did not reduce their drinking. These findings are consistent with prior reports suggesting that drinking reductions, short of abstinence, yield meaningful improvements in patient health, well-being, and functioning.

FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study.

Pharmacological treatment in alcohol use disorder suffers from modest effect sizes. Efforts have been undertaken to identify patient characteristics that help to select individuals that benefit from pharmacological treatment. Previous studies indicated that neural alcohol cue-reactivity (CR) might provide a marker that identifies patients, which benefit from naltrexone treatment.We investigated the reproducibility of the association between ventral striatum (VS) activation and naltrexone (NTX) treatment response by analyzing data from a recent longitudinal clinical trial in N = 44 abstinent treatment-seeking alcohol-dependent patients. A follow-up was conducted over 3 months. We computed the percentage of significant voxels in VS and tested main effects and interactions with NTX treatment on relapse risk using Cox Regression models.We found a significant interaction effect between pre-treatment cue reactivity in the VS and NTX treatment on time to first heavy relapse (Hazard Ratio = 7.406, 95% CI 1.17-46.56, p = 0.033), such that the patient group with high VS activation (defined by a mean split) showed a significant medication effect (Hazard Ratio = 0.140, 95% CI 0.02-0.75, p = 0.022) with a number needed to treat of 3.4 [95% CI 2.413.5], while there was no significant effect in the group with low VS activation (Hazard Ratio = 0.726, p = 0.454).Thus, using an independent sample we replicated the previously described positive association between VS activation and NTX efficacy. Although our results should be considered cautiously in light of the small sample size, our results support the potential of neural alcohol CR as a tool for precision medicine approaches in alcohol dependence.

Comparison of European Clinical Guidelines on the Management of Alcohol Use Disorders.

BACKGROUND: Alcohol is a leading cause of morbidity and mortality in the European region, and tackling the harmful use of alcohol is a public health priority. Most countries in the region have national strategies for treating alcohol use disorders (AUD), but there is significant between-country variation. OBJECTIVES: This study aimed to compare clinical guidelines for the management of AUD from countries of the European region and to determine whether countries' relative wealth or quality of their health systems had affected the guidelines. METHODS: A survey was conducted of 24 countries. The survey encompassed how AUD clinical guidelines were researched, the range and expertise of contributors, which topics of AUD treatment were included, the definition of a "standard drink" used, and the publishing, funding, endorsement, and dissemination of the guideline. RESULTS: Twenty-one of the 24 countries surveyed had a clinical guideline for AUD. All guidelines were underpinned by a literature review, and psychiatrists were the professional group most commonly involved in producing them. Most of the guidelines covered typical cornerstones of AUD care such as treatment of alcohol dependence, pharmacotherapy for relapse prevention, and detoxification. Definitions of a "standard drink" ranged from 8 to 20 grams of ethanol. Governments or governmental bodies were the main publishers and funders of guidelines, and the vast majority of guidelines were freely available online. There were no statistically significant effects of GDP, GDP per capita, or World Health Organization's World Health Report rankings on whether countries were more likely to have an AUD clinical guideline, to have performed a systematic literature review, or to have involved service users in producing their guideline. CONCLUSIONS: The results of this survey reflect widespread good practice in producing AUD clinical guidelines across European countries. Regional research collaborations could offer significant time and cost savings in producing the evidence base from which guidelines are then written.

Reduction in World Health Organization Risk Drinking Levels and Cardiovascular Disease.

