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1.  Transitions In and Out of Alcohol Use Disorders: Their Associations with Conditional Changes in Quality of Life Over a 3-Year Follow-Up Interval† 
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.
PMCID: PMC2605522  PMID: 19042925
2.  Breath Alcohol Estimation Training: Behavioral Effects and Predictors of Success 
Aims: Breath alcohol concentration (BrAC) estimation training has been effective in increasing estimation accuracy in social drinkers. Predictors of estimation accuracy may identify populations to target for training, yet potential predictors typically are not evaluated. In addition, the therapeutic efficacy of estimation training as a preventive strategy for problematic drinking is unknown. Methods: Forty-six social drinkers with a recent binge history were randomly assigned to an intervention or control group (n = 23 per group). In each of three sessions (pretraining, training, testing), participants consumed alcohol (0.32, 0.24, 0.16 and 0.08 g/kg, in random order) every 30 min (total dose: 0.8 g/kg). Participants provided five BrAC estimates within 3 h of alcohol administration. The intervention group, but not control group, received internal and external training. During testing, participants provided BrAC estimates, but received no feedback. Participants returned for two follow-up visits to complete self-report measures. Results: BrAC estimation training improved intervention group estimation accuracy within the laboratory. Together, training, low trait anxiety and low risk expectancy predicted high testing accuracy. There were no significant group differences in subsequent alcohol consumption, behavior under the influence or risk expectancy regarding potentially hazardous behaviors. Conclusion: BrAC estimation training is effective in the laboratory but may not translate into naturalistic settings.
PMCID: PMC3685329  PMID: 23695976
3.  Awareness and Treatment of Alcohol Dependence in Japan: Results from Internet-Based Surveys in Persons, Family, Physicians and Society 
Aims: To understand current awareness of, and views on, treatment of alcohol dependence in Japan. Methods: (a) Nationwide internet-based survey of 520 individuals, consisting of 52 diagnosed alcohol-dependent (AD) persons, 154 potentially alcohol-dependent (ADP) persons, 104 family members and 106 friends/colleagues of AD persons, and 104 general individuals, derived from a consumer panel where the response rate was 64.3%. We enquired into awareness about the treatment of alcohol dependence and patient pathways through the healthcare network. (b) Nationwide internet-based survey of physicians (response rate 10.1% (2395/23,695) to ask 200 physicians about their management of alcohol use disorders). Results: We deduced that 10% of alcohol-dependent Japanese persons had ever been diagnosed with alcohol dependence, with only 3% ever treated. Regarding putative treatment goals, 20–25% of the AD and ADP persons would prefer to attempt to abstain, while 60–75% preferred ‘reduced drinking.’ A half of the responding physicians considered abstinence as the primary treatment goal in alcohol dependence, while 76% considered reduced drinking as an acceptable goal. Conclusion: AD and ADP persons in Japan have low ‘disease awareness’ defined as ‘understanding of signs, symptoms and consequences of alcohol use disorders,’ which is in line with the overseas situation. The Japanese drinking culture and stigma toward alcohol dependence may contribute to such low disease awareness and current challenging treatment environment. While abstinence remains the preferred treatment goal among physicians, reduced drinking seems to be an acceptable alternative treatment goal to many persons and physicians in Japan.
PMCID: PMC4060736  PMID: 24893604
4.  Evaluating the Effects of the Introduction of Off-Sale Alcohol Outlets on Violent Crime 
Aims: To examine the effects on violence of a policy change that ended prohibition of off-sale alcohol outlets in Lubbock, Texas. Methods: Time-series analysis of violent crime data from police records comparing the periods before and after the policy change. Results: The effect of the policy change on both total violent crime and aggregated assault was small and did not approach statistical significance. Conclusions: Increased availability of alcohol through off-sale premises may not influence the type of violence reported to the police in Lubbock, Texas.
