To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.


Saturday, February 26, 2011

Bill W. Goes to Hollywood: The Rise and Fall of Recovering Addiction Experts

Although historians of addiction have long debated whether an oral culture of “sharing” or “Big Book”-based reading practices are foundational to 12-step recovery culture, the role other types of media have played in the development of contemporary recovery discourse has remained largely unexplored. 

This essay compares the production, reception and formal elements of the films The Lost Weekend and Smash Up in relation to the popularization of the disease concept of alcoholism. 

Through an analysis of archival sources, addiction narratives, and nascent alcoholism research, this paper argues that, by emphasizing the importance of popular representations of alcoholics above scientific inquiry, early recovering “experts” successfully promulgated the disease concept of alcoholism, but the testimonials of later recovering alcoholics became relegated to the sphere of popular culture. 

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Comparison of Healthcare Utilization Among Patients Treated With Alcoholism Medications

To determine in a large claims database the healthcare utilization and costs associated with treatment of alcohol dependence with medications vs no medication and across 4 US Food and Drug Administration (FDA)–approved medications.

Eligible adults with alcohol dependence claims (n = 27,135) were identified in a commercial database (MarketScan; Thomson Reuters Inc, Chicago, Illinois). 

Following propensity score–based matching and inverse probability weighting on demographic, clinical, and healthcare utilization variables, patients who had used an FDA-approved medication for alcohol dependence (n = 2977) were compared with patients who had not (n = 2977). Patients treated with oral naltrexone hydrochloride (n = 2064), oral disulfiram (n = 2076), oral acamprosate calcium (n = 5068), or extended release
injectable naltrexone (naltrexone XR) (n = 295) were also compared for 6-month utilization rates of alcoholism medication, inpatient detoxification days, alcoholism-related inpatient days, and outpatient services, as well as inpatient charges.

Patients who received alcoholism medications had fewer inpatient detoxification days (706 vs 1163 days per 1000 patients, P <.001), alcoholism-related inpatient days (650 vs 1086 days, P <.001), and alcoholism-related emergency
department visits (127 vs 171, P = .005). Among 4 medications, the use of naltrexone XR was associated with fewer inpatient detoxification days (224 days per 1000 patients) than the use of oral naltrexone (552 days, P = .001), disulfiram (403 days, P = .049), or acamprosate (525 days, P <.001). The group receiving naltrexone XR also had fewer alcoholism-related inpatient days than the groups receiving disulfiram or acamprosate. More patients in the naltrexone XR group had an outpatient substance abuse visit compared with patients in the oral alcoholism medication groups.

Patients who received an alcoholism medication had lower healthcare utilization than patients who did not. Naltrexone XR showed an advantage over oral medications in healthcare utilization and costs.

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Missing value imputation in longitudinal measures of alcohol consumption

Attrition in longitudinal studies can lead to biased results. 

The study is motivated by the unexpected observation that alcohol consumption decreased despite increased availability, which may be due to sample attrition of heavy drinkers. 

Several imputation methods have been proposed, but rarely compared in longitudinal studies of alcohol consumption. The imputation of consumption level measurements is computationally particularly challenging due to alcohol consumption being a semi-continuous variable (dichotomous drinking status and continuous volume among drinkers), and the non-normality of data in the continuous part. 

Data come from a longitudinal study in Denmark with four waves (2003–2006) and 1771 individuals at baseline. 

Five techniques for missing data are compared: Last value carried forward (LVCF) was used as a single, and Hotdeck, Heckman modelling, multivariate imputation by chained equations (MICE), and a Bayesian approach as multiple imputation methods. Predictive mean matching was used to account for non-normality, where instead of imputing regression estimates, “real” observed values from similar cases are imputed. Methods were also compared by means of a simulated dataset. 

The simulation showed that the Bayesian approach yielded the most unbiased estimates for imputation. The finding of no increase in consumption levels despite a higher availability remained unaltered.   

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Alcohol controls and violence in Nunavut: A comparison of wet and dry communities

A retrospective cross-sectional study based on community-level records of violent crimes known to the police.

Violence was measured using community-level records of homicide, assault and sexual assault as reported to the Royal Canadian Mounted Police in 23 communities in Nunavut for the years 1986 to 2006. Crude-rate comparisons were made between wet communities (which allow alcohol importation) and dry communities (which prohibit alcohol importation) and contrasted with national rates for context.

Wet communities in Nunavut recorded rates of violent crime that were higher than the rates recorded by dry communities. Relative to dry communities, wet communities’ overall sexual assault rate was 1.48 (95% CI=1.38–1.60) times higher, the serious assault rate was 2.10 (95% CI=1.88–2.35) times higher and the homicide rate was 2.88 (95% CI=1.18–8.84) times higher. Although safer than wet communities, dry communities reported rates of violence that were higher than national rates including a serious assault rate that was double the national rate (3.25 per 1,000 vs. 1.44 per 1,000) and a sexual assault rate that was at least seven times as high as the national rate (7.58 per 1,000 vs. 0.88 per 1,000).

As elsewhere in the Arctic, communities in Nunavut that prohibited alcohol were less violent than those that allowed alcohol importation. Even with prohibition, dry communities recorded rates of violence much greater than the national average.

