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The predominant approach of public health experts to cigarette smoking might be described as behaviorist, for it aims to eliminate this behavior without attending to human agency and intention. The requirement that physicians address smoking cessation at every patient visit also constitutes physicians as "managers" who focus narrowly on technical means to achieve predetermined ends. In this paper, I contrast such an approach with the Aristotelian tradition, according to which physician and patient ought to develop the virtue of temperance that would allow the patient to quit smoking. Although this model could potentially mitigate medicine's behaviorist-managerial tendencies, I follow Aristotle to argue that it requires a moral friendship in which participants share a conception of the human good and pursue that good together. Due to the intractable moral pluralism that characterizes contemporary life, physicians and patients are unlikely to achieve this sort of friendship, making Aristotelian medicine impracticable at present., (© The Author(s) 2019. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study presents an updated meta-analysis replicating the study of (Stavro, K., Pelletier, J., & Potvin, S. (2013). Widespread and sustained cognitive deficits in alcoholism: A meta-analysis. Addiction Biology, 18, 203-213. doi:10.1111/j.1369-1600.2011.00418.x) regarding the cognitive functioning of alcoholics as a function of time abstinent., Methods: A total of 34 studies (including a total of 2,786 participants) that met pre-determined inclusion and exclusion criteria were included in the analyses. The alcoholics were categorised into recently detoxified alcoholics (0-31 days sober), alcoholics 32-365 days sober and alcoholics >365 days sober consistent with the previous study. The current study employed more stringent control on the tests included in the analysis to include only those tasks described in contemporary neuropsychological test compendia. Forty-seven percent of the papers surveyed were not include in the previous meta-analysis., Results: The results indicated that there was a diffuse and pervasive pattern of cognitive deficit among recently detoxified alcoholics and that these deficits, particularly with regard to memory functioning, persisted even in longer term abstinent alcoholics. This was inconsistent with the prior meta-analysis which contended that significant cognitive recovery was possible after as little as 1 year., Conclusion: The persisting cognitive deficits were noted across a wide range of cognitive functions, supporting the notion of a diffuse rather than a specific compromise of cognition in alcoholism following discontinuation, as measured using standardised neuropsychological tests. Limitations on the finding included the fact that it was a cross-sectional rather than a longitudinal analysis, was subject to heterogeneity of method, had low representation of females in the samples, and had fewer studies of long-term sober samples., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To assess whether health changes affect cessation of alcohol consumption and to compare the health status of former drinkers and abstainers., Methods: Cohort data from 9001 Korean participants aged 40-69 years old were analyzed. Alcohol consumption was assessed every 2 years for 10 years. Participant age, sex, marital status, education level, employment status, smoking, chronic disease, perceived health and changes in these variables were analyzed to identify factors associated with quitting alcohol drinking. The number of diseases and perceived health of former drinkers and people who at baseline were lifetime abstainers were compared., Results: Among 4037 drinkers at baseline, 673 (16.7%) were classed as quitters and 3364 (83.3%) were classed as non-quitters. Sex, age and worsened perception of health were significantly associated with cessation of drinking. Women and individuals >60 years were more likely to cease drinking. There was a significant association between disease onset or treatment and alcohol cessation for cancer cases, but not for cardiovascular disease or chronic disease cases. There was no significant difference in number of diseases or perceived health between former drinkers and people who at baseline were lifetime abstainers., Conclusions: The effect of disease onset or treatment on alcohol consumption cessation depended on disease type. Former drinkers did not show significantly worse health than people who at baseline were lifetime abstainers. Further studies of alcohol consumption and its effects on health are needed to consider disease occurrence and changes in alcohol consumption., Short Summary: Disease onset or treatment significantly affected alcohol consumption cessation for cancer cases, but not for cardiovascular disease or other chronic disease cases. There was no significant difference in health status between former drinkers and lifetime abstainers., (© The Author 2016. Medical Council on Alcohol and Oxford University Press.)

