Alcohol-attributable injuries in admissions to a swiss emergency room--an analysis of the link between volume of drinking, drinking patterns, and preattendance drinking.

BACKGROUND: An association between alcohol consumption and injury is clearly established from volume of drinking, heavy episodic drinking (HED), and consumption before injury. Little is known, however, about how their interaction raises risk of injury and what combination of factors carries the highest risk. This study explores which of 11 specified groups of drinkers (a) are at high risk and (b) contribute most to alcohol-attributable injuries. METHODS: In all, 8,736 patients, of whom 5,077 were injured, admitted to the surgical ward of the emergency department of Lausanne University Hospital between January 1, 2003, and June 30, 2004, were screened for alcohol use. Eleven groups were constructed on the basis of usual patterns of intake and preattendance drinking. Odds ratios (ORs) comparing injured and noninjured were derived, and alcohol-attributable fractions of injuries were calculated from ORs and prevalence of exposure groups. RESULTS: Risk of injury increased with volume of drinking, HED, and preattendance drinking. For both sexes, the highest risk was associated with low intake, HED, and 4 (women), 5 (men), or more drinks before injury. At the same level of preattendance drinking, high-volume drinkers were at lower risk than low-volume drinkers. In women, the group of low-risk non-HED drinkers taking fewer than 4 drinks suffered 47.5% of the alcohol-attributable injuries in contrast to only 20.4% for men. Low-volume male drinkers with HED had more alcohol-attributable injuries than that of low-volume female drinkers with HED (46.9% vs 23.2%). CONCLUSIONS: Although all groups of drinkers are at increased risk of alcohol-related injury, those who usually drink little but on occasion heavily are at particular risk. The lower risk of chronic heavy drinkers may be due to higher tolerance of alcohol. Prevention should thus target heavy-drinking occasions. Low-volume drinking women without HED and with only little preattendance drinking experienced a high proportion of injuries; such women would be well advised to drink very little or to take other special precautions in risky circumstances.

Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study.

This study presents the results of a multicenter investigation of the efficacy of acamprosate in the treatment of patients with chronic or episodic alcohol dependence. One hundred eighteen patients were randomly assigned to either placebo or acamprosate, and both groups were stratified for concomitant voluntary use of disulfiram. Treatment lasted for 360 days, with an additional 360-day follow-up period. The primary efficacy parameters evaluated were: relapse rate and cumulative abstinence duration (CAD). Results were analyzed according to Intention-To-Treat principles using chi2, t, and multiple regression analyses where appropriate. After 30 days on study medication, 40 of 55 (73%) acamprosate-treated patients were abstinent, compared with 26 of 55 (43%) placebo-treated patients (p = 0.019). The treatment advantage remained throughout the study medication period and was statistically significant until day 270 (p = 0.028). Twenty-seven percent of patients on acamprosate and 53% of patients on placebo had a first drink within the first 30 days of the study. The mean CAD was 137 days (40% abstinent days) for the patients treated with acamprosate and 75 days (21% abstinent days) for the placebo group (p = 0.013). No adverse interaction between acamprosate and disulfiram occurred, and the subgroup who received both medications had a better outcome on CAD than the those on only one or no medication. Acamprosate was well tolerated. Diarrhea was the only significant treatment-induced effect. It was concluded that acamprosate was a useful and safe pharmacotherapy in the long-term treatment of alcoholism. Concomitant administration of disulfiram improved the effectiveness of acamprosate.

Acute alcohol consumption and injury: risk associations and attributable fractions for different injury mechanisms.

OBJECTIVE: Most studies on alcohol as a risk factor for injuries have been mechanism specific, and few have considered several mechanisms simultaneously or reported alcohol-attributable fractions (AAFs)-which was the aim of the current study. METHOD: Data from 3,592 injured and 3,489 noninjured patients collected between January 2003 and June 2004 in the surgical ward of the emergency department of the Lausanne University Hospital (Switzerland) were analyzed. Four injury mechanisms derived from the International Classification of Diseases, 10th Revision, were considered: transportation-related injuries, falls, exposure to forces and other events, and interpersonal violence. Multinomial logistic regression models were calculated to estimate the risk relationships of different levels of alcohol consumption, using noninjured patients as quasi-controls. The AAFs were then calculated. RESULTS: Risk relationships between injury and acute consumption were found across all mechanisms, commonly resulting in dose-response relationships. Marked differences between mechanisms were observed for relative risks and AAFs, which varied between 15.2% and 33.1% and between 10.1% and 35.9%, depending on the time window of consumption (either 6 hours or 24 hours before injury, respectively). Low and medium levels of alcohol consumption generally were associated with the most AAFs. CONCLUSIONS: This study underscores the implications of even low levels of alcohol consumption on the risk of sustaining injuries through any of the mechanisms considered. Substantial AAFs are reported for each mechanism, particularly for injuries resulting from interpersonal violence. Observation of a so-called preventive paradox phenomenon is discussed, and prevention or intervention measures are described.