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Predicting and Measuring Premises-Level Harm in the Night-Time Economy

To assess associations between measures of premises-level alcohol-related harm and risk factors for harm.
Thirty-two licensed premises with a history of on-premises violent assault were recruited. An environmental survey of the drinking context of each premises was undertaken. Levels of patron intoxication were assessed using a breathalyser and a visual assessment of customers at each premises. Premise-level violence was identified via routine police and hospital emergency department data. Analyses examined associations between hospital and police data, surveyor and objective ratings of intoxication and the relationship between intoxication, drinking context and violence at the premises level.
Hospital and police data were associated. Aggregate levels of surveyor-rated intoxication were associated with aggregate alcometer breath alcohol levels. Analyses further suggest that premises with the highest levels of violence also had customers whose entry–exit change in intoxication was greatest, were open for longer hours, had alcohol promotions and had visible security staff present.
Police and hospital data can be used to identify violent premises and to assess outcomes from premises-level interventions to reduce violence. Relatively low-cost observational survey methods can be used to identify high-risk premises, and can be used as outcomes for premises-level interventions. 

Features of premises that promote intoxication are associated with violence, suggesting that targeting resources at risky premises will likely address two public health concerns: excessive intoxication and assault-related injury. 

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Chronic Intermittent Ethanol Exposure in Early Adolescent and Adult Male Rats: Effects on Tolerance, Social Behavior, and Ethanol Intake

Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. 

The purpose of this study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood.

Juvenile/adolescent and adult male Sprague-Dawley rats were assigned to one of five 10-day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10), or nonmanipulated. For assessment of tolerance development, duration of the loss of righting reflex (LORR) and blood ethanol concentrations (BECs) upon regaining of righting reflex (RORR) were tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and nonmanipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hours after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and nonmanipulated animals using an 8-day 2 bottle choice, limited-access ethanol intake procedure.

In general, adolescent animals showed shorter durations of LORR and higher BECs upon RORR than adults on the first and last ethanol exposure days, regardless of chronic exposure condition. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults. Adolescents drank significantly more ethanol than adults on a gram per kilogram basis, with intake uninfluenced by prior ethanol exposure at both ages.

Adolescents and adults may differ in their ability and/or propensity to adapt to chronic ethanol exposure, with adults, but not adolescents, developing chronic metabolic tolerance. However, this chronic exposure regimen was sufficient to disrupt baseline levels of social behavior at both ages. Taken together, these results suggest that, despite the age-related differences in tolerance development, adolescents are as susceptible as adults to consequences of chronic ethanol exposure, particularly in terms of disruptions in social behavior. Whether these effects would last into adulthood remains to be determined.

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Threshold and Optimal Cut-Points for Alcohol Use Disorders Among Patients in the Emergency Department

Current research suggests that Diagnostic and Statistical Manual of Mental Disorder (DSM)-IV alcohol abuse and dependence form a unidimensional continuum in emergency department (ED) patients in 4 countries: Argentina, Mexico, Poland, and the United States. In this continuum of alcohol use disorder (AUD), there are no clear-cut distinctions between the criteria for dependence and abuse in the severity dimension based on prior results from item response theory (IRT) analysis. Nevertheless, it is desirable to find a threshold for identifying cases for clinical practice and cut-points of clinical utility in this continuum to distinguish between patients more or less affected by an AUD, using a scale of symptoms count.

Data from 5,193 patients in 7 ED sites in the same 4 countries (3,191 current drinkers) were used to study the structure, threshold, and possible cut-points for the diagnoses of AUD.

The proposed changes in the DSM-V, dropping the abuse item “legal problems” and adding an item on “craving,” did not impact the IRT performance and unidimensionality of AUD in this sample. With a total set of 11 items (deleting “legal problems” and adding “craving” to the current set of DSM criteria), an endorsement of 2 or more criteria can be used as the threshold to define those with an AUD in clinical practice. Furthermore, we can distinguish at least 2 levels of clinical severity, 2 to 3 criteria (moderate), and 4 or more criteria (severe).

A dimensional approach to AUD using the proposed new set of criteria for the DSM-V can be used to propose a threshold and levels of severity. More research in different populations and countries is needed to further substantiate a threshold and cut-points that could be used in new formulations of substance use disorders.

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Dose-Related Influence of Chronic Alcohol Consumption on Cerebral Ischemia/Reperfusion Injury

We examined the dose-related influence of alcohol consumption on cerebral ischemia/reperfusion (I/R) injury and the potential mechanism that accounts for the disparate effects of high-dose and low-dose alcohol consumption on cerebral I/R injury.

Sprague–Dawley rats were fed a liquid diet with or without 1, 3, 5, or 6.4% (v/v) alcohol for 8 weeks and subjected to a 2-hour middle cerebral artery occlusion (MCAO). We evaluated the brain injury at 24 hours of reperfusion. In addition, we measured protein expression of NMDA receptor and excitatory amino acid transporters (EAATs) in parietal cortex and the effect of NMDA receptor antagonist, memantine, on 2-hour MCAO/24 h reperfusion-induced brain injury.