Aims: To compare levels of phosphatidylethanol (PEth) to self-reported alcohol intake among young adult binge drinkers (18-30 years)., Methods: Abstainers (n = 23), moderate (n = 22), and binge drinkers (n = 58) completed an alcohol consumption questionnaire and the AUDIT. PEth was measured in whole blood and dried blood spots via high-performance liquid chromatography with tandem mass spectrometry. Also measured was mean corpuscular volume (MCV) and gamma glutamyl transpeptidase (GGT)., Results: Most subjects were female (65%) and Caucasian (73%). Among binge drinkers, past-month average number of binge episodes was 7.2 ± 4; average duration of binge drinking behavior was 4.3 ± 3 years. AUDIT scores and PEth levels (ng/ml) in whole blood or dried blood spots were significantly (P < 0.001) greater in binge drinkers (13 ± 4, 186 ± 170, and 65 ± 53, respectively) compared to moderate drinkers (6 ± 3, 24 ± 29, and 11 ± 13, respectively) and abstainers (0.6 ± 0.89, 0, and 0, respectively). No differences were found in MCV and GGT among groups. There were significant correlations between whole blood and dried blood spot PEth levels and AUDIT scores (Spearman's r = 0.745 and 0.738, P < 0.0001, respectively), and whole blood and dried blood spot PEth levels were significantly correlated (0.899, P < 0.0001)., Conclusions: PEth levels measured in whole blood and dried blood spots were significantly greater in binge drinkers compared to abstainers and moderate drinkers, and these levels were positively correlated with AUDIT scores., (© The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Historians have recognized that men with drinking problems were not simply the passive subjects of medical reform and urban social control in Gilded Age and Progressive Era America but also actively shaped the partial medicalization of habitual drunkenness. The role played by evangelical religion in constituting their agency and in the historical process of medicalization has not been adequately explored, however. A post-Civil War evangelical reform culture supported institutions that treated inebriates along voluntary, religious lines and lionized former drunkards who publicly promoted a spiritual cure for habitual drunkenness. This article documents the historical development and characteristic practices of this reform culture, the voluntarist treatment institutions associated with it, and the hostile reaction that developed among medical reformers who sought to treat intemperance as a disease called inebriety. Those physicians' attempts to promote therapeutic coercion for inebriates as medical orthodoxy and to deprive voluntarist institutions of public recognition failed, as did their efforts to characterize reformed drunkards who endorsed voluntary cures as suffering from delusions arising from their disease. Instead, evangelical traditions continued to empower reformed drunkards to publicize their own views on their malady which laid the groundwork for continued public interest in alcoholics' personal narratives in the twentieth century. Meanwhile, institutions that accommodated inebriates' voluntarist preferences proliferated after 1890, marginalizing the medical inebriety movement and its coercive therapeutics., (© The Author 2013. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: The assessment of relapses is widely used as an outcome measure of alcohol dependence treatment. However, the methods of assessing relapses range from questionnaires to biological markers of alcohol for different time spans. The aim of this study was to compare the relapse rates of weekend home stays during long-term alcohol dependence treatment, assessed by ethyl glucuronide (EtG), breath alcohol tests and self-reports., Methods: Two hundred and ninety-seven alcohol-dependent patients receiving a long-term inpatient treatment programme participated. After a weekend at home (Friday to Sunday) they were evaluated for relapse by personal interviews and with breath alcohol tests. A concomitantly collected urine sample was later assessed for EtG with liquid chromatography-tandem mass spectrometry (LC-MS/MS analysis)., Results: Of the total, 37.7% of the patients were positive for EtG at least once. Breath alcohol tests had been positive in only 4.4% and in personal interviews only 5.7% of the patients had admitted relapse. 15.6% of EtG tests were positive, but breath alcohol tests were negative (Cohen's kappa = 0.056). Ninety-three per cent of the relapses were only detected by EtG., Conclusion: In addition to breath alcohol tests and interviews, urinary EtG can clearly improve the verification of relapse in inpatient treatment programmes allowing for weekend stays at home. Without EtG testing, a high amount of relapses will stay undetected.

Aims: The aim of the study was to explore neurometabolic and associated cognitive characteristics of patients with polysubstance use (PSU) in comparison with patients with predominant alcohol use using proton magnetic resonance spectroscopy., Methods: Brain metabolite concentrations were examined in lobar and subcortical brain regions of three age-matched groups: 1-month-abstinent alcohol-dependent PSU, 1-month-abstinent individuals dependent on alcohol alone (ALC) and light drinking controls (CON). Neuropsychological testing assessed cognitive function., Results: While CON and ALC had similar metabolite levels, persistent metabolic abnormalities (primarily higher myo-inositol) were present in temporal gray matter, cerebellar vermis and lenticular nuclei of PSU. Moreover, lower cortical gray matter concentration of the neuronal marker N-acetylaspartate within PSU correlated with higher cocaine (but not alcohol) use quantities and with a reduced cognitive processing speed., Conclusions: These metabolite group differences reflect cellular/astroglial injury and/or dysfunction in alcohol-dependent PSU. Associations of other metabolite concentrations with neurocognitive performance suggest their functional relevance. The metabolic alterations in PSU may represent polydrug abuse biomarkers and/or potential targets for pharmacological and behavioral PSU-specific treatment.

Aim: Optimal management of hepatitis C virus (HCV) infection is controversial in heavy drinkers. We compared the management of HCV infection of heavy drinkers with that of patients without a history of alcohol abuse., Methods: In a retrospective case-control study, 69 HCV-infected heavy drinkers [daily alcohol consumption at referral above 60 g/day, hereafter 'alcohol group'] were compared with matched HCV-infected patients with low alcohol consumption (<40 g/day, 'control group')., Results: Patients of the 'alcohol group' were younger (42 vs. 45 years, P = 0.05), more often male (69.6 vs. 56.5%, P = 0.11) and had been infected by intravenous drug use (85.5 vs. 45.0%, P < 0.0001). The percentage of patients with a recommendation for treatment according to the French 2002 consensus (bridging fibrosis or genotype 2 or 3) was 52 of 69 (75.4%) in both groups, while the proportion of patients treated was higher in the control group (71.0 vs. 44.9%, P = 0.002). In the 'alcohol group', patients had better access to treatment if they were employed or consumed 170 g/day or less at first referral. Sustained virological response (SVR) was obtained in 10 of 31 patients (32.3%) of the 'alcohol group' vs. 8 of 31 patients (25.8%) of the control group matched for genotype and type of treatment (P = 0.58)., Conclusion: Heavy drinkers are less often considered for antiviral therapy compared with patients without a history of alcohol abuse. However, once treatment is actually initiated, SVR rates are comparable with those achieved in non-drinkers despite the continuation of alcohol consumption during therapy in some patients.

