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Background: Addressing the limited access to treatments for alcohol dependence, we developed ALM-002, a therapeutic application to be "prescribed" for non-abstinence-oriented treatment in internal medicine settings. Our objective was to preliminarily assess the efficacy and safety of ALM-002., Methods: In a multicenter, open-label randomized controlled trial, participants aged ≥20 with alcohol dependence and daily alcohol consumption exceeding 60 g for men and 40 g for women, without severe complications, were randomly assigned to either the intervention group using ALM-002 or the treatment-as-usual control group. Participant in both groups received individual face-to-face sessions by physicians at weeks 0, 4, 8, and 12. The primary endpoint was the change in heavy drinking days (HDDs) from week 0 to week 12. A mixed model for repeated measures was employed., Results: We enrolled 43 participants: 22 in the intervention group and 21 in the control group. A significant reduction in HDDs every 4 weeks from week 0 to week 12 was observed, with a between-group difference of -6.99 days (95% CI: -12.4 to -1.6 days, standardized mean difference: -0.80)., Conclusions: These results indicate the potential of ALM-002 as a viable treatment for alcohol dependence. Further studies are needed to evaluate the clinical potential of ALM-002., Competing Interests: Declaration of competing interest RS reports personal fees from CureApp, Inc., during the conduct of the study; grants from Osake-no-Kagaku Foundation, grants from The Mental Health Okamoto Memorial Foundation, grants from Kobayashi Magobe Memorial Medical Foundation, personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Nippon Shinyaku Co., Ltd., personal fees from Takeda Pharmaceutical Co., Ltd., outside the submitted work; In addition, RS has a patent JP2022049590A, US20220084673A1 pending, a patent JP2022178215A pending, a patent JP2022070086 pending, and a patent JP2023074128A pending. YI, TY received a research funding from CureApp Inc. outside the submitted work. SMa and KN received personal fees for coordinating a pivotal study from Cure App Inc. outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: In Japan, paper-based surveys are currently more effective than web-based surveys. This study compared the response rates and lifestyle behaviors between paper- and web-based surveys conducted among Japanese junior and senior high schools., Methods: In total, there were 42 and 64 junior and senior high schools, respectively, for the web-based surveys and 20 and 27 junior and senior high schools, respectively, for the paper-based surveys. The questionnaire covered lifestyle behaviors (e.g., alcohol consumption, smoking, exercise, eating, and sleep status), mental health, and plans to attend college. School- and student-level response rates by survey method were assessed, and so was the effect on the reporting of each lifestyle behavior using logistic regression models., Results: The school response rates were 16.0% and 38.3% for web- and paper-based surveys, respectively. The student response rates were 88.7% and 77.2%, respectively. The web-based group had significantly more female participants and lower response rates for higher grades in senior high schools. The odds of lifetime and current alcohol consumption and poor mental health were lower, whereas those of lifetime use of conventional cigarettes, shorter sleep duration, and plans to continue attending college were higher among web-based (vs. paper-based) participants., Conclusions: The school response rate was poor in the web-based survey. However, whether the differences in lifestyle behavior are attributed to selection bias or the survey method remains unclear., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

Importance: Secondhand smoke is a substantial risk factor for youth health globally, including in Japan, where tobacco control policies should be reassessed., Objective: To assess trends in the prevalence of secondhand smoke exposure among Japanese adolescents from 2008 to 2017 and to examine the association between its frequency and smoking during the study period., Design, Setting, and Participants: This study comprised a nationally representative, self-administered, school-based, cross-sectional survey focusing on tobacco and alcohol use and related factors among students in grades 7 to 12 (ages 12-18 years) in Japan. This random sampling survey used single-stage cluster sampling. Using the national school directory, junior and senior high schools throughout Japan were randomly extracted from each regional block. All students enrolled in the sampled schools were included as participants, and school-based surveys were completed in 2008, 2012, and 2017. Data analysis was performed from January 1 to March 15, 2023., Main Outcomes and Measures: Prevalence of secondhand smoke exposure among adolescents in Japan from 2008 to 2017 and changes in the association between secondhand smoke exposure frequency and prevalence of smoking were examined using multiple logistic regression analysis., Results: Data were analyzed for 95 680 adolescents in 2008 (50.7% boys), 100 050 in 2012 (51.6% boys), and 64 152 in 2017 (53.9% boys). At baseline, 42.0%, 38.5%, and 34.6% of the participants were junior high school students in 2008, 2012, and 2017, respectively. Based on the 2008 surveys, 51.0% of adolescents in grades 7 to 12 were exposed to secondhand smoke in any place (≥1 day during the past 7 days), 37.2% were exposed at home, and 36.5% were exposed in public places. In 2017, 36.3% of participants were exposed to secondhand smoke in any place, 23.8% were exposed at home, and 27.0% were exposed in public places. An association between secondhand smoke exposure frequency and prevalence of smoking was observed consistently regardless of survey year, location, or pattern of exposure (adjusted odds ratios ranged from 2.29 [95% CI, 1.81-2.91] for 1-2 days at home to 11.15 [95% CI, 8.50-14.62] for 7 days in public places). Stratified analysis by higher education intention indicated that the prevalence of smoking and secondhand smoke exposure decreased but remained higher among adolescents who did not intend to pursue higher education. The association between secondhand smoke and smoking did not differ substantially between groups., Conclusions and Relevance: In this cross-sectional study, the prevalence of secondhand smoke exposure among adolescents in Japan decreased but remained at high levels overall. There may not be a hazard-free threshold for smoking. Enhancing comprehensive tobacco control strategies is Japan's first step toward achieving smoke-free environments to protect youths. Implementation and verification of the effectiveness of smoke-free legislation should be considered.