Compared with non–alcohol-fed rats, the total infarct volume was not altered in 3 and 5% alcohol-fed rats but significantly reduced in 1% alcohol-fed rats and exacerbated in 6.4% alcohol-fed rats. Expression of the NMDA receptor subunit, NR1, was upregulated in 6.4% alcohol-fed rats, whereas expression of EAAT2 was downregulated in 6.4% alcohol-fed rats and upregulated in 1% alcohol-fed rats. Memantine reduced 2-hour MCAO/24 h reperfusion-induced brain injury in non–alcohol-fed and 6.4% alcohol-fed rats, but not in 1% alcohol-fed rats. The magnitude of reduction in the brain injury was greater in 6.4% alcohol-fed rats compared to non–alcohol-fed rats.

Our findings suggest that chronic consumption of low-dose alcohol protects the brain against I/R injury, whereas chronic consumption of high-dose alcohol has detrimental effect on cerebral I/R injury. The disparate effects of low-dose and high-dose alcohol consumption on cerebral I/R may be related to an alteration in NMDA excitotoxicity.

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Ethanol as a Prodrug: Brain Metabolism of Ethanol Mediates Its Reinforcing Effects – A Commentary

This commentary discusses a study by Karahanian and colleagues (2011) on the role of central nervous system acetaldehyde in the reinforcing effects of ethanol. The goal is to emphasize the importance of the study and to discuss future directions.

This important paper solidifies the idea that the levels of acetaldehyde in the central nervous system have profound effects in mediating the reinforcing actions of ethanol. This is accomplished by manipulating the brain levels of acetaldehyde produced from ethanol by the injection of lentivirus containing either an anti-catalase shRNA construct or a rat liver alcohol dehydrogenase into the central nervous system and observing the effects on alcohol preference by high ethanol-consuming rats. A factor not directly considered is that acetaldehyde is further metabolized to acetate, which also has some behavioral actions.

The efficacy of lentivirus injections of enzyme inhibitors or enzymes themselves to alter a behavioral response to ethanol is clearly demonstrated here. The many other actions of ethanol that are postulated to be a result of the production of acetaldehyde in the brain remain to be investigated by similar techniques. Possible “therapeutic avenues to reduce chronic alcohol use” are envisioned.

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Polymorphism of N-acetyltransferase 2 Gene and the Susceptibility to Alcoholic Liver Cirrhosis: Interaction With Smoking

Polymorphism of N-acetyltransferase 2 gene was reported to be associated with the susceptibility of various cancers and liver diseases. However, its relationship to alcoholic liver disease is controversial and open to debate. 

The aim of this study was to evaluate the relationship of NAT2 genetic polymorphisms and the susceptibility to alcoholic liver cirrhosis (ALC) in Chinese, with special emphasis on the interaction of smoking.

Peripheral white blood cell DNA from 148 patients with ALC, 104 patients with long-term alcoholic drinking but without cirrhosis (ANC) and 209 healthy controls were genotyped for NAT2 using a polymerase chain reaction–restriction fragment length polymorphism method. The possible confounding factors were included for analysis.

There was no statistical difference in the frequency of NAT2 genotype or NAT2 acetylator status among the 3 groups. However, among the chronic alcoholic drinkers, the rapid acetylators with smoking habits had higher percentage of ALC than those without smoking habit (18.9% vs. 9.5%, p = 0.002). The adjusted odds ratio for rapid acetylator smoker to have ALC was 3.45 (95% CI = 1.53 to 7.76, p = 0.003).

The genetic factor, NAT2 polymorphism, may interact with environmental factor, smoking, to confer different susceptibilities to ALC. NAT2 rapid acetylators with smoking habit may increase the risk of ALC in Chinese.

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Friday, February 25, 2011

Long-Term Mortality of Patients Admitted to the Hospital With Alcohol Withdrawal Syndrome

Although it is well known that alcoholism increases long-term mortality, there is a paucity of data regarding long-term prognosis in alcoholic patients who have an episode of alcohol withdrawal syndrome (AWS).

We studied a cohort of 1,265 individuals with severe AWS who were admitted to a single university hospital between 1996 and 2006. Median age was 49 years (range 18 to 89 years). A total of 1,085 (85.8%) were men. Median follow-up was 34 months (range 0 to 121 months). Survival of patients with AWS was compared with that of a reference cohort of 1,362 individuals from the same area. In addition, age- and sex-standardized mortality ratios were calculated using the general population from the region (Galicia, Spain) as the reference.

The risk of mortality was higher in the cohort of patients with AWS than in the reference cohort after adjusting for age, sex, and smoking (hazard ratio 12.7; 95% CI 9.1 to 17.6; < 0.001). The standardized mortality ratio in patients with AWS was 8.6 (95% CI 7.7 to 9.7). Age, smoking, serum creatinine, serum bilirubin, and prothrombin time at baseline were independently associated with mortality among patients with AWS.

Long-term mortality is highly increased in patients who have a history of AWS. Liver and kidney dysfunction are independent predictors of long-term mortality in patients with AWS.

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Event-Related Potentials During Visual Target Detection in Treatment-Naïve Active Alcoholics

Reduced P3b event-related potentials (ERP) amplitude during visual target detection in alcoholics is a robust phenomenon. However, this finding is based primarily on samples of treated alcoholics, who comprise only about 25% of alcoholics. 

We studied visual target detection in a treatment-naïve alcohol-dependent sample (TNAD) versus age and gender comparable nonalcoholic controls (NAC) to investigate whether reduced P3 amplitudes generalize to TNAD.

