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This study explores sociocultural differences in alcohol-related impact on quality of life between France and United Kingdom. We included 38 alcohol-dependent patients in France and United Kingdom in 10 focus groups. We used a text-mining approach. Three classes of each corpus regarded identical themes across the countries: (a) core impact on quality of life, (b) drinking habits, (c) sources of help. Core impact was similar between the two countries. Main differences were in drinking habits and referral to sources of help. Despite differences in drinking habits, the domains of life impacted by alcohol were non-country specific.

Background: Hazardous and harmful alcohol use and high blood pressure are central risk factors related to premature non-communicable disease (NCD) mortality worldwide. A reduction in the prevalence of both risk factors has been suggested as a route to reach the global NCD targets. This study aims to highlight that screening and interventions for hypertension and hazardous and harmful alcohol use in primary healthcare can contribute substantially to achieving the NCD targets., Methods: A consensus conference based on systematic reviews, meta-analyses, clinical guidelines, experimental studies, and statistical modelling which had been presented and discussed in five preparatory meetings, was undertaken. Specifically, we modelled changes in blood pressure distributions and potential lives saved for the five largest European countries if screening and appropriate intervention rates in primary healthcare settings were increased. Recommendations to handle alcohol-induced hypertension in primary healthcare settings were derived at the conference, and their degree of evidence was graded., Results: Screening and appropriate interventions for hazardous alcohol use and use disorders could lower blood pressure levels, but there is a lack in implementing these measures in European primary healthcare. Recommendations included (1) an increase in screening for hypertension (evidence grade: high), (2) an increase in screening and brief advice on hazardous and harmful drinking for people with newly detected hypertension by physicians, nurses, and other healthcare professionals (evidence grade: high), (3) the conduct of clinical management of less severe alcohol use disorders for incident people with hypertension in primary healthcare (evidence grade: moderate), and (4) screening for alcohol use in hypertension that is not well controlled (evidence grade: moderate). The first three measures were estimated to result in a decreased hypertension prevalence and hundreds of saved lives annually in the examined countries., Conclusions: The implementation of the outlined recommendations could contribute to reducing the burden associated with hypertension and hazardous and harmful alcohol use and thus to achievement of the NCD targets. Implementation should be conducted in controlled settings with evaluation, including, but not limited to, economic evaluation.

Abstinence from alcohol has been the prevailing treatment goal for individuals with alcohol dependence (AD) within the context of specialty alcohol treatment. Yet, alcohol use has been conceptualized as existing on a continuum. Importantly, most people who meet criteria for AD and could benefit from treatment never receive treatment. About half of these individuals do not seek treatment because they report a desire to continue drinking. To increase acceptability of treatment, reductions in alcohol consumption have been examined as alternative outcomes in treatment trials for AD. The current study reviews data which indicate that long-term reduction in alcohol consumption among patients with AD is possible. Controlled studies have tested reduced alcohol consumption and show sustained improvements in drinking reductions for many patients following behavioral treatments and pharmacotherapy. Evidence-based treatment guidelines and medicines development guidance authorities have taken note of these developments and accept "intermediate harm reduction" (European Medicines Agency) or "low-risk drinking limits" (US Federal Drug Administration) as optional trial endpoints. In conclusion, while abstinence remains the safest treatment goal for individuals with AD, evidence supports that reduced drinking approaches may be an important extension in the treatment of AD., (© 2017 S. Karger AG, Basel.)

Background: The objective of this article was to investigate the effect of as-needed nalmefene on health-related quality of life (HRQoL) in patients with alcohol dependence, and to relate changes in drinking behavior and status to HRQoL outcomes., Methods: This post hoc analysis was conducted on a pooled subgroup of patients with at least a high drinking risk level (men: >60 g/day; women: >40 g/day) who participated in one of two randomized controlled 6-month studies, ESENSE 1 and ESENSE 2. Patients received nalmefene 18 mg or placebo on an as-needed basis, in addition to a motivational and adherence-enhancing intervention (BRENDA). At baseline and after 12 and 24 weeks questionnaires for the Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36), European Quality of life-5 Dimensions (EQ-5D) and the Drinker Inventory of Consequences (DrInC-2R) were completed., Results: The pooled population consisted of 667 patients (nalmefene: 335; placebo: 332), with no notable between-group differences in baseline patient demographics/characteristics. At week 24, nalmefene had a superior effect compared to placebo in improving SF-36 mental component summary scores (mean difference [95% CI], p-value: 3.09 [1.29, 4.89]; p=0.0008), SF-36 physical component summary scores (1.23 [0.15, 2.31]; p=0.026), EQ-5D utility index scores (0.03 [0.00, 0.06]; p=0.045), EQ-5D health state scores (3.46 [0.75, 6.17]; p=0.012), and DrInC-2R scores (-3.22 [-6.12, 0.33]; p=0.029). The improvements in SF-36 mental component summary scores at week 24, and the DrInC-2R total score change from baseline to week 24, were significantly correlated to reductions in heavy drinking days and total alcohol consumption at week 24., Conclusions: As-needed nalmefene significantly improved almost all patient-reported HRQoL measures included in SF-36 and EQ-5D compared with placebo. These HRQoL gains were significantly correlated to reduced drinking behavior, as determined by reductions in heavy drinking days and total alcohol consumption.