BACKGROUND: Reductions in World Health Organization (WHO) risk drinking levels have recently been shown to lower the risk of multiple adverse health outcomes, but prior work has not examined reductions in WHO risk drinking levels in relation to cardiovascular disease (CVD), the leading cause of death for men and women in the United States and of global mortality. This study examined associations between reductions in WHO risk drinking levels and subsequent risk for CVD. METHODS: In a US national survey, 1,058 very-high-risk and high-risk drinkers participated in Wave 1 interviews (2001 to 2002) and Wave 2 follow-ups (2004 to 2005). Self-reported CVD history that was communicated to the participant by a doctor or other healthcare professionals included arteriosclerosis, hypertension, angina, tachycardia, or myocardial infarction. We used logistic regression to estimate adjusted odds ratios (aOR) evaluating relationships between ≥2-level reductions in WHO risk drinking levels from Wave 1 to Wave 2 and the risk of Wave 2 CVD, controlling for baseline characteristics. RESULTS: Reductions of ≥2 WHO risk drinking levels were associated with significantly lower odds of CVD in individuals who at Wave 1 were very-high-risk (aOR = 0.58 [0.41 to 0.80]) or high-risk drinkers (aOR = 0.81 [0.70 to 0.94]). Interaction terms showed that this relationship varied by age. Among individuals >40 years old at Wave 1, reductions of ≥2 WHO risk drinking levels were associated with significantly lower odds of CVD among very-high-risk drinkers (aOR = 0.42 [0.28 to 0.63]) but not high-risk drinkers (p = 0.50). Among individuals ≤40 years old at Wave 1, reductions of ≥2 WHO risk drinking levels were associated with significantly lower odds of CVD among high-risk drinkers (aOR = 0.50 [0.37 to 0.69]) but not very-high-risk drinkers (p = 0.27). CONCLUSIONS: These results show that reductions in WHO risk drinking levels are associated with reduced CVD risk among very-high-risk and high-risk drinkers in the US general population, and provide further evidence that reducing high levels of drinking provides important benefit across multiple clinical domains.

Neuropsychosocial profiles of current and future adolescent alcohol misusers.

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.

Incubation of neural alcohol cue reactivity after withdrawal and its blockade by naltrexone.

During the first weeks of abstinence, alcohol craving in patients may increase or "incubate." We hypothesize that Naltrexone (NTX) blocks this incubation effect. Here, we compared NTX effects on neural alcohol cue reactivity (CR) over the first weeks of abstinence and on long-term clinical outcomes to standard treatment. Male alcohol-dependent patients (n = 55) and healthy controls (n = 35) were enrolled. Participants underwent baseline psychometric testing and functional magnetic resonance imaging (fMRI) assessment of mesolimbic alcohol CR. Patients participated in a standard treatment program with the option of adjuvant NTX. They received another scan after 2 weeks of treatment. We found higher CR in several brain regions in patients versus healthy controls. CR significantly increased over 2 weeks in the standard treatment group (n = 13) but not in the NTX group (n = 22). NTX significantly attenuated CR in the left putamen and reduced relapse risk to heavy drinking within 3 months of treatment. Additionally, increased CR in the left putamen and its course over time predicted both NTX response and relapse risk. Carrier status for the functional OPRM1 variant rs1799971:A > G was considered but had no effect on NTX efficacy. In conclusion, NTX was most effective in patients with high CR in the left putamen. While the results from our naturalistic study await further confirmation from prospective randomized trials, they support a potential role of neural CR as a biomarker in the development of precision medicine approaches with NTX.

Advancing Precision Medicine for Alcohol Use Disorder: Replication and Extension of Reward Drinking as a Predictor of Naltrexone Response.