Background: Growing evidence suggests that intervention for smoking cessation enhances alcohol abstinence in treatment settings for alcohol dependence. However, research in this field is rare in Asians., Method: We prospectively investigated the association of smoking status with drinking status using 9 surveys mailed during a 12-month period in 198 Japanese alcohol-dependent men (70 never/ex-smokers and 128 smokers) who admitted for the first time and completed a 3-month inpatient program for simultaneous alcohol abstinence and smoking cessation., Results: Nonsmoking during the first month after discharge and at the end of follow-up was reported in 28.9% and 25.0% of the baseline smokers, respectively. Kaplan-Meier estimates showed that a 12-month alcohol abstinence and heavy-drinking-free status were more frequent among never/ex-smokers (45.1% and 59.8%, respectively) and baseline smokers who quit smoking during the first month after discharge (59.0% and 60.8%, respectively), compared with sustained smokers (30.0% and 41.2%, respectively). Among the baseline smokers, the multivariate odds ratio (95% confidence interval) for smoking cessation during the first month were 2.77 (1.01-7.61) for alcohol abstinence during the period and 2.50 (1.00-6.25) for use of varenicline, a smoking cessation agent, during the inpatient program. After adjusting for age, drinking profile, lifestyle, family history of heavy or problem drinking, lifetime episodes of other major psychiatric disorders, and medications at discharge, the multivariate hazard ratios (HRs) for drinking lapse were 0.57 (0.37-0.89) for the never/ex-smoking and 0.41 (0.23-0.75) for new smoking cessation groups, respectively, compared with sustained smoking, while the corresponding HRs for heavy-drinking lapse were 0.55 (0.33-0.90) and 0.47 (0.25-0.88), respectively. The HR for drinking lapse was 0.63 (0.42-0.95) for the nonsmoking group (vs. smoking) during the observation period, while the HR for heavy-drinking lapse was 0.58 (0.37-0.91) for the nonsmoking group (vs. smoking) during the observation period. Other significant variables that worsened drinking outcomes were higher daily alcohol intake prior to hospitalization, family history of heavy or problem drinking and psychiatric medications at discharge., Conclusion: Nonsmoking was associated with better outcomes on the drinking status of Japanese alcohol-dependent men, and a smoking cessation program may be recommended to be integrated into alcohol abstinence programs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yokoyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: No study in Japan has investigated alcohol's harm to others (AHTO). Therefore, this study aimed to reveal the situation of AHTO in Japan and examine the factors associated with it based on the relationship with the drinker., Methods: A cross-sectional population-based survey was performed in 2018 with 2121 men and 2507 women. Respondents were asked questions about factors such as verbal or physical aggression, being forced to drink alcohol, sexual harassment and their relationship with the drinker. Binomial logistic regression was performed to quantify the associations of AHTO with participants' socio-demographic status and drinking patterns., Results: The lifetime experience of AHTO was 24.7% for men and 19.3% for women. AHTO from the father and co-workers were the most common in and outside the home, respectively. The frequency of AHTO from the spouse or co-workers showed no significant difference for abstainers and drinkers. However, AHTO from the father was more commonly reported among drinkers and those with Alcohol Use Disorders Identification Test scores ≥8 points than abstainers. Of those who experienced AHTO, 24.5% of men and 27.6% of women, and 6.1% of men and 12.9% of women were profoundly affected by it in and outside the home, respectively., Discussion and Conclusions: One in five Japanese residents experienced AHTO in their life, and the characteristics associated with AHTO differed according to the affected individual's relationship with the drinker. Continued monitoring of AHTO and measures aimed at reducing alcohol-related harm that include AHTO should be promoted., (© 2022 Australasian Professional Society on Alcohol and other Drugs.)

Background: Underage drinking is a public health concern. However, few studies have examined the association between alcoholic beverage advertising and underage drinking, particularly in countries with low underage drinking rates, such as Japan. Therefore, we aimed to investigate the relationship between exposure to advertising in various media and alcohol drinking among Japanese adolescents., Methods: We conducted a cross-sectional study involving 15,683 adolescents (51% girls) using data from a nationwide lifestyle survey in 2021 among junior and senior high schools across Japan. Media types were websites, stores, and public transportation. We defined current drinking as alcohol consumption of ≥1 day in the 30 days preceding the survey. Multivariable logistic regression was used to examine the association between exposure to alcohol advertisements and current drinking, adjusting for sex, grades, school area, lifestyle (bedtime and having fun at school), and addictive behaviors (smoking status and parents' alcohol consumption)., Results: The prevalence of current drinking was 2.2% (2.3% of boys and 2.0% of girls). Students who were exposed to any alcohol advertising media had higher odds of current drinking compared with those who were not (odds ratio, 1.48; 95% confidence interval [CI], 1.18-1.87). Students who were exposed to web, in-store, and public transportation advertisements had odds ratios of 1.44 (95% CI, 1.14-1.81), 1.62 (1.28-2.05), and 1.45 (1.06-1.98) of current drinking, respectively, compared with those who were not. The association of exposure to alcohol advertising media with the prevalence of current drinking was similar among boys and girls (all p for sex interaction >0.1), except for that of exposure to web advertisements; its association with current drinking was more pronounced in girls (p for sex interaction = 0.046). Exposure to a larger cumulative number of different alcohol advertising media was independently associated with a higher prevalence of current drinking among all students, boys, and girls (p-values for trend <0.001, 0.031, and <0.001, respectively; p for sex interaction = 0.085)., Conclusions: We found an association with a dose-response relationship between exposure to alcohol advertisements and current drinking among adolescents in junior and senior high schools across Japan. Our findings highlight the need for further advertising regulations to prevent underage drinking.