Aims: Carbohydrate-deficient transferrin (%CDT) is a well-established and highly specific biomarker for sustained heavy consumption of alcohol. However, in pregnant women, the specificity of this biomarker might be affected by advanced gestational age, even after accounting for increased transferrin concentrations in pregnancy. The goal of this prospective study was to assess the variability in %CDT during pregnancy among alcohol-abstaining patients., Methods: Patients were recruited during one of the first prenatal care visits and followed-up to term. Abstinence was confirmed by maternal self-report and by alcohol biomarkers. Biomarkers assessed in the mother included serum gamma-glutamyltranspeptidase, urine ethyl glucuronide and ethyl sulfate, and whole blood phosphatidylethanol (PEth). In addition, PEth was measured in a dry blood spot card obtained from a newborn. For %CDT analysis, serum samples were collected at baseline and at term and analyzed by an internationally validated high-performance liquid chromatography and spectrophotometric detection method., Results: At recruitment (mean gestational age 22.6 ± 7.3 weeks), the mean %CDT concentration was 1.49 ± 0.30%, while at term, it increased to 1.67 ± 0.28% (P = 0.001). Using a conventional cutoff concentration %CDT >1.7%, 22.9 and 45.7% of the sample would be classified as 'positive' for this biomarker at recruitment and at term, respectively (P = 0.011 )., Conclusion: These results suggest that a conventional cutoff of 1.7% might be too low for pregnant women and would generate false-positive results. We propose that %CDT >2.0% be used as a cutoff concentration indicative of alcohol exposure in pregnant women. The sensitivity of %CDT at this cutoff for heavy drinking during pregnancy needs to be assessed further.

Aims: The TaqIA polymorphism of the dopamine D2 receptor (DRD2) gene has been extensively studied in relation to alcoholism, and the TaqI A1 allele appears to be over-represented in alcohol-dependent individuals. In a recent study, this allele has also been associated with a highly increased mortality rate in alcohol-dependent individuals. In the present study, we investigated whether the TaqI A1 allele of the DRD2 gene region was associated with a higher relapse rate in alcohol-dependent individuals., Methods: Adult women (n = 10) and men (n = 40) with a diagnosis of alcohol-dependence were recruited from two Swedish 12-step treatment units for alcoholism. Subjects were genotyped for the TaqIA polymorphism. On average, 1&frac12; year after the end of the treatment program, subjects were re-interviewed by using the alcohol-related items from the Addiction Severity Index follow-up version., Results: Thirty-three (66%) subjects self-reported relapse and 17 (34%) abstinence during the follow-up period. Thirty-sex percent (18/50) were carriers of the A1 allele of the DRD2 gene region, and 64% (32/50) were non-carriers. Among the carriers of the A1 allele, 89% (16/18) reported relapse in contrast to 53% (17/32) in the non-carriers (P = 0.01; odds ratio = 7.1)., Conclusion: The present study is, to our knowledge, the first report of an association between the TaqI A1 allele and a substantially increased relapse rate. It should be emphasized that the number of subjects is relatively small, and this investigation should therefore be considered as a pilot study.

Aims: To identify client characteristics that predict attendance at treatment sessions and to investigate the effect of attendance on outcomes using data from the UK Alcohol Treatment Trial., Methods: Logistic regression was used to determine whether there were characteristics that could predict attendance and then continuation in treatment. Linear regression was used to explore the effects of treatment attendance on outcomes., Results: There were significant positive relationships between treatment attendance and outcomes at Month 3. At Month 12, these relationships were only significant for dependence and alcohol problems for those randomized to motivational enhancement therapy (MET). There were significant differences between groups in attendance, with MET clients more likely to attend than clients allocated to social behaviour and network therapy (SBNT). MET clients were also more likely to attend all sessions (three sessions) compared with SBNT (eight sessions). MET clients with larger social networks and those with confidence in their ability not to drink excessively were more likely to attend. SBNT clients with greater motivation to change and those with more negative short-term alcohol outcome expectancies were more likely to attend. No significant predictors were found for retention in treatment for MET. For those receiving SBNT, fewer alcohol problems were associated with continuation in treatment., Conclusion: Attending more sessions was associated with better outcomes. An interpretation of these findings is that, to improve outcomes, methods should be developed and used to increase attendance rates. Different characteristics were identified that predicted attendance and continuation in treatment for MET and SBNT.

Aim: Sober alcoholic abusers exhibit personality traits such as novelty-seeking (NS) and sensation-seeking, which overlap to a limited extent. In parallel, they also show impaired executive and decision-making processes. However, little is known about the specific and common cognitive processes associated with NS and sensation-seeking personality traits in detoxified sober alcoholic abusers., Methods: In these present studies, we have investigated the relationships between executive functioning/central executive of working memory (pre-potent response inhibition, manipulation stored in working memory), and decision-making under uncertainty and NS/sensation-seeking traits in such alcoholics., Results: Compared with healthy controls (n = 30, mean age = 40.2), and in agreement with previous studies, alcoholics (n = 30, mean age = 40.4) showed higher levels of both NS and sensation-seeking traits. Alcoholics were also disadvantaged with respect to (a) gambling tasks, as reported previously, and (b) a poor ability to manipulate information stored in working memory and inhibit pre-potent responses. Most importantly, regression analyses and mediation analyses measures showed that poor response inhibition and decision-making were associated with high NS behaviour. In addition, impaired decision-making and manipulation of stored information in working memory were associated with a high sensation-seeking trait., Conclusions: Overall, these results support the existence of specific links between cognitive executive functioning, decision-making under uncertainty and NS/sensation-seeking personality traits in individuals with alcoholism.