BACKGROUND: Precision medicine aims to identify those patients who will benefit the most from specific treatments. Recent work found large effects of naltrexone among "reward drinkers," defined as individuals who drink primarily for the rewarding effects of alcohol. This study sought to replicate and extend these recent findings by examining whether the desire to drink mediated the effect of naltrexone among reward drinkers. METHODS: We conducted a secondary analysis of a 12-week randomized clinical trial of daily or targeted naltrexone among problem drinkers (n = 163), with a focus on 86 individuals (n = 45 naltrexone and n = 41 placebo) who received daily medication. Interactive voice response technology was used to collect daily reports of drinking and desire to drink. Factor mixture models were used to derive reward and relief phenotypes. Moderation analyses were used to evaluate naltrexone effects, with phenotype as a moderator variable. Multilevel mediation tested average desire to drink as a mediator. RESULTS: Results indicated 4 phenotypes: low reward/low relief; low reward/high relief; high reward/low relief; and high reward/high relief. There was an interaction between the high reward/low relief subgroup (n = 10) and daily naltrexone versus placebo on drinks per drinking day (DPDD; p = 0.03), percent heavy drinking days (p = 0.004), and daily drinking (p = 0.02). As compared to placebo, individuals in the high reward/low relief phenotype who received daily naltrexone had significantly fewer DPDD (Cohen's d = 2.05) and had a lower proportion of heavy drinking days (Cohen's d = 1.75). As hypothesized, reductions in average desire to drink mediated the effect of naltrexone on average daily drinking among the high reward/low relief drinkers (moderated mediation effect: p = 0.029). CONCLUSIONS: This theory-driven study replicates the empirical finding that naltrexone is particularly efficacious among high reward/low relief drinkers. Our study brings the field a step closer to the potential of using a precision medicine approach to treating alcohol use disorder.

Maintenance of World Health Organization Risk Drinking Level Reductions and Posttreatment Functioning Following a Large Alcohol Use Disorder Clinical Trial.

BACKGROUND: Reductions in the World Health Organization (WHO) risk drinking levels have been proposed as an alternative primary outcome for alcohol clinical trials. Yet, little is known about whether reductions in WHO risk drinking levels can be maintained over time. The current study examined whether reductions in WHO risk drinking levels were maintained for up to 1 year following treatment, and whether reductions over time were associated with improvements in functioning. METHODS: Secondary data analysis of individuals with alcohol dependence (n = 1,226) enrolled in the COMBINE study, a multisite, randomized, placebo-controlled clinical trial. Logistic regression was used to examine the maintenance of end-of-treatment WHO risk level reductions and WHO risk level reductions at the 1-year follow-up. Repeated-measures mixed models were used to examine the association between WHO risk level reductions and functional outcomes over time. RESULTS: Achieving at least a 1- or 2-level reduction in risk by the end of treatment was significantly associated with WHO risk level reductions at the 1-year follow-up assessment (p < 0.001). Among individuals who achieved at least a 1-level reduction by the end of treatment, 85.5% reported at least a 1-level reduction at the 1-year follow-up. Among individuals who achieved at least a 2-level reduction by the end of treatment, 77.8% reported at least a 2-level reduction at the 1-year follow-up. WHO risk level reductions were associated with significantly lower alcohol consumption, better physical health (p < 0.01), and fewer alcohol-related consequences (p < 0.001) up to 1 year following treatment. CONCLUSIONS: One- and 2-level reductions in WHO risk levels during alcohol treatment were maintained after treatment and associated with better functioning over time. These findings support the use of the WHO risk level reductions as an outcome measure that reflects clinically significant improvement in how individuals seeking treatment for alcohol use disorder feel and function.

Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis.

OBJECTIVE: Alcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus. DESIGN: 1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used. RESULTS: We replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk. CONCLUSION: An inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.

Drinking Risk Level Reductions Associated with Improvements in Physical Health and Quality of Life Among Individuals with Alcohol Use Disorder.

BACKGROUND: Abstinence and no heavy drinking days are currently the only Food and Drug Administration-approved end points in clinical trials for alcohol use disorder (AUD). Many individuals who fail to meet these criteria may substantially reduce their drinking during treatment, and most individuals with AUD prefer drinking reduction goals. One- and two-level reductions in World Health Organization (WHO) drinking risk levels have been proposed as alternative end points that reflect reduced drinking and are associated with reductions in drinking consequences, improvements in mental health, and reduced risk of developing alcohol dependence. The current study examined the association between WHO drinking risk level reductions and improvements in physical health and quality of life in a sample of individuals with alcohol dependence. METHODS: Secondary data analysis of individuals with alcohol dependence (n = 1,142) enrolled in the longitudinal, prospective COMBINE study, a multi site randomized placebo-controlled clinical trial, examining the association between reductions in WHO drinking risk levels and change in blood pressure, liver enzyme levels, and self-reported quality of life following treatment for alcohol dependence. RESULTS: One- and two-level reductions in WHO drinking risk level during treatment were associated with significant reductions in systolic blood pressure (p < 0.001), improvements in liver enzyme levels (all p < 0.01), and significantly better quality of life (p < 0.001). CONCLUSIONS: One- and two-level reductions in WHO drinking risk levels predicted significant improvements in markers of physical health and quality of life, suggesting that the WHO drinking risk level reduction could be a meaningful surrogate marker of improvements in how a person "feels and functions" following treatment for alcohol dependence. The WHO drinking risk levels could be useful in medical practice for identifying drinking reduction targets that correspond with clinically significant improvements in health and quality of life.