Background: European Medicines Agency guidelines recognize two different treatment goals for alcohol dependence: abstinence and reduction in alcohol consumption. All currently approved agents are indicated for abstinence. This systematic review aimed to identify drugs in development for alcohol dependence treatment and to establish, based upon trial design, if any are seeking market authorization for reduction in consumption., Methods: We searched PubMed and Embase (December 2001-November 2011) to identify agents in development for alcohol dependence treatment. Additional studies were identified by searching ClinicalTrials.gov and the R&D Insight and Clinical Trials Insight databases. Studies in which the primary focus was treatment of comorbidity, or n≤20, were excluded. Studies were then classified as 'abstinence' if they: described a detoxification/alcohol withdrawal period; enrolled patients who had undergone detoxification previously; or presented relapse/abstinence rates as the primary outcome. Studies in patients actively drinking at baseline were classified as 'reduction in consumption'., Results: Of 602 abstracts identified, 45 full-text articles were eligible. Five monotherapies were in development for alcohol dependence treatment: topiramate, fluvoxamine, aripiprazole, flupenthixol and nalmefene. Nalmefene was the only agent whose sponsor was clearly seeking definitive approval for reduction in consumption. Development status was unclear for topiramate, fluvoxamine, aripiprazole and flupenthixol. Fifteen agents were examined in published exploratory investigator-initiated trials; the majority focused on abstinence. Ongoing (unpublished) trials tended to focus on reduction in consumption., Conclusions: While published studies generally focused on abstinence, ongoing trials focused on reduction in consumption, suggesting a change in emphasis in the approach to treating alcohol dependence., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aims: The aim of the study was to investigate the efficacy and safety of as-needed use of nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment, i.e. the pooled subgroup of patients with at least a high drinking risk level (men: >60 g/day; women: >40 g/day) at both screening and randomization from the two randomized controlled 6-month studies ESENSE 1 (NCT00811720) and ESENSE 2 (NCT00812461)., Methods: Nalmefene 18 mg and placebo were taken on an as-needed basis. All the patients also received a motivational and adherence-enhancing intervention (BRENDA). The co-primary outcomes were number of heavy drinking days (HDDs) and mean total alcohol consumption (g/day) in Month 6 measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study., Results: The pooled population consisted of 667 patients: placebo n = 332; nalmefene n = 335. There was a superior effect of nalmefene compared with placebo in reducing the number of HDDs [treatment difference: -3.2 days (95% CI: -4.8; -1.6); P < 0.0001] and total alcohol consumption [treatment difference: -14.3 g/day (-20.8; -7.8); P < 0.0001] at Month 6. Improvements in clinical status and liver parameters were greater in the nalmefene group compared with the placebo group. Adverse events and adverse events leading to dropout were more common with nalmefene than placebo., Conclusion: As-needed nalmefene was efficacious in reducing alcohol consumption in patients with at least a high drinking risk level at both screening and randomization, and the effect in this subgroup was larger than in the total population.