PMCID: PMC3633363  PMID: 23455369
5.  Cardiovascular Responses and Differential Changes in Mitogen-Activated Protein Kinases Following Repeated Episodes of Binge Drinking 
Aims: Excessive alcohol use in the form of binge drinking is associated with many adverse medical outcomes. Using an animal model, the primary objective of this study was to determine the effects of repeated episodes of binge drinking on myocardial structure, blood pressure (BP) and activation of mitogen-activated protein kinases (MAPKs). The effects of carvedilol, a beta-adrenergic blocker, were also examined in this animal model of binge drinking. Methods: Rats were randomized into three groups: control, binge and binge + carvedilol (20 mg/kg). Animals received intragastric administration of 5 g ethanol/kg in the morning × 4 days (Monday–Thursday) followed by no ethanol on Friday–Sunday. Animals were maintained on the protocol for 5 weeks. BP was measured using radiotelemetry methods. Animals underwent echocardiography at baseline, 2.5 and 5 weeks. Myocardial MAPKs were analyzed at 5 weeks using western blot techniques. Results: Over the course of 5 weeks, binge drinking was associated with significant transient increases in BP that were greater at 4 and 5 weeks compared with earlier time points. Carvedilol treatment significantly attenuated the binge-induced transient increases in BP at 4 and 5 weeks. No significant changes were found in echocardiographic parameters at any time period; however, binge drinking was associated with increased phosphorylation of p38 MAPK, which was blocked by carvedilol treatment. Conclusion: Repeated episodes of binge drinking result in progressive and transient increases in BP, no change in myocardial structure and differential regulation of MAPK activation.
PMCID: PMC3571203  PMID: 22878590
6.  Direct Central Nervous System Effect of Alcohol Alters Synthesis and Degradation of Skeletal Muscle Protein 
Aims: Alcohol can directly impair protein synthesis in cultured myocytes as well as in in situ perfused skeletal muscle. However, alcohol in the general circulation diffuses rapidly into the central nervous system (CNS). Therefore, this study determined whether localized elevation of alcohol within the CNS is capable of decreasing muscle protein synthesis. Methods: Conscious unstrained male rats received a continuous intracerebroventricular (ICV) infusion of ethanol and skeletal muscle protein synthesis and degradation were assessed. Results: ICV alcohol decreased protein synthesis in the gastrocnemius after 6 and 24 h, compared with the time-matched controls. The reduction was equivalent for both sarcoplasmic and myofibrillar proteins and was reversible. The inhibitory effect of alcohol was not prevented by the catalase inhibitor 3-amino-1,2,4-triazole and was mimicked by ICV-administered t-butanol. The alcohol-induced decrease in muscle protein synthesis was associated with a concomitant reduction in phosphorylation of 4E-binding protein and ribosomal S6 kinase-1, suggesting impaired mammalian target of rapamycin kinase activity. ICV alcohol also impaired the ability of leucine to stimulate protein synthesis. Conversely, ICV alcohol increased muscle proteasome activity and muscle RING-finger protein-1 mRNA content. Altered muscle protein metabolism was not associated with changes in muscle mRNA content for tumor necrosis factor α, interleukin-6 or insulin-like growth factor (IGF)-I or circulating insulin or IGF-I. Conclusion: Selective elevation of alcohol within the CNS is capable of decreasing protein synthesis and increasing protein degradation in muscle in the absence of alcohol in the general circulation, thus revealing a previously unrecognized central neural mechanism, which may account for part of the inhibitory effect of ingested alcohol on muscle protein homeostasis.