EEGs were recorded from 74 TNAD and 63 age and gender comparable NAC during visual target detection. ANOVA was applied at midline electrodes to amplitudes and latencies of N2 and P3 ERP components during target and rare nontarget conditions.

Treatment-naïve alcohol-dependent subjects had a modestly lower P3b amplitude (p = 0.05) and a more robustly lower N2b amplitude (p = 0.29). In the target condition, TNAD showed a significant reduction in P3b amplitude and a larger reduction in N2b amplitude, with these phenomena being independent of each other. Latencies to P3b, N2b, and P3a were earlier in TNAD than NAC, with this effect correlating with our reported effect of better attention in TNAD versus NAC.

The significant reduction in P3b amplitude in TNAD suggests that this phenomenon is present in TNAD, but dramatically smaller than that observed in treated samples (we reported an effect over 5 times as large in treated long-term abstinent alcoholics). The N2b amplitude reduction (not present in long-term abstinent alcoholics) may reflect the effects of active alcohol abuse. Finally, the shorter latencies of these components in TNAD is associated with better scores on tests of attention and may reflect compensatory attentional effort in the context of active drinking.

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Effects of Dose and Period of Neonatal Alcohol Exposure on the Context Preexposure Facilitation Effect

Alcohol exposure in the rat on postnatal days (PD) 4 to 9 is known to partially damage the hippocampus and to impair hippocampus-dependent behavioral tasks. We previously reported that PD4 to 9 alcohol exposure eliminated the context preexposure facilitation effect (CPFE) in juvenile rats, a hippocampus-dependent variant of contextual fear conditioning. In the CPFE, context exposure and immediate shock occur on successive occasions and this produces conditioned freezing relative to a control group that is not preexposed to the training context. 

Here, we extend our earlier findings by examining the effects of neonatal alcohol administered at multiple doses or over different neonatal exposure periods.

Rat pups (male and female) were exposed to a single binge dose of alcohol at one of 3 doses (2.75, 4.00, or 5.25 g/kg/d) over PD4 to 9 (Experiment 1) or to 5.25 g over PD4 to 6 or PD7 to 9 (Experiment 2). Sham-intubated (SI) and undisturbed (UD) rats served as controls. On PD31, rats were preexposed to either the training context (Pre) or an alternate context (No-Pre). On PD32, rats received an immediate unsignaled footshock (1.5 mA, 2 seconds) in the training context. Finally, on PD33, all rats were returned to the training context and tested for contextual freezing over a 5-minute period.

Undisturbed- and SI-Pre rats showed the CPFE, i.e., context preexposure facilitated contextual conditioning, relative to their No-Pre counterparts. The immediate shock deficit was present in all No-Pre groups, regardless of previous alcohol exposure. In Experiment 1, blood alcohol level was negatively correlated with contextual freezing. Group 2.75 g-Pre did not differ from controls. Group 4.00 g-Pre froze significantly less than Groups UD- and SI-Pre but more than Group 5.25-Pre, which showed the immediate shock deficit. In Experiment 2, alcohol exposure limited to PD7 to 9, but not PD4 to 6, disrupted the CPFE.

This is the first demonstration of dose-related impairment on a hippocampus-dependent task produced by neonatal alcohol exposure in the rat. Exposure period effects support previous studies of alcohol and spatial learning. The CPFE is a more sensitive behavioral task that can be used to elucidate developmental alcohol-induced deficits over a range of alcohol doses that are more relevant to human exposure levels.

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Effect of the Selective NMDA NR2B Antagonist, Ifenprodil, on Acute Tolerance to Ethanol-Induced Motor Impairment in Adolescent and Adult Rats

Adolescent rats have been observed to be less sensitive than adults to a number of acute ethanol effects, including ethanol-induced motor impairment. These adolescent insensitivities may be related in part to the more rapid emergence of within session (acute) tolerance in adolescents than adults. Adolescent-related alterations in neural systems that serve as ethanol target sites, including changes in NMDA receptor subunit expression, may influence the responsiveness of adolescents to acute ethanol effects. 

This study explored the role of NMDA NR2B receptors in the development of acute tolerance to ethanol-induced motor impairment in male adolescent [postnatal day (P)28–30] and adult (P68–70) Sprague–Dawley rats.

Motor-impairing effects of ethanol on the stationary inclined plane and blood ethanol concentrations (BECs) were examined following challenge at each age with a functionally equivalent ethanol dose (adolescents: 2.25 g/kg; adults: 1.5 g/kg). Data were collected at two postinjection intervals (10 or 60 minutes) to compare rate of recovery from ethanol intoxication with BEC declines using the Radlow approach (Radlow, 1994) and changes in motor impairment/BEC ratios over time for assessing acute tolerance.

Both vehicle-treated adolescent and adult animals showed similar acute tolerance development to the motor-impairing effects of ethanol at these functionally equivalent doses on the stationary inclined plane, as indexed by an increasing time-dependent dissociation between BECs and ethanol-induced motor impairment, with motor impairment declining faster than BECs, as well as by significant declines in motor impairment/BEC ratios over time. Acute tolerance development was reliably blocked by administration of the NR2B antagonist, ifenprodil, (5.0 mg/kg), in adult rats, whereas adolescents were affected by a higher dose (10.0 mg/kg).