Rationale: Little is known about the effect of disulfiram on subjective and autonomic nervous system cue reactivity in the laboratory. The dissuasive psychological effect manifested as a threat would seem to prevail over the pharmacological effect., Objectives: The primary objective was to determine whether there was a difference in cue reactivity responses during a threat condition compared to a neutral condition during alcohol cue exposure., Methods: In a crossover randomized study, participants received threat and neutral messages during two cue exposure sessions. The threat condition consisted of leading the patients to believe they had ingested 500 mg of disulfiram and the neutral condition of informing them that they had ingested a placebo, while in both condition they received the same placebo., Results: Physiological cue reactivity was demonstrated by a decrease in diastolic blood pressure during the threat compared to the neutral condition (p=0.04). Heart rate and subjective cue reactivity measures remained unchanged. There was a negative affect (assessed by the Positive and Negative Affect Scale) by condition by exposure interaction., Conclusions: The threat of a disulfiram-ethanol reaction appears to affect cue reactivity physiologically rather than subjectively. While the data does not show changes in subjective ratings, it is possible that there are alternative beneficial effects arising from other cognitive processes that are not captivated by self-reported craving scales, reflected by decreases in negative affect and blood pressure. From this perspective, disulfiram might be recast to be more acceptable to patients., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The health effects of alcohol consumption, particularly regarding potential protective benefits of light to moderate intake compared to abstinence, remain a subject of ongoing debate. However, epidemiological studies face limitations due to imprecise exposure measurements and the potential for bias through residual confounding and reverse causation. To address these limitations, we conducted a systematic review of Mendelian Randomization (MR) studies examining the causal relationship between alcohol consumption and cancers, cardiovascular, liver, and neurological diseases. Methodology: We searched PubMed, ScienceDirect and Embase and Europe PMC up to 05/2024 for MR studies investigating the association of genetically predicted alcohol consumption with cancers, cardiovascular, liver and neurological diseases. We assessed methodological quality based on key elements of the MR design a genetic association studies tool. Results: We included 70 MR studies that matched our inclusion criteria. Our review showed a significant association of alcohol consumption with multiple cancers such as oral and oropharyngeal, esophageal, colorectal cancers, hepatocellular carcinoma and cutaneous melanoma. While the available studies did not consistently confirm the adverse or protective effects of alcohol on other cancers, such as lung cancer, as suggested by observational studies. Additionally, MR studies confirmed a likely causal effect of alcohol on the risk of hypertension, atrial fibrillation, myocardial infraction and vessels disease. However, there was no evidence to support the protective effects of light to moderate alcohol consumption on cognitive function, Alzheimer's disease, and amyotrophic lateral sclerosis, as reported in observational studies while our review revealed an increased risk of epilepsy and multiple sclerosis. The available studies provided limited results on the link between alcohol consumption and liver disease. Conclusions: Despite the valuable insights into the causal relationship between alcohol consumption and various health outcomes that MR studies provided, it is worth noting that the inconsistent ability of genetic instrumental variables to distinguish between abstainers, light and moderate drinkers makes it difficult to differentiate between U or J-shaped vs. linear relationships between exposure and outcome. Additional research is necessary to establish formal quality assessment tools for MR studies and to conduct more studies in diverse populations, including non-European ancestries. Systematic Review Registration: www.crd.york.ac.uk/prospero/display%5frecord.php?ID=CRD42021246154 , Identifier: PROSPERO (CRD42021246154). [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the validity of World Health Organization (WHO) risk drinking level reductions as meaningful endpoints for clinical practice and research. This study examined whether such reductions were associated with a lower likelihood of a current alcohol use disorder (AUD) diagnosis and fewer AUD criteria. Methods: We conducted a secondary data analysis to address these objectives using data from a multisite randomized controlled trial of gabapentin enacarbil extended release in treating moderate to severe AUD among adults (N = 346). Participants received gabapentin enacarbil extended release or placebo for 6 months. The timeline follow-back was used to assess WHO risk drinking level reductions, and the Mini-International Neuropsychiatric Interview was used to assess Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria at baseline (past year) and end of treatment (past month). Results: Most participants (80.1%) achieved at least a 1-level reduction in the WHO risk drinking levels from baseline to end of treatment, and nearly half of participants (49.8%) achieved at least a 2-level reduction. At least a 1-level reduction or at least a 2-level reduction in WHO risk drinking level predicted lower odds of an active AUD diagnosis (1-level: odds ratio, 0.74 [95% confidence interval (CI), 0.66–0.84]; 2-level: odds ratio, 0.71 [95% CI, 0.64–0.79]) and fewer AUD criteria (1-level: B, −1.66 [95% CI, −2.35 to −0.98]; 2-level: B, −1.76 [95% CI, −2.31 to −1.21]) at end of treatment. Conclusions: World Health Organization risk drinking level reductions correlate with Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria, providing further evidence for their use as endpoints in alcohol intervention trials, which has potential implications for broadening the base of AUD treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Abstinence has historically been considered the preferred goal of alcohol use disorder (AUD) treatment. However, most individuals with AUD do not want to abstain and many are able to reduce their drinking successfully. Craving is often a target of pharmacological and behavioral interventions for AUD, and reductions in craving may signal recovery. Whether reductions in drinking during AUD treatment are associated with reductions in craving has not been well examined. Methods: We conducted secondary analyses of data from three AUD clinical trials (N's= 1327, 346, and 200). Drinking reductions from baseline to the end of treatment were measured as changes in World Health Organization (WHO) risk drinking levels; alcohol craving was measured using validated self‐report measures. Regression analyses tested whether drinking reductions were associated with end‐of‐treatment craving reductions; moderation analyses tested whether associations between drinking reduction and end‐of‐treatment craving differed across AUD severity. Results: Reductions of at least 1 or at least 2 WHO risk drinking levels were associated with lower craving (all p's < 0.05). Results were substantively similar after removing abstainers at the end‐of‐treatment. Associations between drinking reductions and craving were generally not moderated by AUD severity. Conclusions: Individuals with WHO risk drinking level reductions reported significantly lower craving, as compared to those who did not achieve meaningful reductions in drinking. The results demonstrate the utility of WHO risk drinking levels as AUD clinical trial endpoints and provide evidence that drinking reductions mitigate craving. [ABSTRACT FROM AUTHOR]