PMCID: PMC3571205  PMID: 23079499
7.  Rare ADH Variant Constellations are Specific for Alcohol Dependence 
Aims: Some of the well-known functional alcohol dehydrogenase (ADH) gene variants (e.g. ADH1B*2, ADH1B*3 and ADH1C*2) that significantly affect the risk of alcohol dependence are rare variants in most populations. In the present study, we comprehensively examined the associations between rare ADH variants [minor allele frequency (MAF) <0.05] and alcohol dependence, with several other neuropsychiatric and neurological disorders as reference. Methods: A total of 49,358 subjects in 22 independent cohorts with 11 different neuropsychiatric and neurological disorders were analyzed, including 3 cohorts with alcohol dependence. The entire ADH gene cluster (ADH7–ADH1C–ADH1B–ADH1A–ADH6–ADH4–ADH5 at Chr4) was imputed in all samples using the same reference panels that included whole-genome sequencing data. We stringently cleaned the phenotype and genotype data to obtain a total of 870 single nucleotide polymorphisms with 0< MAF <0.05 for association analysis. Results: We found that a rare variant constellation across the entire ADH gene cluster was significantly associated with alcohol dependence in European-Americans (Fp1: simulated global P = 0.045), European-Australians (Fp5: global P = 0.027; collapsing: P = 0.038) and African-Americans (Fp5: global P = 0.050; collapsing: P = 0.038), but not with any other neuropsychiatric disease. Association signals in this region came principally from ADH6, ADH7, ADH1B and ADH1C. In particular, a rare ADH6 variant constellation showed a replicable association with alcohol dependence across these three independent cohorts. No individual rare variants were statistically significantly associated with any disease examined after group- and region-wide correction for multiple comparisons. Conclusion: We conclude that rare ADH variants are specific for alcohol dependence. The ADH gene cluster may harbor a causal variant(s) for alcohol dependence.
PMCID: PMC3523382  PMID: 23019235
8.  Alcohol Exposure During Late Adolescence Increases Drinking in Adult Wistar Rats, an Effect that is not Reduced by Finasteride 
Aims: We tested whether an exposure to alcohol in late adolescence, an age of rapid increase in neuroactive steroid precursors, would increase voluntary alcohol consumption in adult rats and whether this effect would be modulated by finasteride, an inhibitor of neuroactive steroid synthesis. Methods: In Experiment 1, we exposed male Wistar rats to 8% alcohol during the dark cycle for 1 week during late adolescence [postnatal days (PNDs) 51–58], and then measured voluntary alcohol consumption 1 month later in adulthood (PNDs 91–104). In Experiment 2, finasteride was administered during the forced alcohol exposure in late adolescence and, in Experiment 3, during voluntary alcohol consumption in adulthood. Plasma was collected at the end of each finasteride treatment to confirm the reduction of plasma neuroactive steroid levels. Results: We found that a daily 12-h exposure to alcohol for 7 days in late adolescence significantly increased voluntary alcohol consumption (4-fold) a month later during adulthood. Finasteride administration in late adolescence increased group alcohol intake in late adolescence but did not block the effect of adolescent alcohol exposure on increasing alcohol preference in adulthood. There was no effect of finasteride treatment in adulthood on alcohol preference. Conclusions: A daily 12-h exposure to alcohol for 7 days in late adolescence was sufficient to induce chronically increased alcohol preference in adulthood, indicating that this age may be sensitive to the effects of alcohol.
PMCID: PMC3523383  PMID: 22997410
9.  Insulin Resistance, Ceramide Accumulation and Endoplasmic Reticulum Stress in Experimental Chronic Alcohol-Induced Steatohepatitis 
Aims: Chronic alcohol abuse causes steatohepatitis with insulin resistance, which impairs hepatocellular growth, survival and metabolism. However, growing evidence supports the concept that progressive alcohol-related liver injury may be mediated by concurrent mal-signaling through other networks that promote insulin resistance, e.g. pro-inflammatory, pro-ceramide and endoplasmic reticulum (ER) stress cascades. Methods: Using the Long Evans rat model of chronic ethanol feeding, we characterized the histopathologic and ultrastructural features of steatohepatitis in relation to biochemical and molecular indices of tissue injury, inflammation, insulin resistance, dysregulated lipid metabolism and ER stress. Results: Chronic steatohepatitis with early chicken-wire fibrosis was associated with enlargement of mitochondria and disruption of ER structure by electron microscopy, elevated indices of lipid storage, lipid peroxidation and DNA damage, increased activation of pro-inflammatory cytokines, impaired signaling through the insulin receptor (InR), InR substrate-1, Akt, ribosomal protein S6 kinase and proline-rich Akt substrate 40 kDa, glycogen synthase kinase 3β activation and constitutive up-regulation of ceramide and ER stress-related genes. Liquid chromatography coupled with tandem mass spectrometry demonstrated altered ceramide profiles with higher levels of C14 and C18, and reduced C16 species in ethanol-exposed livers. Conclusion: The histopathologic and ultrastructural abnormalities in chronic alcohol-related steatohepatitis are associated with persistent hepatic insulin resistance and pro-inflammatory cytokine activation, dysregulated lipid metabolism with altered ceramide profiles and both ER and oxidative stress. Corresponding increases in lipid peroxidation, DNA damage and protein carbonylation may have contributed to the chronicity and progression of disease. The findings herein suggest that multi-pronged therapeutic strategies may be needed for effective treatment of chronic alcoholic liver disease in humans.