Aims: This study determined the information about recent alcohol consumption obtained when urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) were introduced as a routine test in outpatient treatment programs for alcohol and drug dependence., Patients and Methods: Outpatients (21 men and 3 women) undergoing treatment for alcohol (N = 8) or drug (N = 10) dependence, or in methadone maintenance therapy (N = 6) volunteered for the study. Twice weekly in connection with return visits to the unit, patients gave a urine sample and completed an anonymous single-question form about any drinking in the past 3 days. Urinary EtG and EtS were determined by liquid chromatography-mass spectrometry., Results: Totally, 214 urine samples (4-14 samples/patient; mean 9) and 211 self-reports were collected over a 2-8-week period. Altogether 26% of the urine samples from 12 of 24 patients tested positive for EtG (0.5-434 mg/l) and/or EtS (0.1-87 mg/l). In one patient, samples were only positive for EtS. In 21% of 211 self-reports from 11 patients, alcohol ingestion was admitted in the past 3 days. In 87% of the 211 complete cases, the self-report information agreed with the EtG/EtS results (i.e. true positives and true negatives). The highest frequency of drinking was seen in the drug-dependent group with only 20% of the patients being abstinent according to both measures. This compares with 62.5% abstinence in the alcohol-dependent group and 50% in the methadone maintenance therapy group., Conclusion: Although based on a limited number of subjects, these results indicated that urinary EtG and EtS testing is a useful tool for objective identification of recent drinking in outpatients treated for alcohol and drug dependence.

Fatty acid ethyl esters (FAEE) are known to be a direct alcohol marker and are mainly investigated in hair samples for their ability to be incorporated into this matrix from sebum. The present study used an already developed methodology to provide and confirm information about the use of FAEEs in skin surface lipids as markers of alcohol consumption. The skin surface lipids were collected with Sebutapes(®) from the foreheads of teetotalers, light drinkers, social drinkers, and alcoholics. The samples were analyzed by direct solid-phase microextraction and gas chromatography-mass spectrometry for ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate. Relative FAEE/sebum allowed an evaluation of alcohol consumption. The ranges obtained for relative FAEEs in each category were as follows, teetotalers (0-13.85 pg/mg), light drinkers (11.10-26.80 pg/mg), social drinkers (20.55-86.55 pg/mg), and alcoholics (109.00-1243.40 pg/mg). A social drinker volunteer was monitored during a period of two months. The highest m(FAEE)/m(sebum) were generally detected 7-9 days after the days of high alcohol consumption. From these results, a clear distinction of teetotalers, social drinkers, and alcoholics could be established with the methodology used.

Aims: To compare the mortality of female alcoholics randomly assigned to the woman-only programme 'Early treatment for Women with Alcohol Addiction' (EWA) versus those who received mixed gender 'Treatment As Usual' (TAU)., Methods: Randomized controlled trial involving 2-year follow-up by personal interview and mortality register data through 27 years of 200 women first time treated for alcohol use disorder (AUD; EWA, n = 100 and TAU, n = 100), who were consecutively recruited during 1983-1984. Data from the Causes of Death Register were used to test for mortality differences related to group interaction predictors such as age, inpatient versus outpatient status at intake and 2-year drinking outcome., Results: Significantly lower mortality was found among younger women who participated in EWA compared with those who received TAU. This difference lasted nearly 20 years after intake to treatment. For women who only needed outpatient treatment, reduced mortality was found in the EWA group, even for older women. Increased mortality was found for TAU women who did not attend the 2-year follow-up compared with those who attended; no such difference was found for EWA women. This indicates different attrition mechanisms in the two groups. Thus, previously reported treatment effects may have been underestimated. EWA was a more comprehensive programme than TAU while also being single gender., Conclusions: EWA, specifically developed to meet a broad spectrum of problems among women with AUDs, was more effective than TAU, a mixed gender programme. It was not possible to separate whether this was in part because it was a more comprehensive programme, as well as being single gender.

Aims: This study aims to investigate sleep quality and the subjective dream experience in alcohol-dependent patients during withdrawal and abstinence compared with healthy controls., Methods: Thirty-seven patients with alcohol dependency and 35 healthy control subjects were asked to fill in several questionnaires and to give information about their subjective sleep and dream experiences. Twelve patients participated in a follow-up interview 4 weeks later., Results: Sleep quality is impaired in alcohol-dependent patients during detoxication, and the subjective dream experience is more negatively toned compared with healthy controls. Both sleep quality and dream experience improves slightly after 4 weeks of abstinence. Patients with alcohol dependency during withdrawal and abstinence dream significantly more often about alcohol. However, none of the abstinent alcohol-dependent patients dreamed about alcohol during withdrawal., Conclusions: This study shows that the subjective sleep and dream quality is strongly impaired in patients with alcohol dependency. Differences in the dream experience between alcohol-dependent patients and healthy controls are in accordance with the continuity hypotheses of dreaming. The hypothesis of dreaming about alcohol as a compensatory effect, however, could not be confirmed.

Aims: To examine the predictors and correlates of depression in alcoholic patients following detoxification and during outpatient treatment, and the role of acamprosate., Method: The international research program of acamprosate has involved 6500 patients in randomized, placebo-controlled trials. Extensive baseline and follow-up data were documented for each patient. An individual patient data meta-analysis was conducted on a partial database., Results: From 3354 patients in 11 studies (10 countries), we found 1120 (33.4% confidence intervals: 31.8-35.0) depressed patients (DPs). Among alcohol patients, the profile of DPs can be defined by five predictors: being female, younger, unemployed and living alone and being an episodic drinker. Compared with non-depressed patients (NDPs), their motivation to start a treatment and the compliance to treatment were lower. DPs performed less than NDPs in achieving abstinence. The acamprosate effect in increasing abstinence was similar for both DPs and NDPs patients. Abstinence during the trial was the key factor of depression remission: DPs were 7.58 times more likely to become NDPs if they were continuously abstinent., Conclusion: Our results justify the need to systematically identify depression among alcohol-dependent patients, but to treat the alcohol dependence as a first step, because enhancing abstinence will often involve remission of the depressive disorder.