Background: While several studies have revealed that neurodevelopmental disorders have a high probability of overlapping with substance use disorders, the effects of neurodevelopmental disorders on the courses of substance use disorders have hardly been examined., Methods: This study targeted 637 alcohol-dependent individuals who received inpatient treatment and whose drinking situations were followed for 12 months after hospital discharge using mailed questionnaires. The comorbidity of psychiatric disorders and the characteristics associated with the neurodevelopmental disorders were assessed using several measurements at the time of hospital admission. The effects of neurodevelopmental disorders on the drinking courses of the subjects were then estimated., Results: The presence of a current depressive episode or any anxiety disorder significantly lowered the abstinence rates during the follow-up period (p = 0.0195 and p = 0.0214, respectively). ADHD traits as assessed using the ADHD Self-report Scale (ASRS) predicted a significantly poorer abstinence rate (p = 0.0296). Similarly, attention-deficit characteristics assessed objectively through interviews predicted a significantly lower abstinence rate (p = 0.0346), and a sensitivity analysis enhanced these results (p = 0.0019). When the drinking patterns were classified into three groups, the subjects with attention-deficit characteristics had a significantly higher rate of "Recurrence" and lower rates of "Abstinence" and "Controlled drinking" (p = 0.013). In a multivariate proportional hazards analysis, the ASRS score was significantly correlated with the re-drinking risk (p = 0.003)., Conclusion: ADHD traits had significant effects on not only abstinence rates, but also on drinking pattern. The presence of ADHD traits, especially attention-deficit characteristics, influenced the drinking courses of alcohol-dependent individuals after hospital treatment., (© 2022. The Author(s).)

Background: Excessive alcohol use is a leading cause of global morbidity and premature mortality. This study evaluated the effectiveness of two types of nurse-delivered interventions to reduce excessive alcohol consumption among screened participants using the alcohol use disorders identification test (AUDIT) in the workplace., Methods: A randomized controlled trial involving AUDIT-positive employees of five Japan-based companies was conducted. A total of 351 participants were randomized into groups that received a patient information leaflet (PIL), 5 min of brief advice, or 15 min of brief advice and counseling. Outcomes (weekly alcohol consumption and drinking and binge drinking frequency in the previous 30 days) were evaluated at 6 and 12-month follow-up., Results: The follow-up rates were 96.3% (n = 338) and 94.9% (n = 333) at 6 and 12 months, respectively. At 6 months, the mean change in weekly alcohol consumption was -38.1 g (-1.64 US fluid oz/week) in the 15-min brief advice and counseling group, which differed significantly from the PIL group. The reduction in the advice and counseling group persisted at 12-month follow-up but was no longer significantly different from the PIL group. There was no significant change in alcohol consumption observed in the 5-min brief advice group. Improvement in drinking and binge drinking frequency was observed in all three groups., Conclusions: Nurse-delivered 15-min brief advice and counseling was effective over a 6-month period in reducing alcohol consumption in a workplace setting. This finding suggests that the implementation of workplace screening and brief intervention could play a useful role in preventing the burden of harmful alcohol use., (© 2022 Research Society on Alcoholism.)

Background: While accumulating evidence suggests a relation between the severity of alcohol dependence and the risk of its recurrence, the impact of dependence severity on the course of the disorder has not been carefully evaluated. The present study examined the impact of several severity indices of alcohol dependence on the drinking course after inpatient treatment., Methods: This prospective study was conducted over a 12-month period following alcohol treatment at a specialized hospital. A total of 712 consecutively admitted alcohol-dependent patients were targeted for enrollment at the time of their hospitalization, with 637 patients registered and followed. The characteristics and severity of the subjects were assessed using multiple methods at admission, with their course after discharge followed continuously using mailed questionnaires that queried them regarding their drinking behavior., Results: Greater severity of dependence, assessed using the number of ICD-10 diagnostic criteria met, was associated with a lower rate of abstinence during the study period (p = 0.035). The rate of abstinence also decreased significantly as the baseline blood gamma-glutamyl transferase value and Alcohol Dependence Scale (ADS) score increased (p = 0.031 and p = 0.0002, respectively). In multivariate Cox proportional hazards analyses, the group with the most severe ADS scores had a significantly greater risk of relapse to drinking than the group with the least severe scores (HR = 2.67, p = 0.001). Dependence severity also associated with the drinking pattern; participants in both the controlled drinking group and the abstinence group had lower ADS scores at admission and a later age at first drinking (p = 0.001 and p < 0.001, respectively) than those with poorer drinking outcomes., Conclusions: The present study showed that more severe alcohol dependence predicts a poorer course after alcohol treatment, as reflected by findings on multiple measures. These results suggest that assessing the dependence severity at the outset of treatment could be useful both in predicting treatment outcome and targeting interventions to alcohol-dependent individuals who need additional support in their recovery., (© 2021 by the Research Society on Alcoholism.)