PMCID: PMC3523384  PMID: 22997409
10.  Hair Ethyl Glucuronide is Highly Sensitive and Specific for Detecting Moderate-to-Heavy Drinking in Patients with Liver Disease 
Aims: Hair ethyl glucuronide (EtG) is a promising biomarker of moderate-to-heavy alcohol consumption and may have utility in detecting and monitoring alcohol use in clinical populations where alcohol use is of particular importance. This study evaluated the relationship between hair EtG and drinking in patients with liver disease. Methods: The subjects (n = 200) were patients with liver disease who presented for care at a university medical center. Alcohol use during the 3 months preceding participation in the study was assessed, and a sample of hair was obtained for EtG testing. Classification of drinking status (any drinking or averaging at least 28 g per day) by hair EtG was evaluated, as well as the effects of liver disease severity and demographic and hair care factors. Results: The area under the receiver operating characteristic curve for detecting an average of 28 g or more per day during the prior 90 days was 0.93. The corresponding sensitivity and specificity of hair EtG ≥8 pg/mg for averaging at least 28 g of ethanol per day were 92 and 87%, respectively. Cirrhosis and gender may have a modest influence on the relationship between drinking and hair EtG. Conclusion: Hair EtG was highly accurate in differentiating subjects with liver disease averaging at least 28 g of ethanol per day from abstainers and lighter drinkers.
PMCID: PMC3523385  PMID: 23015609
11.  How Might the Alcohol Minimum Unit Pricing (MUP) Impact upon Local Off-Sales Shops and the Communities Which They Serve? 
Aims: The aim of the study was to assess the likely impact of the Scottish Government's proposed alcohol minimum unit pricing (MUP) policy on community off-sales outlets (convenience stores or corner shops), and, in turn, on the local people who purchase drinks at such premises. This research adds to our knowledge by linking sales of alcohol products which will be affected by MUP (e.g. at the proposed 50 ppu) to the types of communities where these are the ‘drinks-of-choice’. Methods: A survey of independent community off-sales operating within the city of Glasgow, Scotland (n = 271) returned 144 completed questionnaires enquiring about each shop's customer base, best-selling alcohol products and participating shopkeepers' views on MUP. Responses were measured against current alcohol product prices (i.e. whether potentially affected by MUP) and local levels of socio-economic deprivation. Results: Participating shopkeepers were divided in their support for MUP, although more were in favour than against. Support for MUP tended to be rooted in business concerns. A majority reported having at least one best-selling alcohol product which will be affected by the proposed MUP policy at current prices, with the beverages that would be most affected (e.g. white cider) tending to be best-sellers at shops serving deprived communities. Conclusion: MUP is likely to impact most in socio-economically deprived communities. This is also where alcohol-related health and other inequalities are currently greatest.
PMCID: PMC3865818  PMID: 24293505
12.  Exposure of Children and Adolescents to Alcohol Marketing on Social Media Websites 
Aims: In 2011, online marketing became the largest marketing channel in the UK, overtaking television for the first time. This study aimed to describe the exposure of children and young adults to alcohol marketing on social media websites in the UK. Methods: We used commercially available data on the three most used social media websites among young people in the UK, from December 2010 to May 2011. We analysed by age (6–14 years; 15–24 years) and gender the reach (proportion of internet users who used the site in each month) and impressions (number of individual pages viewed on the site in each month) for Facebook, YouTube and Twitter. We further analysed case studies of five alcohol brands to assess the marketer-generated brand content available on Facebook, YouTube and Twitter in February and March 2012. Results: Facebook was the social media site with the highest reach, with an average monthly reach of 89% of males and 91% of females aged 15–24. YouTube had a similar average monthly reach while Twitter had a considerably lower usage in the age groups studied. All five of the alcohol brands studied maintained a Facebook page, Twitter page and YouTube channel, with varying levels of user engagement. Facebook pages could not be accessed by an under-18 user, but in most cases YouTube content and Twitter content could be accessed by those of all ages. Conclusion: The rise in online marketing of alcohol and the high use of social media websites by young people suggests that this is an area requiring further monitoring and regulation.