Aims: To identify factors associated with retention in treatment of alcohol-dependent individuals and to compare treatment retention between men and women., Methods: Analysis of the treatment attendance records and baseline characteristics of 833 men and 218 women who undertook to attend follow-up treatment in an alcoholism treatment centre., Results: Retention after 4 weeks of treatment is more likely to occur among those using adjuvant medication (the most frequent of which was disulfiram), those presenting severe alcoholism and those who are older and tend to be frequent drinkers. There was no gender difference regarding treatment retention., Conclusion: Such results suggest possibilities for developing specific strategies to reduce the risk of early dropout from treatment.

Aims: To assess the effectiveness of procysteine (PRO) supplementation provided during a period of abstinence (ABS) on alcohol-induced skeletal muscle atrophy and oxidant stress., Methods: Age- and gender-matched Sprague-Dawley rats were fed the Lieber-DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 12 week. Next, subgroups of alcohol-fed rats were fed the control diet for 2 week (ABS) supplemented with either PRO (0.35%, w/v) or vehicle. Plantaris morphology was assessed by hematoxylin and eosin staining. Total, reduced and oxidized glutathione (GSH) levels and total antioxidant potential were determined by commercially available assay kits. Antibody arrays were used to determine cytokine levels. Real-time polymerase chain reaction was used to determine gene expressions of two E3 ubiquitin ligases, atrogin-1 and muscle ring finger protein-1 (MuRF-1)., Results: Plantaris muscles from alcohol-fed rats displayed extensive atrophy, as well as decreased GSH levels, a trend for decreased total antioxidant potential and elevated atrogin-1 and MuRF-1 mRNA levels. GSH levels and total antioxidant potential continued to decrease during 2 weeks of ABS from alcohol, which were normalized in abstinent rats provided PRO. Gene levels of both E3 ligases returned to baseline during ABS. In parallel, plantaris cross-sectional area increased in both groups during ABS., Conclusions: PRO supplementation during ABS significantly attenuated alcohol-induced redox stress compared with untreated abstinent rats. Thus, our data may suggest that GSH restoration therapy may provide therapeutic benefits to the overall antioxidant state of skeletal muscle when prescribed in conjunction with an established detoxification program for recovering alcoholics.

Aims: Dangerous alcohol consumption practices are common in adolescents, yet little is known about their consequences on attainment of peak bone mass and long-term skeletal integrity. We previously demonstrated that binge alcohol-exposed adolescent rats showed site-specific reductions in accruement of bone mineral density and bone strength, which were incompletely recovered following prolonged alcohol abstinence. Currently, we analysed the vertebral transcriptome of adolescent rats following alcohol treatment and abstinence to identify long-term molecular changes in the lumbar spine., Methods: Sixty male adolescent Sprague-Dawley rats were assigned to one of six treatment groups receiving binge alcohol (3 g/kg) or saline i.p., 3 consecutive days (acute binge), 4 consecutive weekly (3-day) binge cycles (chronic binge) or 4 weekly binge cycles followed by a 30-day abstinence period (chronic binge with abstinence). Following treatment, lumbar vertebrae were assayed for global transcriptional changes using gene array technology., Results: Analysis of the adolescent rat vertebral transcriptome identified clusters of binge alcohol-sensitive genes displaying differential expression patterns starting before bone damage was seen and persisting after alcohol treatment was discontinued. Functional grouping of these gene clusters identified candidate cellular pathways affected following acute and chronic binge treatment, as well as pathways remaining modulated following abstinence., Conclusions: These results demonstrate that binge alcohol exposure can produce disruptions of normal bone gene expression patterns in the adolescent rat that persist well beyond the period of active intoxication. This data may have relevance to peak bone mass attainment and future risk of skeletal disease in adolescents engaging in repeated binge-drinking episodes.

Alcohol dependence leads to persistent neuroadaptations, potentially related to structural plasticity. Previous work has shown that hippocampal neurogenesis is modulated by alcohol, but effects of chronic alcohol on neurogenesis in the forebrain subventricular zone (SVZ) have not been reported. Effects in this region may be relevant for the impairments in olfactory discrimination present in alcoholism. Here, we examined the effects of prolonged alcohol dependence on neurogenesis. Rats were sacrificed directly after 7 wk of intermittent alcohol vapour exposure, or 3, 7 or 21 d into abstinence. Proliferation was assessed using BrdU and Ki67 immunoreactivity, newly differentiated neurons (neurogenesis) as doublecortin-immunoreactivity (DCX-IR), and neural stem cells using the SOX2 marker. In the dentate gyrus, chronic dependence resulted in a pattern similar to that previously reported for acute alcohol exposure: proliferation and neurogenesis were suppressed by the end of exposure, rebounded on day 3 of abstinence, and returned to control levels by days 7 and 21. In the SVZ, proliferation was also suppressed at the end of alcohol exposure, followed by a proliferation burst 3 d into abstinence. However, in this area, there was a trend for reduced proliferation on days 7 and 21 of abstinence, and this was accompanied by significant suppression of DCX-IR, indicating a long-term suppression of forebrain neurogenesis. Finally, a decrease in the SOX2 stem cell marker was detected at days 7 and 21, suggesting long-term reduction of the SVZ stem cell pool. While suppression of hippocampal neurogenesis by alcohol dependence is transient, the suppression in the forebrain SVZ appears long-lasting.