Reduction in Nonabstinent WHO Drinking Risk Levels and Change in Risk for Liver Disease and Positive AUDIT-C Scores: Prospective 3-Year Follow-Up Results in the U.S. General Population.

BACKGROUND: Abstinence is often the treatment aim for alcohol use disorders (AUD), but this may deter individuals who prefer drinking reduction goals from entering treatment, and be an overly restrictive end point in alcohol clinical trials. Nonabstinent drinking reductions that predict improvement in how individuals feel or function may be useful clinical trial outcomes, for example, reductions in the 4-category World Health Organization (WHO) drinking risk levels. To investigate the clinical relevance of these reductions, we examined their relationship with 2 outcomes of interest to medical providers: liver disease, and positive scores on an alcohol screening measure. METHODS: Current drinkers in a U.S. national survey (n = 21,925) were interviewed in 2001 to 2002 (Wave 1) and re-interviewed 3 years later (Wave 2). WHO drinking risk levels, liver disease, and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) were assessed at both waves. Adjusted odds ratios (aORs) were used to indicate the association of change in WHO drinking risk levels with Wave 2 liver disease and AUDIT-C scores. RESULTS: Wave 1 very-high-risk drinkers who reduced 1, 2, or 3 WHO drinking risk levels had significantly lower odds of Wave 2 liver disease (aORs = 0.34, 0.23, 0.17) and positive AUDIT-C scores (aORs = 0.27, 0.09, 0.03). Wave 1 high-risk drinkers who reduced 1 or 2 WHO risk levels had significantly lower odds of positive AUDIT-C scores (aORs = 0.61, 0.25). Adjusting for alcohol dependence or AUDIT-C scoring variations did not affect results. CONCLUSIONS: In the highest-risk drinkers, reductions in WHO drinking risk levels predicted lower likelihood of liver disease and positive AUDIT-C scores. Results add to findings that reductions in the 4-category WHO drinking risk levels are a meaningful indicator of how individuals feel and function, and could serve as nonabstinent end points in clinical trials. Results also connect the WHO risk drinking levels to commonly used alcohol screening questions, which may be more familiar to healthcare providers.

Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level.

Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. ). A promising new medication for this population is sodium oxybate, a compound that acts on GABAB receptors and extrasynaptic GABAA receptors resulting in alcohol-mimetic effects. In this article, a European expert group of alcohol researchers and clinicians summarizes data (a) from published trials, (b) from two new-as yet unpublished-large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO-defined DRLs and (d) from multiple meta-analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol-dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25 years. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260 000 alcohol-dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well-tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol-dependent patients with VH DRL.

A Survey on the Medical Use of Cannabis in Europe: A Position Paper.