PMCID: PMC3932831  PMID: 24293506
13.  The Impact of Brief Alcohol Interventions in Primary Healthcare: A Systematic Review of Reviews 
Aims: The aim of the study was to assess the cumulative evidence on the effectiveness of brief alcohol interventions in primary healthcare in order to highlight key knowledge gaps for further research. Methods: An overview of systematic reviews and meta-analyses of the effectiveness of brief alcohol intervention in primary healthcare published between 2002 and 2012. Findings: Twenty-four systematic reviews met the eligibility criteria (covering a total of 56 randomized controlled trials reported across 80 papers). Across the included studies, it was consistently reported that brief intervention was effective for addressing hazardous and harmful drinking in primary healthcare, particularly in middle-aged, male drinkers. Evidence gaps included: brief intervention effectiveness in key groups (women, older and younger drinkers, minority ethnic groups, dependent/co-morbid drinkers and those living in transitional and developing countries); and the optimum brief intervention length and frequency to maintain longer-term effectiveness. Conclusion: This overview highlights the large volume of primarily positive evidence supporting brief alcohol intervention effects as well as some unanswered questions with regards to the effectiveness of brief alcohol intervention across different cultural settings and in specific population groups, and in respect of the optimum content of brief interventions that might benefit from further research.
PMCID: PMC3865817  PMID: 24232177
14.  Alcohol Screening and Brief Intervention for Adolescents: The How, What and Where of Reducing Alcohol Consumption and Related Harm Among Young People 
Aim: The aim of the study was to explore the evidence base on alcohol screening and brief intervention for adolescents to determine age appropriate screening tools, effective brief interventions and appropriate locations to undertake these activities. Methods: A review of existing reviews (2003–2013) and a systematic review of recent research not included in earlier reviews. Results: The CRAFFT and AUDIT tools are recommended for identification of ‘at risk’ adolescents. Motivational interventions delivered over one or more sessions and based in health care or educational settings are effective at reducing levels of consumption and alcohol-related harm. Conclusion: Further research to develop age appropriate screening tools needs to be undertaken. Screening and brief intervention activity should be undertaken in settings where young people are likely to present; further assessment at such venues as paediatric emergency departments, sexual health clinics and youth offending teams should be evaluated. The use of electronic (web/smart-phone based) screening and intervention shows promise and should also be the focus of future research.
PMCID: PMC3932830  PMID: 24232178
15.  Advanced Gestational Age Increases Serum Carbohydrate-Deficient Transferrin Levels in Abstinent Pregnant Women 
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.
PMCID: PMC3472616  PMID: 22878591
16.  What Research Is Being Done on Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorders in the Russian Research Community? 
Aims: Although Russia has one of the highest rates of alcohol consumption and alcohol-attributable burden of disease, little is known about the existing research on prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders (FASDs) in this country. The objective of this study was to locate and review published and unpublished studies related to any aspect of PAE and FASD conducted in or using study populations from Russia. Methods: A systematic literature search was conducted in multiple English and Russian electronic bibliographic databases. In addition, a manual search was conducted in several major libraries in Moscow. Results: The search revealed a small pool of existing research studies related to PAE and/or FASD in Russia (126: 22 in English and 104 in Russian). Existing epidemiological data indicate a high prevalence of PAE and FASD, which underlines the strong negative impact that alcohol has on mortality, morbidity and disability in Russia. High levels of alcohol consumption by women of childbearing age, low levels of contraception use, and low levels of knowledge by health and other professionals regarding the harmful effects of PAE put this country at great risk of further alcohol-affected pregnancies. Conclusions: Alcohol preventive measures in Russia warrant immediate attention. More research focused on alcohol prevention and policy is needed in order to reduce alcohol-related harm, especially in the field of FASD.