Background: Despite evidence regarding the effectiveness of screening and brief interventions for excessive alcohol use in primary care, these tools are not a part of routine practice. It has been suggested that using these tools at the workplace may be critical to alcohol-associated harm; however, evidence for this claim is unclear. The aim of this article is to develop a study protocol which evaluates the effect of brief alcohol intervention at the workplace to reduce harmful alcohol drinking., Methods: A randomized controlled trial involving employees (aged 20-74 years) of five Japan-based companies who were screened "positive" by Alcohol Use Disorder Identification Test (AUDIT) is on-going. Participants were randomized into "Patient Information Leaflet" (control group), "Brief Advice and Counselling," and "Five-minute Brief Advice" groups. A self-administered questionnaire was used to assess alcohol consumption, lifestyle behavior, health status, work performance, and consequences of alcohol use. Data of laboratory markers were collected from routine health checkups., Results: A total of 351 participants were randomized into Patient Information Leaflet ( n = 111), Brief Advice and Counselling ( n = 128), and Five-minute Brief Advice ( n = 112) groups. Participants were mostly men with a median age of 49 years. Median AUDIT score and weekly alcohol consumption were 11 points and 238 g/week, respectively. Two-thirds of the participants were manufacturing workers., Conclusion: This study protocol developed the first trial in Japan to investigate the effect of brief alcohol intervention combined with a recommended screening tool at the workplace. Our findings can provide evidence on the effectiveness and relevance of these tools to occupational health., Competing Interests: The authors declare no conflict of interest., (©2021 Tottori University Medical Press.)

Objectives: This study aimed to assess trends in the prevalence of alcohol use depending on smoking behaviours and that of smoking depending on drinking behaviours among Japanese adolescents., Design: This was a retrospective study using Japanese school-based nationwide surveys conducted between 1996 and 2017., Setting: Surveyed schools, both junior and senior high schools, considered representative of the entire Japanese population, were sampled randomly., Participants: We enrolled 11 584-64 152 students from 179 to 103 schools yearly. They completed a self-reported and anonymous questionnaire on smoking and drinking behaviour., Results: Since 1996, the prevalence of alcohol use and smoking among adolescents decreased in each survey (p<0.01). The prevalence of alcohol use in the non-smokers group was 29.0% in 1996 and 4.0% in 2017, and in the smokers group, it was 73.3% in 1996 and 57.4% in 2017. The reduction rate (the difference in prevalence between 1996 and 2017 divided by the prevalence in 1996) was 0.86 in the non-smokers group and 0.22 in the smokers group. The prevalence of smoking in the non-drinkers group was 6.7% in 1996 and 0.7% in 2017, while that in the drinkers group was 32.5% in 1996 and 18.9% in 2017. The reduction rate was 0.90 in the non-drinkers group and 0.42 in the drinkers group. Therefore, downward trends differed among the groups. In a subanalysis of senior high school students, we divided students into three groups according to their intention to pursue further education. Between 1996 and 2017, there was a consistent difference in the prevalence of alcohol use and smoking among these groups., Conclusions: Alcohol use and smoking among Japanese adolescents seem to have reduced. However, certain groups showed poor improvements, and health risk behaviour disparity exists, which may widen further. We need to focus on high-risk groups and implement appropriate measures or interventions accordingly., 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.)

Background: Inactive aldehyde dehydrogenase-2 (ALDH2) is a well-known deterrent to the development of alcohol use disorder (AUD), and however, some individuals with inactive ALDH2 do go on to develop AUD. These alcoholics are likely to have strong risk factors for the development of this disorder. Using a model of alcoholics with inactive ALDH2 (the AIA model), we investigated the unique characteristics of alcoholics with inactive ALDH2 in an attempt to identify the risk factors for AUD. In this study, we focused on comorbid psychiatric and personality disorders as potential risk factors for AUD., Methods: The subjects were 103 male alcoholics with inactive ALDH2 (AIAs), 87 age- and ADH1B genotype-matched alcoholics with active ALDH2 (AAAs) and 200 age-matched healthy men. The alcoholics were divided into 4 subgroups according to their ALDH2 and ADH1B genotypes (inactive ALDH2 vs. active ALDH2, usual ADH1B vs. superactive ADH1B). To assess the participants' comorbid psychiatric disorders, we conducted semi-structured interviews using the Japanese translation of SSAGA version 2. We compared the prevalence of comorbid psychiatric and personality disorders among groups with different combinations of the ALDH2 and ADH1B genotypes., Results: The prevalence of attention-deficit/hyperactivity disorder (ADHD) was significantly higher in the AIAs with usual ADH1B than in the other 3 subgroups of alcoholics. In contrast, the prevalence rates of agoraphobia and panic disorder were significantly lower in the AIAs with superactive ADH1B than in the other 3 subgroups of alcoholics., Conclusions: This study suggested that (i) ADHD is a risk factor for AUD, consistent with previous reports; (ii) agoraphobia and panic disorder may have deterrent effects against the development of AUD in individuals with inactive ALDH2, probably attributable to the similarity between the symptoms of agoraphobia and panic disorder and the adverse reactions to consumption of alcohol in subjects with inactive ALDH2., (© 2020 by the Research Society on Alcoholism.)