Aims: To compare the long-term effectiveness of acamprosate (ACP) and disulfiram (DSF) in the treatment of alcohol dependence and their effectiveness in regard to patient characteristics, within a naturalistic outpatient treatment setting., Method: Retrospective data from 2002 to 2007 were analysed on 353 alcohol-dependent subjects in outpatient treatment, who, according to the patient's and the clinician's mutual decision, received either supervised DSF (with thrice-weekly appointments) or ACP (once-weekly appointments) following an inpatient alcohol detoxification treatment. Abstinence was assessed by alcohol breathalyzer, patients' self-report, urine and serum analyses, and overall physicians' rating., Results: Baseline data in terms of current addictive behaviour and course of disease differed between groups to the disadvantage of the DSF group; compared to the ACP group, subjects treated with DSF showed a longer duration of alcohol dependence, higher amounts of daily alcohol consumption and more alcohol detoxification treatments in their history. In follow-up, Kaplan-Meier survival analysis revealed significant differences between groups in the primary and secondary measures of outcome (P always <0.01). Time elapsed before the first alcohol relapse as well as attendance to outpatient treatment and cumulative alcohol abstinence achieved within outpatient treatment was explicitly longer in the DSF group. A longer duration of alcohol dependence predicted a favourable treatment outcome in the DSF group, while for the ACP group the chances for a successful treatment increased with shorter duration of alcohol dependence., Conclusions: This study supports the thesis that supervised DSF is an important component of alcoholism treatment, and it appears to be more effective than the treatment with ACP particularly in patients with a long duration of alcohol dependence.

Most previous neuroimaging studies of alcohol-induced brain injury and recovery thereof during abstinence from alcohol used a single imaging modality. They have demonstrated widespread microstructural, macrostructural or metabolite abnormalities that were partially reversible with abstinence, with the cigarette smoking potentially modulating these processes. The goals of this study were to evaluate white matter injury and recovery thereof, simultaneously with diffusion tensor imaging, magnetic resonance imaging and spectroscopy in the same cohort; and to evaluate the relationships between outcome measures of similar regions. We scanned 16 non-smoking and 20 smoking alcohol-dependent individuals at 1 week of abstinence from alcohol and 22 non-smoking light drinkers using a 1.5 T magnetic resonance scanner. Ten non-smoking alcohol-dependent individuals and 11 smoking alcohol-dependent individuals were re-scanned at 1 month of abstinence. All regional diffusion tensor imaging, magnetic resonance imaging and spectroscopic outcome measures were calculated over comparable volumes of frontal, temporal, parietal and occipital white matter. At 1 week of abstinence and relative to non-smoking light drinkers, non-smoking alcohol-dependent individuals had higher mean diffusivity in frontal, temporal and parietal white matter (all P<0.008), whereas smoking alcohol-dependent individuals had elevated mean diffusivity only in frontal white matter (P=0.03). Smoking alcohol-dependent individuals demonstrated lower concentrations of N-acetyl-aspartate (a marker of neuronal viability) in frontal white matter (P=0.03), whereas non-smoking alcohol-dependent individuals had lower N-acetyl-aspartate in parietal white matter (P=0.05). These abnormalities were not accompanied by detectable white matter atrophy. However, the patterns of white matter recovery were different between non-smoking alcohol-dependent individuals and smoking alcohol-dependent individuals. In non-smoking alcohol-dependent individuals, the increase in fractional anisotropy of temporal white matter (P=0.003) was accompanied by a pattern of decreases mean diffusivity in all regions over 1 month of abstinence; no corresponding changes were observed in smoking alcohol-dependent individuals. In contrast, a pattern of white matter volume increase in frontal and temporal lobes was apparent in smoking alcohol-dependent individuals but not in non-smoking alcohol-dependent individuals. These results were not accompanied by significant changes in metabolite concentrations. Finally, there were no consistent patterns of association between measures obtained with different imaging modalities, either cross-sectionally or longitudinally. These data demonstrate significant white matter improvements with abstinence from alcohol, reflected either as microstructural recovery or volumetric increases that depend on the smoking status of the participants. We believe our results to be important, as they demonstrate that use of a single imaging modality provides an incomplete picture of neurobiological processes associated with alcohol-induced brain injury and recovery thereof that may even lead to improper interpretation of results.

Aims: The aim of this study was to analyse initial orienting processes as well as maintenance of attention towards alcohol cues in recently detoxified alcoholics and light social drinkers. Furthermore, we investigated the influence of pre-treatment alcohol consumption and abstinence duration onto alcohol-related attentional bias., Methods: We used an alcohol-visual-dot-probe-task with two different stimulus onset asynchronies (SOA) to examine processes of initial orienting and maintenance of attention separately (50 and 500 ms SOA)., Results: With short SOA, we found a positive attentional bias towards alcohol cues in alcohol-dependent patients and light social drinkers that was positively associated with pre-treatment alcohol consumption in alcoholics. Using a longer SOA, a negative attentional bias was found in light social drinkers and in patients abstinent for more than 2 weeks indicating alcohol stimuli avoidance. In patients, we found a negative correlation between attentional bias and duration of abstinence., Conclusions: After initial visual orienting towards alcohol-related stimuli, light social drinkers as well as longer abstinent alcohol-dependent patients disengage their attention. In patients, this disengagement increased during the first 3 weeks after detoxification indicating assimilation to the attentional bias pattern of light social drinkers.