PMCID: PMC3865815  PMID: 24158024
17.  Social Inequalities and Gender Differences in the Experience of Alcohol-Related Problems 
Aims: To examine the influence of country-level characteristics and individual socio-economic status (SES) on individual alcohol-related consequences. Methods: Data from 42,655 men and women collected by cross-sectional surveys in 25 countries of the Gender, Alcohol and Culture: An International Study study were used. The individual SES was measured by the highest attained educational level. Alcohol-related consequences were defined as the self-report of at least one internal or one external consequence in the last year. The relationship between individuals’ education and alcohol-related consequences was examined by meta-analysis. In a second step, the individual level data and country data were combined in multilevel models. As country-level indicators, we used the purchasing power parity of the gross national income (GNI), the Gini coefficient and the Gender Gap Index. Results: Lower educated men and women were more likely to report consequences than higher educated men and women even after controlling for drinking patterns. For men, this relation was significant for both internal and external problems. For women, it was only significant for external problems. The GNI was significantly associated with reporting external consequences for men such that in lower income countries men were more likely to report social problems. Conclusion: The fact that problems accrue more quickly for lower educated persons even if they drink in the same manner can be linked to the social or environmental dimension surrounding problems. That is, those of fewer resources are less protected from the experience of a problem or the impact of a stressful life event.
PMCID: PMC3417684  PMID: 22542707
18.  Intermittent Availability of Ethanol Does Not Always Lead to Elevated Drinking in Mice 
Aims: Intermittent access (IA) to an alcohol (ethanol) solution can lead rats to higher ethanol intakes than continuous access, and a recent report showed increased drinking in C57BL/6J mice offered 20% ethanol vs. water 3X/week (Prior studies have offered ethanol during 24 h periods, either continuously or intermittently.). Methods: We tested the high-preference C57BL/6J inbred mice: we also studied High Drinking in the Dark (HDID) mice, a line we have selectively bred to reach intoxicating blood ethanol levels after a short period of access to a single bottle of 20% ethanol. Results: Neither HDID or C57BL/6J male mice offered ethanol every other day during only a 4-h access period showed greater daily intake than mice offered ethanol daily for 4 h. There was a small increase in drinking with 24 h IA in C57BL/6J mice. An experiment with HDID mice and their control heterogeneous stock stock modeled closely after a published study with C57BL/6J mice (Hwa, Chu, Levinson SA et al. Persistent escalation of alcohol drinking in C57BL/6J mice with intermittent access to 20% ethanol. Alcohol Clin Exp Res 2011;35:1938–1947) showed no significant elevation with 24 h IA exposure in either sex of any genotype. Finally, a near replication of the Hwa et al. study showed modestly greater intake in C57BL/6J mice, confirming the efficacy of 24 h IA. Conclusion: We conclude that 4 h of IA is likely insufficient to elevate drinking in mice. The lack of effect in HDID mice and their controls further suggests that not all genotypes respond to intermittency.
PMCID: PMC3417685  PMID: 22717273
19.  Acute Ethanol Does Not Always Affect Delay Discounting in Rats Selected to Prefer or Avoid Ethanol 
Aims: The purpose of this study was to determine whether animals predisposed to prefer alcohol possess an altered acute response to alcohol on a delay discounting task relative to animals predisposed to avoid alcohol. Methods: We used rats selected to prefer or avoid alcohol to assess whether genotype moderates changes in delay discounting induced by acute ethanol exposure. Selectively bred rat lines of Sardinian alcohol-preferring (sP; n = 8) and non-preferring (sNP; n = 8) rats, and alko alcohol (AA, n = 8) and alko non-alcohol (ANA, n = 8) rats were trained in an adjusting amount task to assess delay discounting. Results: There were no significant effects of line on baseline discounting; however, both lines of alcohol-preferring rats exhibit slowed reaction times. Acute ethanol (0, 0.25, 0.5 g/kg) treatment also had no effect on delay discounting in any of the selectively bred rat lines. Conclusion: Our data indicate that in these lines of animals, alcohol preference or avoidance has no impact on delay discounting following acute ethanol exposure. It is possible that other genetic models or lines may be differentially affected by alcohol and exhibit qualitatively and quantitatively different responses in delay discounting tasks.