AIM: This study was aimed at investigating the availability and prescription of different medicinal variants of cannabis and their status in European countries. METHODS: A -web-based survey was sent to all member societies of the -European Federation of Addiction Societies (EUFAS) in 2 waves during the summer of 2017. All 34 member societies in 19 different European countries were invited to participate. RESULTS: We received 28 responses from 17 European countries. The cannabis extract nabiximol (Sativex®) is the most prevalent cannabis-based medicinal product marketed in Europe. Synthetic cannabinoids and standardized cannabis are less prevalent, and no country allows the growing of cannabis for personal medical use. The bringing of medical cannabis products from across borders to countries where the drug is not marketed is quite limited. The use of medical cannabis is restricted to some central medical conditions, but off-label use is prevalent in some countries. CONCLUSION: The use of medical cannabis in Europe seems to be restricted mostly to the use of the cannabis extract, nabiximol. There is only limited use of the cannabis plant as such for medical purposes, possibly indicating a different scenario in Europe as compared to the USA. Position Statement: EUFAS as an umbrella association of European addiction societies stresses the need for further studies on the efficacy of medical cannabis and warrants for possible dangers associated with the increasing popularity of medical cannabis. We need regulations at European level concerning registration and medical indications, development of uniform compounds and strength of products, and rules concerning sales and marketing.

Global Scientific Production on Illicit Drug Addiction: A Two-Decade Analysis.

AIMS: Addiction science has made great progress in the past decades. We conducted a scientometric study in order to quantify the number of publications and the growth rate globally, regionally, and at country levels. METHODS: In October 2015, we searched the Scopus database using the general keywords of addiction or drug-use disorders combined with specific terms regarding 4 groups of illicit drugs - cannabis, opioids, cocaine, and other stimulants or hallucinogens. All documents published during the 20-year period from 1995 to 2014 were included. RESULTS: A total of 95,398 documents were retrieved. The highest number of documents were on opioids, both globally (60.1%) and in each of 5 continents. However, studies on cannabis showed a higher growth rate in the last 5-year period of the study (2010-2014). The United States, the United Kingdom, Germany, Canada, Australia, France, Spain, Italy, China, and Japan - almost all studies were from high-income countries - occupied the top 10 positions and produced 81.4% of the global science on drug addiction. CONCLUSION: As there are important socio-cultural differences in the epidemiology and optimal clinical care of addictive disorders, it is suggested that low- and more affected middle-income countries increase their capacity to conduct research and disseminate the knowledge in this field.

[Health Care Organization - The New German S3-Guideline on Alcohol-Related Disorders and its Relevance for Health Care]. / Versorgungsorganisation ­ Die neue S3-Leitlinie Alkohol und ihre Bedeutung für die Versorgungspraxis.

BACKGROUND: Alcohol dependence is one of the most serious diseases of addiction in Germany. The new S3-guideline "Screening, Diagnostics and Treatment of Alcohol-Related Disorders" has been presented in 2015 and summarizes the present state of knowledge pertaining to the diagnosis and treatment of alcohol abuse and alcohol dependence. METHODS: This guideline was developed over four years within the framework of the Association of the Scientific Medical Societies in Germany (AWMF). The German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) and the German Society for Research and Therapy in Addiction (DG-Sucht) took the lead in the organization. More than 50 professional societies and associations and health organizations as well as more than 60 acknowledged experts were involved, including networks of self-help groups and relatives. The working group on "health care organization", whose results are presented here, was one out of thirteen working groups, focusing on the task how to implement the guideline under the basic conditions of the German health care system with its sectors and interfaces. RESULTS: For the chapter on "health care organization" 27 recommendations have been consented. Many of these have been prepared by the respective working groups. These recommendations cover areas such as screening, diagnostics and short interventions, detoxification and withdrawal as well as pharmacotherapy, physical complications and psychic comorbidity, medical rehabilitation and other forms of post-acute treatment, primary care by general practitioners, as well as specific target groups such as children and adolescents, (pregnant) women and the elderly, and, in addition, self-help approaches. CONCLUSION: For needs-based diagnostics and treatment of alcohol-related disorders, guideline-based recommendations for health care organization offer a framework for the cooperation and coordination of all health sectors and occupational groups, especially with respect to their interfaces. This includes the cooperation between the medical and the psychosocial system and stretches from harm reduction to social inclusion of people concerned. Particularly the field of rehabilitation with its explicit aims for participation relies heavily on such a cooperation.