Background: In areas affected by the tsunami of the great East Japan Earthquake, smoking behavior may have deteriorated due to high stress and drastic changes in living environment. Surveys were conducted to reveal changes in smoking behaviors among victims., Methods: A population-based random-sample home-visit interview survey of victims in Iwate and Miyagi Prefectures affected by the tsunami disaster was conducted in 2012 (n = 1978), while a population-based nationwide survey was conducted in 2013 (n = 1082). A panel survey in 2014 was conducted with respondents of the 2012 survey (n = 930). Multiple logistic regression analysis was performed to reveal factors related to smoking status after the disaster., Results: There was high smoking prevalence of both sexes in the tsunami disaster area (current smoking rate in coastal area, 50.0% for male, 21.4% for female; inland area, 34.7% for male, 7.6% for female). Low prevalence of male quitters was observed (quitter rate in coastal area, 20.8% for male, 8.0% for female; inland area, 23.4% for male, 5.5% for female). The prevalence of nicotine-dependent people assessed by FTND (Fagerström Test for Nicotine Dependence) in the coastal area was also higher than in the inland area or other areas of Japan. Smoking behavior among victims worsened after the disaster and did not improve 3 years from the disaster. Post-disaster factors related to smoking were living in coastal area, complete destruction of house, and living in temporary housing., Conclusions: Smoking prevalence and the level of nicotine dependence of tsunami victims were still high even 3 years after the disaster. It is important to emphasize measures for smoking control in the disaster areas for an extended time period.

Background: The presence of large or multiple esophageal distinct iodine-unstained lesions (DIULs) is a strong predictor of field cancerization in the upper aerodigestive tract. Several risk factors for DIULs, including genetic polymorphisms of alcohol and aldehyde dehydrogenases (ADH1B, rs1229984; ALDH2, rs671), have been demonstrated in Japanese alcohol-dependent men. However, few evaluations of alcohol-dependent women have been conducted in this field., Methods: Using multiple logistic regression models, we investigated the results of screening using esophageal iodine staining and the identification of determinants for esophageal DIULs in 472 Japanese alcohol-dependent women., Results: DIULs ≥5 mm, multiple DILUs, and both characteristics were observed in 35 (7.4%), 31 (6.6%), and 16 (3.4%) patients, respectively. DIULs ≥5 mm were histologically diagnosed as low-grade intraepithelial neoplasia in 26 patients and superficial squamous cell carcinoma in 9 patients. Although the inactive heterozygous ALDH2*1/*2 genotype was more common (33.3% vs. 11.4%, p = 0.002) in the group with DIULs ≥5 mm than in the group without DIULs ≥5 mm, no significant differences in the results of a questionnaire asking about current and past facial flushing after a glass of beer were seen between the groups with and without DIULs ≥5 mm. When individuals with current or former flushing were assumed to have inactive ALDH2, the sensitivity and specificity of current or former flushing to identify the presence of inactive ALDH2 were 50.0% and 93.5%, respectively; these values were previously reported to be 88% and 92%, respectively, in a Japanese general female population. The low sensitivity in the present study suggests that a lack of alcohol flushing may play a crucial role in the development of alcohol dependence in women with inactive ALDH2. No significant differences in age, usual alcohol consumption, or smoking habits were observed according to ADH1B and ALDH2 genotypes. Multiple logistic regression analyses showed that the slow-metabolizing ADH1B*1/*1 genotype (odds ratio [95% confidence interval], 12.5 [4.82-32.4] and 9.89 [3.50-27.9]), the inactive heterozygous ALDH2*1/*2 genotype (2.94 [1.18-7.38] and 3.79 [1.40-10.3]), a lower body mass index per -1 kg/m2 (1.17 [1.02-1.35] and 1.38 [1.14-1.67]), and a mean corpuscular volume ≥106 fl (3.70 [1.56-8.81] and 3.27 [1.24-8.64]) increased the risk of DIULs ≥5 mm and multiple DIULs, respectively. The combination of ADH1B*1/*1 and ALDH2*1/*2 markedly increased the risk of esophageal DIULs ≥5 mm (39.3 [10.6-146])., Conclusions: Japanese alcohol-dependent women shared several common risk factors for esophageal squamous cell neoplasia with alcohol-dependent men, but with considerably different magnitudes., Competing Interests: The authors have declared that no competing interests exist.