These data support the suggestion that alterations in NMDA receptor systems occurring during adolescence may contribute to reduced sensitivity to ethanol by enhancing the expression of acute tolerance development in adolescents relative to adults.

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Public health importance of triggers of myocardial infarction: a comparative risk assessment

Acute myocardial infarction is triggered by various factors, such as physical exertion, stressful events, heavy meals, or increases in air pollution. However, the importance and relevance of each trigger are uncertain. We compared triggers of myocardial infarction at an individual and population level.
We searched PubMed and the Web of Science citation databases to identify studies of triggers of non-fatal myocardial infarction to calculate population attributable fractions (PAF). When feasible, we did a meta-regression analysis for studies of the same trigger.
Of the epidemiologic studies reviewed, 36 provided sufficient details to be considered. In the studied populations, the exposure prevalence for triggers in the relevant control time window ranged from 0·04% for cocaine use to 100% for air pollution. The reported odds ratios (OR) ranged from 1·05 to 23·7. Ranking triggers from the highest to the lowest OR resulted in the following order: use of cocaine, heavy meal, smoking of marijuana, negative emotions, physical exertion, positive emotions, anger, sexual activity, traffic exposure, respiratory infections, coffee consumption, air pollution (based on a difference of 30 μg/m3 in particulate matter with a diameter <10 μm [PM10]). Taking into account the OR and the prevalences of exposure, the highest PAF was estimated for traffic exposure (7·4%), followed by physical exertion (6·2%), alcohol (5·0%), coffee (5·0%), a difference of 30 μg/m3 in PM10 (4·8%), negative emotions (3·9%), anger (3·1%), heavy meal (2·7%), positive emotions (2·4%), sexual activity (2·2%), cocaine use (0·9%), marijuana smoking (0·8%) and respiratory infections (0·6%).
In view of both the magnitude of the risk and the prevalence in the population, air pollution is an important trigger of myocardial infarction, it is of similar magnitude (PAF 5—7%) as other well accepted triggers such as physical exertion, alcohol, and coffee. Our work shows that ever-present small risks might have considerable public health relevance.
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Specialist Drug and Alcohol Services for Young People – A cost benefit analysis

This report looks at the costs and benefits associated with young people’s drug and alcohol treatment.

There were approximately 24,000 young people who received specialist drug and alcohol treatment in the UK in 2008-09. This is defined as “a care planned medical, psychosocial or specialist harm reduction intervention”. As set out in the Drug Strategy 2010 such treatment is aimed at preventing escalation of use or harm and should “respond incrementally to the risks in terms of drug use,
vulnerability and, particularly, age.” Most of these young people were treated primarily for alcohol (37%) or cannabis (53%) misuse, with the remaining 10% misusing Class A drugs, including heroin and crack. Apart from using drugs and alcohol, these young people had experienced a range of other problems, including involvement in crime (shoplifting, theft, assault); being NEET (not in education, employment or training); or housing problems.

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Alcohol Use as a Marker for Risky Sexual Behaviors and Biologically Confirmed Sexually Transmitted Infections Among Young Adult African-American Women

Previous research has primarily focused on the relationship between illicit drug use and HIV/sexually transmitted infection (STI) risk behavior among African-American women. Very few studies have solely reviewed the role of alcohol use on risky sexual behavior. 

The present study examined the relationship between alcohol use at non-abuse levels and risky sexual behaviors and STIs among young adult African-American women.

Eight hundred forty-eight African American women, ages 18 to 29, participated at baseline, with 669 and 673 women at 6 and 12 months follow-up, respectively. Participants completed an Audio Computer Assisted Survey Interview assessing sociodemographics, alcohol use, and risky sexual behaviors. Subsequently, participants provided two vaginal swab specimens for STIs.

Multivariate logistic regression analyses were conducted for cross-sectional analyses, with illicit drug use as a covariate. Women who consumed alcohol were more likely to have multiple partners and risky partners. Binary generalized estimating equation models assessed the impact of alcohol use at baseline on risky sexual behavior and STIs over a 12-month period. Illicit drug use, intervention group, and baseline outcome measures were entered as covariates. 

Alcohol consumption predicted positive results for chlamydia, positive results for any STI, and never using a condom with a casual partner over a 12-month follow-up period.
Frequency of alcohol use at non-abuse levels was correlated with and predicted risky sexual behaviors and STIs. Prevention programs for African-American women should incorporate education regarding the link between alcohol and HIV/STI risk behaviors and the potential negative health consequences.

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Thursday, February 24, 2011

Alteration of gene expression by alcohol exposure at early neurulation

We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. 

To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. 

Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. 

In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. 

There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). 

Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. 

The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. 

Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). 

Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic / growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos.

This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube defects during early neurulation. 

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Acetate-Dependent Mechanisms of Inborn Tolerance to Ethanol

To clarify the role of acetate in neurochemical mechanisms of the initial (inborn) tolerance to ethanol. 

Rats with low and high inborn tolerance to hypnotic effect of ethanol were used. In the brain region homogenates (frontal and parietal cortex, hypothalamus, striatum, medulla oblongata) and brain cortex synaptosomes, the levels of acetate, acetyl-CoA, acetylcholine (AcH), the activity of pyruvate dehydrogenase (PDG) and acetyl-CoA synthetase were examined.  