PMCID: PMC3500854  PMID: 22645038
20.  Suicide Attempts During Heavy Drinking Episodes Among Individuals Entering Alcohol Treatment in Warsaw, Poland 
Aims: Acute alcohol intoxication itself may act as a trigger for suicidal thoughts and attempts among individuals at risk and may influence the potential lethality of the suicide attempt. This study in alcohol-dependent patients compared the correlates of suicide attempts during a heavy drinking episode with those of suicide attempts during relative sobriety. Methods: In two outpatient and two residential alcohol treatment programs in Warsaw, Poland, 113 patients who reported a suicide attempt during their lifetime were interviewed. The analyses focused on the patients’ most serious suicide attempts and on whether these occurred during a heavy drinking episode. Results: Over two-thirds of the patients reported that their most serious suicide attempt occurred during a period of heavy drinking. A multivariable logistic model indicated that the following factors significantly distinguished those patients whose most serious suicide attempt occurred during a heavy drinking episode: male gender, younger current age, greater severity of alcohol dependence and the attempt being unplanned. Conclusion: Among the patients in treatment for alcohol dependence who made a suicide attempt, the most serious attempt was likely to have been unplanned and committed by men when it occurred during a heavy drinking episode.
PMCID: PMC3500855  PMID: 22691386
21.  Efficacy of As-Needed Nalmefene in Alcohol-Dependent Patients with at Least a High Drinking Risk Level: Results from a Subgroup Analysis of Two Randomized Controlled 6-Month Studies 
Aims: The aim of the study was to investigate the efficacy and safety of as-needed use of nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment, i.e. the pooled subgroup of patients with at least a high drinking risk level (men: >60 g/day; women: >40 g/day) at both screening and randomization from the two randomized controlled 6-month studies ESENSE 1 (NCT00811720) and ESENSE 2 (NCT00812461). Methods: Nalmefene 18 mg and placebo were taken on an as-needed basis. All the patients also received a motivational and adherence-enhancing intervention (BRENDA). The co-primary outcomes were number of heavy drinking days (HDDs) and mean total alcohol consumption (g/day) in Month 6 measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study. Results: The pooled population consisted of 667 patients: placebo n = 332; nalmefene n = 335. There was a superior effect of nalmefene compared with placebo in reducing the number of HDDs [treatment difference: −3.2 days (95% CI: −4.8; −1.6); P < 0.0001] and total alcohol consumption [treatment difference: −14.3 g/day (−20.8; −7.8); P < 0.0001] at Month 6. Improvements in clinical status and liver parameters were greater in the nalmefene group compared with the placebo group. Adverse events and adverse events leading to dropout were more common with nalmefene than placebo. Conclusion: As-needed nalmefene was efficacious in reducing alcohol consumption in patients with at least a high drinking risk level at both screening and randomization, and the effect in this subgroup was larger than in the total population.
PMCID: PMC3746807  PMID: 23873853
22.  Longitudinal Prediction of Divorce in Russia: The Role of Individual and Couple Drinking Patterns 
Aims: The aim of the study was to explore associations between dimensions of alcohol use in married couples and subsequent divorce in Russia using longitudinal data. Methods: Follow-up data on 7157 married couples were extracted from 14 consecutive annual rounds (1994–2010) of the Russian Longitudinal Monitoring Survey, a national population-based panel study. Discrete-time hazard models were fitted to estimate the probability of divorce among married couples by drinking patterns reported in the previous survey wave. Results: In adjusted models, increased odds of divorce were associated with greater frequency of husband and wife drinking (test for trend P = 0.005, and P = 0.05, respectively), wife's binge drinking (P = 0.05) and husband's heavy vodka drinking (P = 0.005). Couples in whom the wife drank more frequently than the husband were more likely to divorce (OR 2.86, 95% CI 1.52–5.36), compared with other combinations of drinking. The association between drinking and divorce was stronger in regions outside Moscow or St. Petersburg. Conclusion: This study adds to the sparse literature on the topic and suggests that in Russia heavy and frequent drinking of both husbands and wives put couples at greater risk of future divorce, with some variation by region and aspect of alcohol use.