Coping skills training (CST) and cue exposure treatment (CET) have yielded favorable outcomes when used to treat alcoholics. We conducted 6-week inpatient programs that consisted of 9 CST group sessions (n = 117) during 2005-2009 and 9 CST group sessions plus 4 CET group sessions (n = 49) during 2009-2011 and subsequent 1-year letter therapy for Japanese alcoholic men who had relapsed and been readmitted after standard cognitive-behavioral inpatient therapy. When patients received a letter containing encouraging words every 2 weeks, they were asked to reread their CST and CET records and to respond to the letter by marking drinking days on a calendar and naming the skills on a list of the 9 CST themes and CET that were useful for maintaining abstinence during that 2-week period. The estimated percentages of achievement of 30 or fewer drinking days during the one year of letter therapy were 36.1 - 45.8%. 'Non-smoking', '2nd admission', and 'After age-limit job retirement' were significant factors in achieving good outcomes. The 'usefulness' responses for 'Increasing pleasant activities', 'CET', 'Anger management', ' Managing negative thinking', 'Problem solving', and ' Seemingly irrelevant decisions' as percentages of overall responses to the letters were significantly higher, in order of decreasing percentages, in the achiever group than in the non-achiever group, but the differences between the groups in ' Managing urges to drink', ' Drink refusal skills', ' Planning for emergencies', and ' Receiving criticism about drinking' were not significant. The odds ratios for achievement of 30 or fewer drinking days during the 1-year period increased significantly by 1.15 -1.31 fold per 10% increment in the 'usefulness' ratio for 'Increasing pleasant activities'. The difference in percentage achievement between the group treated by CST alone and the group treated by CST plus CET was not significant. In conclusion, some coping skills were more useful for relapse prevention than others in this study population, and addition of CET to CST and subsequent letter therapy did not improve outcomes.

Alcoholics have a high prevalence of nicotine dependence, and smoking is a major contributor to their high mortality. Three weeks after admission to an addiction center in Japan, 193 alcoholic men who were participating in an 11-week concurrent inpatient smoking cessation and alcohol abstinence programs filled out an anonymous self-report questionnaire regarding smoking and drinking, and 6 months after the completion of the programs, 83 patients were asked to respond to a mailed questionnaire about their smoking and drinking status. Of the 193 subjects, 73.3% were current smokers, but many were highly motivated in regard to both smoking cessation and alcohol abstinence. The subjects' scores on a 0 to 10 point scale for rating motivation and confidence in regard to smoking cessation and smoking urge were significantly correlated with each other and with their scores for motivation and confidence in regard to alcohol abstinence and drinking urge. Three weeks after admission, varenicline treatment was well-tolerated, and the varenicline group had a high rate of smoking cessation than the smoker group not treated with varenicline (67.7% vs. 44.6%, p = 0.012). Forty-six (55.4%) of the 83 subjects who were mailed the questionnaire responded, and the drinking category was 'totally abstinent' in 35 subjects (42.2%), and 'mostly abstinent' in another 4 subjects (4.8%). Seventeen (20.5%) of the 83 subjects were non-smokers before treatment, but after treatment, 23 (50.0%) of the 46 responders and 20 (51.3%) of the 'totally or mostly abstinent' 39 responders were total or almost non-smokers. The response rate of 'totally or mostly abstinent' was higher among the 17 non-smokers before treatment than among the 66 smokers before treatment (70.6% vs. 40.9%, p = 0.033), and the age-adjusted odds ratio (95% confidence interval) for the response of 'totally or mostly abstinent' was 3.30 (1.03-10.56) for the non-smokers before treatment (vs. the smokers before treatment). In conclusion, smoking status had a great impact on the drinking status of treatment-seeking alcoholic men, and smoking cessation should be recommended to smoking alcoholics.

Aims: This study evaluated the acceptance of controlled drinking (CD) goals among physicians specializing in the treatment of alcohol dependence (AD) in Japan., Methods: A mailed questionnaire survey was sent to physician members of the Japanese Society of Alcohol-Related Problems (n = 232) who were specialists in the treatment of AD in Japan. The evaluated items included the acceptance of CD goals, the definition of CD, the reasons for accepting or rejecting CD and the patient factors used to make treatment-goal decisions., Results: CD as an interim goal on the way toward abstinence was accepted by about two-thirds of the specialists, while CD as a final goal was accepted by about one-third of specialists. Specialists supported harm-free drinking and a satisfactory quality of life, rather than alcohol consumption limits, as the definition of CD. Of note, a significantly higher percentage of specialists who rejected CD, compared with those who accepted CD, supported the disease model of AD as grounds for their decision. Specialists who accepted CD relied mostly on factors such as the severity of dependence, attitude toward CD and abstinence, and the level of psychological dependence and social stability, when making treatment-goal decisions., Conclusion: CD was accepted as an interim goal by two-thirds and as a final goal by one-third of Japanese physician specialists. Despite differences in drinking cultures and treatment circumstances, great similarities were found between this study and those conducted in Europe and North America with regard to the reasoning of treatment providers and the use of patient characteristics to make treatment-goal decisions., (© The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

We conducted a survey of alcohol-dependent patients at the time of their first visit and physicians in regard to the goals of treatment of alcohol dependence. There were 99 replies from patients, and replies from physicians related to 64 of the patients' replies were also received, and in 25.0% of them it was judged possible to make reducing the amount of alcohol consumed a temporary or final goal. Having a mild drinking problem, the absence of a personality disorder or mental retardation, the presence of a strong motivation in regard to treatment, etc., were cited as reasons for the physicians' judgments. In addition, the number of diagnostic criteria of the ICD-10 for dependence syndrome that applied was shown to be significantly related to the judgments regarding treatment goals. However, as for Alcohol Dependence Scale (ADS), there was no significant relationship with the treatment goal.