It has been found that brain cortex of rats with high tolerance to hypnotic effect of ethanol have higher level of acetate and activity of acetyl-CoA synthetase, but lower level of acetyl-СCoA and activity of PDG. In brain cortex synaptosomes of tolerant rats, the pyruvate oxidation rate as well as the content of acetyl-CoA and AcH synthesis were lower when compared with intolerant animals. The addition of acetate into the medium significantly increased the AcH synthesis in synaptosomes of tolerant, but not of intolerant animals. Calcium ions stimulated the AcH release from synaptosomes twice as high in tolerant as in intolerant animals. Acetate eliminated the stimulating effect of calcium ions upon the release of AcH in synaptosomes of intolerant rats, but not in tolerant animals. As a result, the quantum release of AcH from synaptosomes in the presence of acetate was 6.5 times higher in tolerant when compared with intolerant rats. 

The brain cortex of rats with high inborn tolerance to hypnotic effect of ethanol can better utilize acetate for the acetyl-CoA and AcH synthesis, as well as being resistant to inhibitory effect of acetate to calcium-stimulated release of AcH. It indicates the metabolic and cholinergic mechanisms of the initial tolerance to ethanol. 

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Mayor's report proposes 'alcohol sobriety scheme' for London

Members of the Metropolitan Police Authority (MPA) have received a report from the Mayor on the proposal of a alcohol sobriety scheme for London:
'The compulsory alcohol sobriety scheme is an enforcement approach providing specific powers for the court to order sobriety as an order for alcohol related violence offences. The Mayor is tabling an amendment to the Police Reform and Social Responsibility Bill for changes in the current law to enable the courts to make this order. The compulsory alcohol requirement will involve twice daily testing and failure of the test will result in immediate breach and sanctions, such as custody.'
'It is based around some key principles:
  • The judges opt to use compulsory sobriety as a sentencing option instead of choosing to incarcerate offenders.
  • The convicted individual is required to check into a designated venue twice daily to be breathalysed for alcohol consumption.
  • If the terms of the sentence are breached, the individual is arrested, put into a police cell over night and presented to the judge the following day. The judge has the discretion to decide what happens to the offender, for example incarcerate them, put them back on community sentence etc.
  • Individuals pay for their testing.'    > > > >  Read More

News Release - Liquor outlet density and assault

Only 3 per cent of the Sydney LGA is within 20 metres of a liquor outlet, yet 37 per cent of assaults in Sydney LGA occur within 20 metres of a liquor outlet.

More than half of the assaults recorded by police in the Sydney CBD occur within 50 metres of a liquor outlet.

Each additional alcohol outlet per hectare in the Sydney LGA will result, on average, in 4.5 additional assaults per annum.

These are the key findings to emerge from a study of assaults in and around licensed premises in the Sydney Local Government Area (LGA).  > > > >  Read More

The association between alcohol outlet density and assaults on and around licensed premises

To estimate the proportion of assaults occurring on or around licensed premises, determine whether assaults are more likely to happen around licensed premises than elsewhere and estimate the effect of additional alcohol outlets (outlet density) on the incidence of assault.

Clusters of licensed premises in the Sydney Local Government Area (LGA) were identified. The proportion of
recorded assault incidents within 20, 50, 100 and 200 metre buffer zones around the licensed premises was calculated
and compared with the proportion of land area covered by the buffer. The incidence of recorded assaults as a function of
increasing counts of alcohol outlets was also examined.

Assaults were found to be highly concentrated around licensed premises. Assaults tend to cluster around George Street in the central business district (CBD), Darlinghurst Road in Kings Cross, Oxford Street in Darlinghurst, King Street in Newtown and Glebe Point Road in Glebe. The highest concentrations of assault are in Kings Cross, Oxford Street in Darlinghurst and along George Street in the CBD. More than half of the assaults recorded by police in the Sydney CBD occur within 50 metres of a liquor outlet. Only 3 per cent of the Sydney LGA is within 20 metres of a liquor outlet, yet 37 per cent of assaults in Sydney LGA occurred in this space.

The results suggest that each additional alcohol outlet per hectare in the Sydney LGA will result, on average, in 4.5 additional assaults per annum.

Limiting the density of alcohol outlets may help limit the incidence of assault.
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Outlet Density as a Predictor of Alcohol Use in Early Adolescence

Recent national youth surveys suggest that alcohol availability plays a role in determining use. One measure of availability receiving recent attention is outlet density; however, few studies have examined the effects of outlet density in younger populations. Methods: Data were collected from a national sample of the United States (N = 5,903) followed between 6th and 8th grades, as part of a study funded by the Office of Juvenile Justice and Delinquency Prevention (OJJDP). Measures of outlet density were also acquired. Results: Students in high off-site density communities increased their alcohol use; however, students attending schools in low outlet density communities had higher initial levels of alcohol use that remained relatively stable. Discussion: The implications and limitations of these findings are discussed.

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Recent national youth surveys suggest that alcohol availability plays a role in determining use. One measure of availability receiving recent attention is outlet density; however, few studies have examined the effects of outlet density in younger populations. Methods: Data were collected from a national sample of the United States (N = 5,903) followed between 6th and 8th grades, as part of a study funded by the Office of Juvenile Justice and Delinquency Prevention (OJJDP). Measures of outlet density were also acquired. Results: Students in high off-site density communities increased their alcohol use; however, students attending schools in low outlet density communities had higher initial levels of alcohol use that remained relatively stable. Discussion: The implications and limitations of these findings are discussed.