Aims: The aims of this study were to assess bone mineral density (BMD) and content (BMC), osteocalcin, serum telopeptide, PTH and vitamin D in alcoholics, and to determine if a 6-month period of abstinence leads to changes in these parameters., Methods: Serum osteocalcin, insulin-like growth factor 1 (IGF-1), telopeptide (40 patients) and 1,25 dihydroxyvitamin D, were measured in 28 controls and 77 alcoholic patients, 48 of whom were evaluated again 6 months later. All patients underwent whole-body assessment of BMD by a Hologic QDR-2000 (Waltham, MA, USA) bone densitometer, at the beginning of the study and 6 months later., Results: Patients showed higher serum telopeptide levels (0.59 +/- 0.40 versus 0.19 +/- 0.10 nmol/100 ml, P < 0.001), lower IGF-1 [median = 49, interquartile range (IQR) = 31-121 ng/ml versus 135, IQR = 116-237 ng/ml, P < 0.001], vitamin D [26.5, IQR = 17.0-37.8 pg/ml versus 82.4 (IQR = 60.9-107.4 pg/ml, P < 0.001] and osteocalcin (2.1, IQR = 1.1-3.6 ng/ml versus 6.65, IQR = 4.9-8.8 ng/ml, P < 0.001) than those in controls. Patients also showed lower BMD values, Z- and T-scores at many levels of the skeleton and reduced total BMC. After 6 months, those who continued drinking showed a loss of bone mass, whereas those who abstained showed either no change or increase, differences being especially marked at pelvis, right arm and total BMD and BMC. Simultaneously, abstainers showed a significant increase in osteocalcin (versus a decrease among those who continued drinking). Serum telopeptide increased in both groups., Conclusion: Ethanol consumption leads to osteopenia, and decreased serum osteocalcin, which improve with abstinence, whereas those who continue drinking show a worsening of both parameters.

Aims: Although a wide variety of biomarkers reflecting liver status are known to be influenced by excessive ethanol consumption, the dose-response relationships between ethanol intake and marker changes have remained less understood., Methods: Serum gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, and ferritin and albumin protein concentrations were compared in a large population of heavy drinkers (105 men, 28 women), moderate drinkers (781 men, 723 women) and abstainers (252 men, 433 women), who were devoid of apparent liver disease., Results: In heavy drinkers, serum GGT, AST, ALT, ferritin and albumin were all significantly higher than in moderate drinkers or abstainers (P < 0.001 for all comparisons). The highest incidences of elevated values were found for GGT (62%) followed by AST (53%), ALT (39%), ferritin (34%) and albumin (20%). Serum GGT (P < 0.001), ALT (P < 0.01) and ferritin (P < 0.05) in moderate drinkers were also higher than the levels observed in abstainers. When the study population was further divided into subgroups according to gender, significant differences between moderate drinkers and abstainers in GGT and ALT were noted in men whereas not in women., Conclusions: The data demonstrate that biomarkers of alcohol abuse and liver function may respond to even rather low levels of ethanol intake in a gender-dependent manner, which should be implicated in studies on the early-phase interactions of ethanol and the liver and in the definition of normal ranges for such biomarkers.

Aims: This is a review of preclinical studies covering alcohol-induced brain neuronal death and loss of neurogenesis as well as abstinence-induced brain cell genesis, e.g. brain regeneration. Efforts are made to relate preclinical studies to human studies., Methods: The studies described are preclinical rat experiments using a 4-day binge ethanol treatment known to induce physical dependence to ethanol. Neurodegeneration and cognitive deficits following binge treatment mimic the mild degeneration and cognitive deficits found in humans. Various histological methods are used to follow brain regional degeneration and regeneration., Results: Alcohol-induced degeneration occurs due to neuronal death during alcohol intoxication. Neuronal death is related to increases in oxidative stress in brain that coincide with the induction of proinflammatory cytokines and oxidative enzymes that insult brain. Degeneration is associated with increased NF-kappaB proinflammatory transcription and decreased CREB transcription. Corticolimbic brain regions are most sensitive to binge-induced degeneration and induce relearning deficits. Drugs that block oxidative stress and NF-kappaB transcription or increase CREB transcription block binge-induced neurodegeneration, inhibition of neurogenesis and proinflammatory enzyme induction. Regeneration of brain occurs during abstinence following binge ethanol treatment. Bursts of proliferating cells occur across multiple brain regions, with many new microglia across brain after months of abstinence and many new neurons in neurogenic hippocampal dentate gyrus. Brain regeneration may be important to sustain abstinence in humans., Conclusions: Alcohol-induced neurodegeneration occurs primarily during intoxication and is related to increased oxidative stress and proinflammatory proteins that are neurotoxic. Abstinence after binge ethanol intoxication results in brain cell genesis that could contribute to the return of brain function and structure found in abstinent humans.

Aims: The reduction of habitual alcohol drinking is recommended for the prevention of hypertension. Daily or weekly alcohol consumption, which is used for evaluation of the effects of alcohol drinking on blood pressure, is usually not corrected by body weight. In this study, the influence of body weight on the relationship between alcohol intake and blood pressure was investigated., Methods: The subjects (27,005 healthy men at ages of 35-54 years) were divided into four groups by average daily ethanol intake [non-, light (<15 g per day), moderate (>or=15 and <30 g per day) and heavy (>or=30 g per day) drinkers]. The subjects were also divided into four quartile groups by body weight., Results: Alcohol intake and the percentage of drinkers were not different in the four quartile groups of body weight. In the first and second quartiles of body weight, systolic and diastolic blood pressures were significantly higher in moderate and heavy drinkers than in non-drinkers, while systolic and diastolic blood pressures in the fourth quartile of body weight were significantly higher in heavy drinkers than in non-drinkers but were not significantly different in moderate drinkers and non-drinkers. The differences in systolic or diastolic blood pressure between non-drinkers and moderate drinkers and between non-drinkers and heavy drinkers became greater as body weight decreased. These results were not altered when age and smoking history were adjusted., Conclusions: The results suggest that body weight modifies the relationship between alcohol consumption and blood pressure and thus should be taken into account when effects of alcohol on blood pressure are considered.