Excessive alcohol consumption is the leading cause of liver diseases in Western countries, especially in France. Alcohol‐related liver disease (ARLD) is an extremely broad context and there remains much to accomplish in terms of identifying patients, improving prognosis and treatment, and standardising practices. The French Association for the Study of the Liver wished to organise guidelines together with the French Alcohol Society in order to summarise the best evidence available about several key clinical points in ARLD. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe how patients with ARLD should be managed nowadays and discuss the main unsettled issues in the field. [ABSTRACT FROM AUTHOR]

Aims Two complementary studies were used to assess the real-life use of nalmefene in alcohol-dependent patients and its impact on alcohol use health status. Methods USE-PACT was a prospective cohort study designed to evaluate the real-life effectiveness of nalmefene in the management of alcohol dependence, as assessed by total alcohol consumption (TAC) and number of heavy drinking days (HDD) at 1 year. USE-AM was a cohort study using data from the French nationwide claims database and was used to evaluate the external validity of the population in the prospective study. Results Overall, 256 of 700 new nalmefene users enrolled in the USE-PACT study had valid data at 1 year. After 1 year, patients treated with nalmefene showed a mean ± SD reduction from baseline in TAC (−41.5 ± 57.4 g/day) and number of HDD (−10.7 ± 11.7 days/4 weeks). Patients took a mean ± SD of 20.0 ± 12.0 tablets/4 weeks (median of 1 tablet/day) for the first 3 months and then reduced the dose. The proportion of patients who no longer took nalmefene gradually increased from 5% at 1 month to 52% at 1 year. The USE-AM study identified 486 patients with a first reimbursement for nalmefene in 2016; baseline characteristics confirmed external validity of the USE-PACT study. Overall, 46.3% of initial USE-AM prescriptions were made by GPs; most (91.8%) patients stopped treatment during follow-up. However, 15.2% of patients resumed treatment after stopping. Conclusions In this analysis of French routine practice, patients with alcohol dependence treated with nalmefene showed reduced alcohol consumption, and nalmefene was generally well tolerated. [ABSTRACT FROM AUTHOR]

Introduction: The objective for this study was to combine drinking characteristics and two subjective measures, drinker identity and alcohol-related quality of life, i.e., negative impact of alcohol on quality of life, to determine relevant profiles for indicated prevention programs. In particular, we hypothesized that different profiles of students with high level of alcohol consumption exist when exploring subjectivity.Methods: We performed an online survey among 16,930 students. We collected sociodemographics and environmental data, including alcohol-related quality of life, drinker identity, and drinking characteristics. We performed a hierarchical clustering on principal components. We described all variables in each cluster and explored between clusters differences by Kruskal-Wallis tests.Results: We identified five clusters as regarding drinker identity, drinking characteristics, and alcohol-related quality of life. Among these five clusters, three clusters presented high drinking characteristics. A very vulnerable cluster showed high level of alcohol consumption, impact on quality of life and on academic results, and strong drinker identity. An egodystonic cluster showed high level of consumption, mild impact on quality of life and on academic results, but low drinker identity. A cluster seemed short-term super-adapted in heavy drinking environment, showing high level of alcohol consumption and drinker identity, but low impact on quality of life and on academic results (all between clusters p values < 0.001 with Kruskal-Wallis tests).Conclusion: The subjective experience of students from these clusters was significantly different (p value < 0.001), and could explain some inadequacy of certain prevention strategies, considering binge drinker student as a homogeneous group. Prospective studies are needed to explore changes over time of these clusters. [ABSTRACT FROM AUTHOR]