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Recent national youth surveys suggest that alcohol availability plays a role in determining use. One measure of availability receiving recent attention is outlet density; however, few studies have examined the effects of outlet density in younger populations.

Data were collected from a national sample of the United States (N = 5,903) followed between 6th and 8th grades, as part of a study funded by the Office of Juvenile Justice and Delinquency Prevention (OJJDP). Measures of outlet density were also acquired.

Students in high off-site density communities increased their alcohol use; however, students attending schools in low outlet density communities had higher initial levels of alcohol use that remained relatively stable.

The implications and limitations of these findings are discussed.

Recent national youth surveys suggest that alcohol availability plays a role in determining use. One measure of availability receiving recent attention is outlet density; however, few studies have examined the effects of outlet density in younger populations. Methods: Data were collected from a national sample of the United States (N = 5,903) followed between 6th and 8th grades, as part of a study funded by the Office of Juvenile Justice and Delinquency Prevention (OJJDP). Measures of outlet density were also acquired. Results: Students in high off-site density communities increased their alcohol use; however, students attending schools in low outlet density communities had higher initial levels of alcohol use that remained relatively stable. Discussion: The implications and limitations of these findings are discussed.

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The Cognitive Underpinnings of Addiction

A new conditional reasoning measure was developed to evaluate the role of implicit biases in perpetuating addictive behavior. Data (N = 669) were collected in 2005 from two samples in a suburban area: individuals with a known history of chemical dependency and individuals from the general population.

Results indicated a strong correlation between overall test scores and group membership (rpb = .48), which increased when the groups’ demographic characteristics were equalized (rpb = .65).

Overall, findings suggest that addiction-prone individuals rely on a distinct set of cognitive biases that rationalize self-destructive behavior.

The study's limitations are noted and implications and directions for future research are discussed.

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National Coverage Analysis (NCA) for Screening and Behavioral Counseling Interventions in Primary Care to Reduce Alcohol Misuse (CAG-00427N)

Over the past 25 years, the Congress has expanded the Medicare benefit to include various preventive services to the Medicare Part B program such as Pap smear and screening pelvic exams, screening mammograms, colorectal cancer screening tests, and diabetes screening tests. Effective January 1, 2009, CMS is allowed to add coverage of "additional preventive services" if certain statutory requirements are met, as provided under section 101(a) of the Medicare Improvements for Patients and Providers Act of 2008 (MIPPA) (Pub. L. 110-275). Among other things, this new benefit allows CMS under 42 CFR 410.64 to cover "additional preventive services", if it determines through the NCD process that the service is recommended with a grade A (strongly recommends) or grade B (recommends) rating by the United States Preventive Services Task Force (USPSTF) and meets certain other requirements.

After reviewing various preventive services given a grade A or grade B recommendation by the USPSTF, CMS has decided to initiate a new national coverage analysis (NCA) on Screening and Behavioral Counseling Interventions in Primary Care to Reduce Alcohol Misuse, which is recommended with a grade B by the USPSTF. We would be interested in receiving any recommendations on the appropriate frequency of this service and those qualified to provide it based on documentation from the medical literature, current clinical practice guidelines, or the USPSTF recommendations.

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Socioeconomic Status, Psychological Distress, and Other Maternal Risk Factors for Fetal Alcohol Spectrum Disorders among American Indians of the Northern Plains

The relationship of selected demographic, socioeconomic status (SES), and psychological characteristics was examined in interviews with 176 Northern Plains American Indian mothers whose children were referred to diagnostic clinics for evaluation of developmental disabilities, including fetal alcohol spectrum disorders (FASD). 

Thirty-nine mothers had children diagnosed with an FASD (Group 1), 107 had children who were not diagnosed with an FASD or other major disability (Group 2), and 30 additional mothers with normally performing children, matched by age, sex, and reservation with those diagnosed with an FASD, were recruited as a comparison group (Group 3). 

Analysis revealed statistically signifi cant differences (p < .001) in alcohol consumption among all three groups, and a statistically signifi cant difference in the mean Total Distress score among the three groups of mothers, F(2, 176) = 9.60, p < .001, with Group 3 having a lower mean score than Groups 1 and 2. 

Sequential regression analysis revealed that the quantity of alcohol consumed prior to knowledge of pregnancy, when combined with SES and Total Distress, was more highly associated with having a child diagnosed with an FASD (R2 = .206) than was quantity of alcohol consumed alone.

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The effect of age on the discriminative stimulus effects of ethanol and its GABAA receptor mediation in cynomolgus monkeys

Excessive alcohol consumption is less common among aged compared to young adults, with aged adults showing greater sensitivity to many behavioral effects of ethanol.