PMCID: PMC3799559  PMID: 23851365
23.  The Alcohol Improvement Programme: Evaluation of an Initiative to Address Alcohol-Related Health Harm in England 
Aims: The evaluation aimed to assess the impact of The Alcohol Improvement Programme (AIP). This was a UK Department of Health initiative (April 2008–March 2011) aiming to contribute to the reduction of alcohol-related harm as measured by a reduction in the rate of increase in alcohol-related hospital admissions (ARHAs). Methods: The evaluation (March 2010–September 2011) used a mix of qualitative and quantitative methods to assess the impact of the AIP on ARHAs, to describe and assess the process of implementation, and to identify elements of the programme which might serve as a ‘legacy’ for the future. Results: There was no evidence that the AIP had an impact on reducing the rise in the rate of ARHAs. The AIP was successfully delivered, increased the priority given to alcohol-related harm on local policy agendas and strengthened the infrastructure for the delivery of interventions. Conclusion: Although there was no measurable short-term impact on the rise in the rate of ARHAs, the AIP helped to set up a strategic response and a delivery infrastructure as a first, necessary step in working towards that goal. There are a number of valuable elements in the AIP which should be retained and repackaged to fit into new policy contexts.
PMCID: PMC3746805  PMID: 23729674
24.  Gene-Selective Histone H3 Acetylation in the Absence of Increase in Global Histone Acetylation in Liver of Rats Chronically Fed Alcohol 
Aims: The aim of this study was to determine the effect of chronic ethanol feeding on acetylation of histone H3 at lysine 9 (H3-Lys9) at promoter and coding regions of genes for class I alcohol dehydrogenase (ADH I), inducible nitric oxide synthase (iNOS), Bax, p21, c-met and hepatocyte growth factor in the rat liver. Methods: Rats were fed ethanol-containing liquid diet (5%, w/v) for 1–4 weeks. The global level of acetylation of H3-Lys9 in the liver was examined by western blot analysis. The levels of mRNA for various genes were measured by real-time reverse transcriptase-polymerase chain reaction. The association of acetylated histone H3-Lys9 with the different regions of genes was monitored by chromatin immunoprecipitation assay. Results: Chronic ethanol treatment increased mRNA expression of genes for iNOS, c-jun and ADH 1. Chronic ethanol treatment did not cause increase in global acetylation of H3-Lys9, but significantly increased the association of acetylated histone H3-Lys9 in the ADH I gene, both in promoter and in coding regions. In contrast, chronic ethanol treatment did not significantly increase the association of acetylated histone H3-Lys9 with iNOS and c-jun genes. Conclusion: Chronic ethanol exposure increased the gene-selective association of acetylated H3-Lys9 in the absence of global histone acetylation. Thus, not all genes expressed by ethanol are linked to transcription via histone H3 acetylation at Lys9.
PMCID: PMC3331618  PMID: 22301686
25.  Ethnic Drinking Cultures and Alcohol Use among Asian American Adults: Findings from a National Survey 
Aims: To investigate the influence of ethnic drinking cultures on alcohol use by Asian Americans and how this influence may be moderated by their level of integration into Asian ethnic cultures. Methods: A nationally representative sample of 952 Asian American adults extracted from the Wave 2 National Epidemiologic Survey of Alcohol and Related Conditions data was used. Multiple logistic and linear regression models were fitted, some of which were stratified by nativity. Results: Controlling for financial stress, discrimination and demographic variables, a hypothesized, positive relationship between ethnic drinking cultures and alcohol outcomes held for most drinking outcomes. A hypothesis on the moderating effect of integration into ethnic cultures indicated by ethnic language use was supported for US-born Asian Americans. Conclusion: Ethnic drinking cultures may significantly influence alcohol use by Asian Americans. The influence of ethnic drinking cultures may be conditioned by the degree of integration into the ethnic cultures. To inform alcohol interventions for reducing harmful and hazardous alcohol use among immigrants, future research needs to explore the cultural and social processes occurring in immigrant communities that might significantly influence drinking.
PMCID: PMC3331619  PMID: 22378829

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