Aims: The aims of this study were to investigate the performance of the treatment version of the Readiness to Change Questionnaire (RCQ[TV]) among individuals currently receiving alcohol detoxification and to develop a treatment version of the Treatment Readiness Tool (TReaT[TV])., Methods: A total of 549 patients (86% men) recruited from two detoxification units were interviewed close to treatment intake and followed up 12 months later. Confirmatory factor analyses and logistic regression analyses were conducted., Results: A modified nine-item version of the RCQ[TV] showed a good fit of the model (CFI = 0.95) and internal consistencies ranging between 0.49 and 0.91. Twelve months later, RCQ-Actors had an odds ratio of 1.95 (95% CI: 1.12-3.37) for being abstinent compared to Precontemplators/Contemplators. The development of the TReaT[TV] resulted in 15 items and 5 scales with a CFI of 0.97 and Cronbach's alphas ranging between 0.59 and 0.94. TReaT[TV] Precontemplators/Contemplators were less likely to utilize help than Maintainers (OR = 0.17, 95% CI: 0.06-0.45)., Conclusions: The psychometric properties were modest for the modified RCQ[TV] and good for the TReaT[TV]. Readiness to change and readiness to seek help should be assessed separately among treatment seekers.

In adults, light to moderate alcohol consumption is associated with lower risks for heart disease, diabetes, and mortality. This study examined whether light to moderate alcohol use is also associated with lower risk of incident physical disability over two 5-year periods in 4,276 noninstitutionalized adults in the United States, aged 50 years or older, by using data from 3 waves of the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study surveys from 1982 to 1992. Light/moderate drinking (<15 drinks per week and <5 per drinking day or 4 per drinking day for women) was associated with reduced risk for incident disability or death over 5 years, compared with abstention (adjusted odds ratio = 0.77; P = 0.008). Among survivors, light/moderate drinking was associated with lower risk for incident disability, compared with abstention (adjusted odds ratio = 0.75; P = 0.009). In stratified analyses, disability risk decreased with light/moderate drinking in a dose-dependent fashion in men and women with good or better self-reported health but not in men or women with fair or worse self-reported health. Alcohol consumption in moderation might reduce the risk of developing physical disability in older adults in good health but not in those in poor health.

Aims: The aim of this study was to investigate longitudinal changes in quality of life (QOL) as a function of transitions in alcohol use disorders (AUD) over a 3-year follow-up of a general US population sample., Methods: The analysis is based on individuals who drank alcohol in the year preceding the Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions and were reinterviewed at Wave 2 (n = 22,245). Using multiple linear regression models, changes in SF-12 QOL were estimated as a function of DSM-IV AUD transitions, controlling for baseline QOL and multiple potential confounders., Results: Onset and offset of AUD were strongly associated with changes in mental/psychological functioning, with significant decreases in mental component summary (NBMCS) scores among individuals who developed dependence and significant increases among those who achieved full and partial remission from dependence. The increases in overall NBMCS and its social functioning, role emotional and mental health components were equally great for abstinent and nonabstinent remission from dependence, but improvements in bodily pain and general health were associated with nonabstinent remission only. Onset of abuse was unrelated to changes in QOL, and the increase in NBMCS associated with nonabstinent remission from abuse only was slight. Individuals with abuse only or no AUD who stopped drinking had significant declines in QOL., Conclusions: These results suggest the possible importance of preventing and treating AUD for maintaining and/or improving QOL. They are also consistent with the sick quitter hypothesis and suggest that abuse is less a mental disorder than a maladaptive pattern of behavior.

Aims: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugated ethanol metabolites formed in low amounts after alcohol consumption. Compared with ethanol, EtG and EtS are excreted in urine for a prolonged time, making them useful as sensitive alcohol biomarkers. This study determined the detection times for EtG and EtS in alcoholic patients undergoing alcohol detoxification., Methods: Alcohol-dependent patients (n = 32) with an initial alcohol concentration >or=1 g/L based on breath testing were followed during detoxification. Urine samples for determination of EtG, EtS, ethanol and creatinine were collected on admission to the hospital and thereafter once daily for several days. EtG and EtS measurements were performed by liquid chromatography-mass spectrometry (LC-MS) and EtG also using an immunochemical assay (DRI-EtG EIA, ThermoFisher/Microgenics)., Results: The detection time for urinary EtG was weakly correlated (r = 0.434, P = 0.013) with the initial alcohol concentration (range 1.0-3.4 g/L). For EtG, the individual time range until return to below the applied cut-off limit (<0.5 mg/L) was approximately 40-130 h (median 78) with a similar time course observed for EtS. After correction for urine dilution, the time until an EtG/creatinine ratio <0.5 mg/g was approximately 40- 90 h (median 65). The detection times after an estimated zero ethanol concentration were approximately 30-110 h (median 66) for EtG and approximately 30- 70 h (median 56) for EtG/creatinine. The EtG results by LC-MS and the immunoassay were in good agreement., Conclusions: During alcohol detoxification, EtG and EtS remained detectable in urine for several days. The detection times showed wide inter-individual variations, also after adjusting values for urine dilution and to the estimated times for a completed ethanol elimination.