Aims Alcohol dependence is a major public health issue with a need for new pharmacological treatments. The ALPADIR study assessed the efficacy and safety of baclofen at the target dose of 180 mg/day for the maintenance of abstinence and the reduction in alcohol consumption in alcohol-dependent patients. Methods Three hundred and twenty adult patients (158 baclofen and 162 placebo) were randomized after alcohol detoxification. After a 7-week titration, the maintenance dose was provided for 17 weeks, then progressively decreased over 2 weeks before stopping. Results The percentage of abstinent patients during 20 consecutive weeks (primary endpoint) was low (baclofen: 11.9%; placebo: 10.5%) and not significantly different between groups (OR 1.20; 95%CI: 0.58 to 2.50; P = 0.618). A reduction in alcohol consumption was observed from month 1 in both groups, but the difference of 10.9 g/day at month 6 between groups, in favour of baclofen, was not statistically significant (P = 0.095). In a subgroup of patients with high drinking risk level at baseline, the reduction was greater with a difference at month 6 of 15.6 g/day between groups in favour of baclofen (P = 0.089). The craving assessed with Obsessive-Compulsive Drinking Scale significantly decreased in the baclofen group (P = 0.017). No major safety concern was observed. Conclusions This study did not demonstrate the superiority of baclofen in the maintenance of abstinence at the target dose of 180 mg/day. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen. Short summary Baclofen was assessed versus placebo for maintenance of abstinence and reduction in alcohol consumption in alcohol-dependent patients. This study did not demonstrate the superiority of baclofen in the maintenance of abstinence. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen. [ABSTRACT FROM AUTHOR]

Alcohol use disorder is a major public health issue. The absolute mortality burden of alcohol-attributable death has increased over the last 20 years. However, access to care remains very poor and many people with alcohol use disorder are untreated. The main limiting factor for access to care in alcohol use disorder appears to be the reluctance to engage in abstinence. Risk reduction is a developing approach in the treatment of alcohol use disorders, drawing its inspiration, with quite a delay, from the decades-long dominant approach in other substance use disorders. A paradigm shift has recently occurred that places more of an emphasis on reducing alcohol as a therapeutic strategy for patients with alcohol use disorder, to better meet the patients' preferences and needs. The development and recent approval of nalmefene, in alcohol-dependent adults with a high drinking risk level, contributes to enlarging the therapeutic arsenal for alcohol dependence, strengthening the legitimacy of alcohol reduction strategies. [ABSTRACT FROM AUTHOR]

Background:  Some studies have reported that the A9 allele of the variable nucleotide tandem repeat (VNTR) of the gene which encodes the dopamine transporter ( DAT1/SLC6A3) is associated with alcoholism withdrawal symptoms such as alcohol withdrawal seizures (WSs), whereas others did not. We investigated whether polymorphisms within the DAT1 gene are associated with WS taking into account some of the confounding factors such as the severity of alcohol dependence. Methods:  To further assess the role of this gene in WS, we genotyped the VNTR and 7 single nucleotide polymorphisms (SNPs) encompassing the DAT1 gene in a sample of 250 alcohol-dependent subjects (175 men and 75 women), of whom 24% exhibited WSs, taking into account the severity of alcohol dependence. Results:  The VNTR is associated with an increased risk of WSs (odd ratio = 3.5; p = 0.019), even when controlling for confounding factors ( p = 0.031). As 2 SNPs, in roughly the same location of the gene (namely rs27072 and rs27048), are also associated with WSs, it is possible that the initial association of the VNTR polymorphism was tagging a specific haplotype of this gene. Indeed, in our sample of alcohol-dependent patients, 2 haplotypes were associated with a significantly different risk of WSs. Conclusions:  The present study adds evidence for a significant role of the 3′ part of the DAT1 gene in WS of alcohol-dependent patients, not only because it is in accordance with previous work, but also because of larger statistical power (as relying on a sample over sampled with the studied phenotype), as it gives a more precise analysis of different SNPs within the DAT1 gene, and as it confirms the association when major potentially confounding factors are taken into account in a logistical regression analysis. [ABSTRACT FROM AUTHOR]