This study compared the discriminative stimulus effects of ethanol in young and middle-aged adult cynomolgus monkeys (Macaca fascicularis) and its γ-aminobutyric acid (GABA)A receptor mediation.
Two male and two female monkeys trained to discriminate ethanol (1.0 g/kg, i.g.; 60-min pre-treatment interval) from water at 5–6 years of age (Grant et al. in Psychopharmacology 152:181–188, 2000) were re-trained in the current study more than a decade later (19.3 ± 1.0 years of age) for a within-subjects comparison. Also, four experimentally naïve middle-aged (mean ± SEM, 17.0 ± 1.5 years of age) female monkeys were trained to discriminate ethanol for between-subjects comparison with published data from young adult naïve monkeys.
Two of the naïve middle-aged monkeys attained criterion performance, with weak stimulus control and few discrimination tests, despite greater blood–ethanol concentration 60 min after 1.0 g/kg ethanol in middle-aged compared to young adult female monkeys (Green et al. in Alcohol Clin Exp Res 23:611–616, 1999). The efficacy of the GABAA receptor positive modulators pentobarbital, midazolam, allopregnanolone, pregnanolone, and androsterone to substitute for the discriminative stimulus effects of 1.0 g/kg ethanol was maintained from young adulthood to middle age.
The data suggest that 1.0 g/kg ethanol is a weak discriminative stimulus in naive middle-aged monkeys. Nevertheless, the GABAA receptor mechanisms mediating the discriminative stimulus effects of ethanol, when learned as a young adult, appear stable across one third of the primate lifespan. 
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Wednesday, February 23, 2011

κ-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats

Previously, it was shown that ethanol dependent animals display increased sensitivity to the general opioid receptor antagonist nalmefene compared to naltrexone. 

It was hypothesized that the dissociable effects of the two antagonists was attributable to a κ-opioid receptor mechanism. Nucleus accumbens dynorphin is upregulated following chronic ethanol exposure and such neuroadaptations could contribute to nalmefene's increased potency in ethanol-dependent animals. 

To test this hypothesis, male Wistar rats were trained to self-administer ethanol using an operant conditioning procedure. Animals were then implanted with bilateral intra-accumbens shell guide cannulae and assigned to either a chronic intermittent ethanol vapor exposure condition (to induce dependence) or an air-exposed control group. Following a one-month exposure period, nalmefene, nor-binaltorphimine (nor-BNI; selective for κ-opioid receptors) or a combination of the selective opioid receptor antagonists CTOP and naltrindole (selective for the μ- and δ-opioid receptors, respectively) were site-specifically infused into the nucleus accumbens shell prior to ethanol self-administration sessions during acute withdrawal. 

Nalmefene and CTOP / naltrindole dose-dependently reduced ethanol self-administration in nondependent and dependent animals, whereas nor-BNI selectively attenuated ethanol self-administration in ethanol-dependent animals without affecting the self-administration of nondependent animals. 

Further analysis indentified that intra-accumbens shell nalmefene was more potent in ethanol dependent animals and that the increased potency was attributable to a κ-opioid receptor mechanism. 

These data support the concept that dysregulation of DYN / κ-opioid receptor systems contributes to the excessive self-administration observed in dependent animals and suggest that pharmacotherapeutics for ethanol dependence that target κ-opioid receptors, in addition to μ- and δ-opioid receptors, are preferable than those that target μ- and δ-opioid receptor mechanisms alone.

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Health Behaviours, Socioeconomic Status, and Mortality: Further Analyses of the British Whitehall II and the French GAZEL Prospective Cohorts Further analysis of data from two prospective cohorts reveals differences in the extent to which health behaviors attenuate associations between socioeconomic position and mortality outcomes.

Differences in morbidity and mortality between socioeconomic groups constitute one of the most consistent findings of epidemiologic research. However, research on social inequalities in health has yet to provide a comprehensive understanding of the mechanisms underlying this association. In recent analysis, we showed health behaviours, assessed longitudinally over the follow-up, to explain a major proportion of the association of socioeconomic status (SES) with mortality in the British Whitehall II study. However, whether health behaviours are equally important mediators of the SES-mortality association in different cultural settings remains unknown. 

In the present paper, we examine this issue in Whitehall II and another prospective European cohort, the French GAZEL study.

We included 9,771 participants from the Whitehall II study and 17,760 from the GAZEL study. Over the follow-up (mean 19.5 y in Whitehall II and 16.5 y in GAZEL), health behaviours (smoking, alcohol consumption, diet, and physical activity), were assessed longitudinally. Occupation (in the main analysis), education, and income (supplementary analysis) were the markers of SES. 

The socioeconomic gradient in smoking was greater (p<0.001) in Whitehall II (odds ratio [OR] = 3.68, 95% confidence interval [CI] 3.11–4.36) than in GAZEL (OR = 1.33, 95% CI 1.18–1.49); this was also true for unhealthy diet (OR = 7.42, 95% CI 5.19–10.60 in Whitehall II and OR = 1.31, 95% CI 1.15–1.49 in GAZEL, p<0.001). 

Socioeconomic differences in mortality were similar in the two cohorts, a hazard ratio of 1.62 (95% CI 1.28–2.05) in Whitehall II and 1.94 in GAZEL (95% CI 1.58–2.39) for lowest versus highest occupational position. 

Health behaviours attenuated the association of SES with mortality by 75% (95% CI 44%–149%) in Whitehall II but only by 19% (95% CI 13%–29%) in GAZEL. Analysis using education and income yielded similar results.

Health behaviours were strong predictors of mortality in both cohorts but their association with SES was remarkably different. Thus, health behaviours are likely to be major contributors of socioeconomic differences in health only in contexts with a marked social characterisation of health behaviours.

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