Since the 1990s, we have suggested the concept of pre-alcoholism which encompasses patients who have drunk a great deal of alcohol leading to alcohol related problems such as health issues, domestic violence, drunken driving and black-outs. Pre-alcoholism excludes alcohol-dependent patients who have experienced continuous drinking or withdrawal symptoms. We have treated many outpatients with pre-alcoholism for several years. Our regimen demands that the patients must be abstinent for half a year at the beginning of their treatment. After half a year they can choose whether they will continue to be abstinent or they will resume drinking with the aim of reducing their total alcohol consumption. The study clarified the character of pre-alcoholism by investigation of the patients' background and re-diagnosis of the patients based on the International Classification of Diseases, 10th Revision (ICD-10). A remarkable ratio of pre-alcoholic patients was diagnosed with alcohol dependence under ICD-10. We classified pre-alcoholic patients into two groups, one diagnosed as having ICD-10-classed alcohol dependence and the other which did not fulfill the ICD-10 diagnostic criteria of alcohol dependence, and examined the therapeutic processes of the two groups. It was shown that most pre-alcoholic patients could finally take required courses of treatment by themselves without regard to diagnosis under ICD-10, even if they chose any treatment and made alcohol related mistakes on the way. Our findings suggested that pre-alcoholic patients, a portion of whom may have exhibited mild alcohol dependence, could select drinking reduction as a primary goal of treatment after a certain period of abstinence.

Background: Human twin studies have shown that certain responses to alcohol, including subjective perceptions, are genetically influenced. Previous studies have provided evidence that a low level of response to alcohol predicts future alcohol use disorders in humans. Recent genetic studies suggest an association between alcohol dependence and genetic variation in the γ-aminobutyric acid A (GABA(A)) receptor α2 subunit gene (GABRA2). Based on a haplotypic association of alcohol dependence with GABRA2, we investigated whether GABRA2 alleles are associated with the subjective responses to clamped alcohol concentration., Methods: One hundred and ten healthy social drinkers (53 men) underwent the alcohol clamp. Fifteen minutes after the start of an intravenous infusion of alcohol, the breath alcohol concentration was clamped at a target of 50 ± 5 mg/dl for 165 minutes. Subjective physiologic responses to alcohol and stimulant and sedative effects of alcohol were measured repeatedly during the alcohol clamp. Because aldehyde dehydrogenase 2 (ALDH2) has been shown to have a great impact on the subjective responses to alcohol, we divided subjects by ALDH2 genotype for further analyses. To examine the role of genetic variation in GABRA2, 7 single nucleotide polymorphisms (SNPs) that were informative in association studies were included as factors in the analysis., Results: Among these 7 SNPs, 3 SNPs (rs279869, rs279858, and rs279837) located in the middle of the GABRA2 gene showed significant associations with subjective effects of alcohol. Subjects with 1 or 2 copies of the more common allele showed greater subjective responses to alcohol than did individuals homozygous for the alcohol dependence-associated allele regardless of ALDH2 genotype., Conclusions: These findings confirm and extend the observation that the GABRA2 alleles affect the subjective responses to alcohol, and suggest that the genetic variations in GABRA2 might play a role in the risk of alcohol use disorders by moderating the subjective effects of alcohol., (Copyright © 2010 by the Research Society on Alcoholism.)

Malnutrition and emaciation in alcoholics is associated with various alcoholism-related diseases, including Wernicke's encephalopathy, aero-digestive tract cancer, and serious metabolic disorders. We used a self-administered questionnaire survey for structured dietary habit screening to evaluate the dietary profiles of 467 Japanese alcoholic men aged 40 years or over and their relationship to body mass index (BMI). Their average daily ethanol consumption was 119 +/- 65 g (845 +/- 463 kcal). The survey showed that 50.5% of the subjects consumed three meals a day; 32.8%, two meals; 12.2%, one meal; and 4.5% rarely ate. The meals mainly consisted of carbohydrates and protein, with few vegetables. Daily alcohol consumption was inversely correlated with the frequency of meals, drinking milk, and consuming confectionery. The subjects who lived with their family (72.8%) consumed more meals than the subjects liv- ing alone. After excluding 22 subjects with leg edema or ascites, the average BMI was 21.3 +/- 3.2. The group with the lowest BMI values (<18.5) accounted for 19.3% of the subjects, and those with the highest BMI values (> or = 25) accounted for 11.5%. A multivariate stepwise logistic analysis showed that BMI increased 0.15 per 22 g ethanol consumed daily and decreased 0.03 per + 10 cigarettes smoked daily, 0.43 per decrease by one in daily frequency of meals, and 0.54 per category (daily, occasionally, rarely, seldom) of milk consumption. The likelihood of a low BMI <18.5 was significantly and independently associated with smoking [OR (95%CI) =1.24 (1.02-1.51) per +10 cigarettes] and with intake of seafood [0.62 (0.41-0.94) per +1 category], milk [1.52 (1.16-2.00) per +1 category] and green and yellow vegetables [1.52 (1.05-2.21) per +1 category]. Intervention in regard to diet as well as drinking is important to preventing malnutrition and emaciation in alcoholics.

Objective: Limited neuronal cell loss is seen in the neuropathology of Wernicke's encephalopathy (WE), but the extent of neuronal damage has not been well studied. Moreover, there is still a debate as to whether alcohol itself causes brain damage in humans. Although, it is difficult to examine the extent of neuronal damage in living patients, recent studies have revealed that total tau protein levels in the cerebrospinal fluid (CSF) reflect the rate of neuronal degeneration. Therefore, we hypothesized that the elevated CSF total tau in patients with WE was due to neuronal damage and thus we examined CSF total tau protein in patients with WE, as well as in those with alcohol withdrawal delirium (WD) and Korsakoff syndrome (KS). We also examined CSF total tau in nonalcohol dependent patients with Alzheimer's disease (AD) as a disease control., Methods: CSF samples were obtained from 13 acute WE patients with alcohol dependence, 9 WD patients with alcohol dependence and 16 KS patients with alcohol dependence, and from 20 nonalcohol dependent AD patients. CSF was also obtained from 10 of the WE patients after their disease had progressed to the chronic stage. CSF tau protein levels in all samples were determined by sandwich enzyme-linked immunosorbent assay. Tau phosphorylated at threonine 181 (p-tau(181)) and amyloid beta-protein ending at amino acid 42 (A beta 42) in CSF were also determined for comparison between acute WE with AD., Results: Total tau was significantly elevated in acute WE and decreased on long-term follow-up, but was not elevated in WD or KS. The patterns of p-tau(181) and A beta 42 differed between acute WE and AD., Conclusions: Intense neuronal cell death occurs transiently in WE, and the mechanism differs from that in AD. Neuronal damage is generally unaccompanied in WD. These results suggest that CSF total tau is a useful biological marker for WE.

Aims: The purpose of this paper is to outline alcohol availability, alcohol consumption and related harm, alcohol control policy and prevention programmes in Japan, few of which have been discussed in either the Japanese or English literature., Methods: Data were collected primarily from the following two sources: statistics and survey results issued by the national government, including surveys funded by the government; and papers published since 2000, identified by searching the MEDLINE and Igaku-Chuo-Zasshi databases. These data were assessed regarding their quality and summarized. Some data presented here were produced specifically for this review., Results: Although per capita alcohol consumption has tended to decline for more than 10 years, it has remained at a high level. Diversification of the drinking population has progressed rapidly, specifically in women, among whom alcohol consumption has increased sharply. Cross-sectional data suggest that alcohol consumption is associated with serious health and social consequences. Existing longitudinal data suggest that alcohol-related problems, especially health problems, have increased steadily over the past several decades, with few exceptions, including alcohol-related fatal road traffic accidents. Alcohol policy and prevention programmes have not developed to a level that can control these problems adequately. Specifically, the high availability of alcoholic beverages, including the lack of restrictions on sales and advertising and decreasing prices, are noted., Conclusions: This review provides basic information regarding alcohol availability and alcohol consumption and related harm that may facilitate the improvement of existing alcohol control measures in Japan and encourage the development of new alcohol control measures. This research revealed the scarcity of longitudinal data regarding alcohol consumption and its consequences, and the lack of several important variables, such as disability adjusted life years, for improving our understanding of the comprehensive status of alcohol in Japan.

Objectives: Alcohol dependence has been associated with disrupted neuroendocrine systems, impulsivity in intertemporal choice (delay discounting). However, little is known regarding stability of discount rates in alcoholics. This study examined both differential stability (stability of individual differences) and absolute stability (stability of group mean) of hyperbolic discount rates for monetary gains in severe alcoholic inpatients (diagnosed with DSM-IV) over a 2-month period during abstinence., Methods: We estimated male alcoholics' discount rates for delayed monetary rewards on the basis of their pattern of choices between smaller immediate rewards (1,100-8,000 yen) and larger, delayed rewards (2,500-8,500 yen; at delays from 1 week to 6 months), two times at 2-month time-interval during hospitalized alcohol withdrawal., Results: It was observed that the alcoholics' mean hyperbolic discount rates for gains had both differential and absolute stability over 2 months, although a slight non-significant decrease in the group mean of the discount rates was observed., Conclusions: The results indicate that abstinent alcoholic's discount rates are stable over a relatively long-term period. The usefulness of assessing discount rates of addicts in psychoneuroendocrinology and neuroeconomics of addiction is discussed.

The treatment costs of alcohol dependence were calculated by disease stage and by method of treatment. Alcohol-related problems, mainly alcohol dependence, can be divided into four stages for convenience: (1) abnormal values found in health examinations, (2) preventive treatment as an outpatient or short-term hospitalization for education and testing, (3) basic outpatient treatment, and (4) inpatient treatment. The following results were obtained. (1) One example of expenses required for a routine examination was 936 points when converted to health insurance points. (2) The number of points for outpatient group psychotherapy in the first education stage and five additional examinations was 5175 points (6255 points with a designated mental health physician). The number of points for the program of medical tests and initial education in one week of hospitalization was 10,787. (3) For alcoholics, continued outpatient visits for two years, the number of points for only prescription of a drug to inhibit drinking such as disulfiram with no testing was 14,790 (19,650 points with a designated mental health physician). When the patient participated in alcohol daycare, the total number of points for three months of daycare with one meal each time was 46,020. (4) In cases of three-month inpatient treatment in our hospital including ordinary medical testing, the number of points for the first month for one patient was 57,280 points, plus 35,000 points each month in the 2nd and 3rd months for a total of 127,280 points. However, the total in our hospital is an average of 160,200 points when drugs and additional tests are included. As expected, the expenses required at the primary prevention stage were low, while those required for treatment after onset were high. Placing stress on prevention, providing proper treatment for patients and reducing relapses will reduce the burden including social expenses.