Functional interaction between the estrogen receptor and CTF1: analysis of the vitellogenin gene B1 promoter in yeast.

Eukaryotic gene expression depends on a complex interplay between the transcriptional apparatus and chromatin structure. We report here a yeast model system for investigating the functional interaction between the human estrogen receptor (hER) and CTF1, a member of the CTF/NFI transcription factor family. We show that a CTF1-fusion protein and the hER transactivate a synthetic promoter in yeast in a synergistic manner. This interaction requires the proline-rich transactivation domain of CTF1. When the natural estrogen-dependent vitellogenin B1 promoter is tested in yeast, CTF1 and CTF1-fusion proteins are unable to activate transcription, and no synergy is observed between hER, which activates the B1 promoter, and these factors. Chromatin structure analysis on this promoter reveals positioned nucleosomes at -430 to -270 (+/-20 bp) and at -270 to - 100 (+/-20 bp) relative to the start site of transcription. The positions of the nucleosomes remain unchanged upon hormone-dependent transcriptional activation of the promoter, and the more proximal nucleosome appears to mask the CTF/NFI site located at - 101 to -114. We conclude that a functional interaction of hER with the estrogen response element located upstream of a basal promoter occurs in yeast despite the nucleosomal organization of this promoter, whereas the interaction of CTF1 with its target site is apparently precluded by a nucleosome.

Drug Use Profile, 2011

Historically, alcohol is the most prevalent substance of use and abuse by adults in Iowa. Research from the Behavioral Risk Factor Surveillance System compiled by the federal Centers for Disease Control and Prevention indicates that almost six of every ten adult Iowans are classified as current drinkers of alcoholic beverages. Further, one in five adult Iowans is classified as a binge drinker of alcoholic beverages, a classification indicative of abuse of, or addiction to, the substance.

A Guide to Workforce Drug Testing in Iowa, October 13, 2010

The purpose of the State of Iowa’s drug testing law—Iowa Code Section 730.5 (& Administrative Code Section 641)—is to enhance worker safety, by creating workplaces that are free of drugs and substance abuse. One tool available to private sector employers is drug testing (inclusive of alcohol testing), that often is coupled with educational efforts as part of a comprehensive drug-free workplace program. Each employer must first decide if drug and/or alcohol testing is appropriate for them. Under Iowa law, workplace drug or alcohol testing is optional for private sector employers. Federal laws or regulations governing drug or alcohol testing supersede state law in Iowa.

A Guide to Workplace Drug Testing in Iowa, October 13, 2010

The purpose of the State of Iowa’s drug testing law—Iowa Code Section 730.5 (& Administrative Code Section 641)—is to enhance worker safety, by creating workplaces that are free of drugs and substance abuse. One tool available to private sector employers is drug testing (inclusive of alcohol testing), that often is coupled with educational efforts as part of a comprehensive drug-free workplace program. Each employer must first decide if drug and/or alcohol testing is appropriate for them. Under Iowa law, workplace drug or alcohol testing is optional for private sector employers. Federal laws or regulations governing drug or alcohol testing supersede state law in Iowa.

Native folding of aggregation-prone recombinant proteins in Escherichia coli by osmolytes, plasmid- or benzyl alcohol-overexpressed molecular chaperones.

When massively expressed in bacteria, recombinant proteins often tend to misfold and accumulate as soluble and insoluble nonfunctional aggregates. A general strategy to improve the native folding of recombinant proteins is to increase the cellular concentration of viscous organic compounds, termed osmolytes, or of molecular chaperones that can prevent aggregation and can actively scavenge and convert aggregates into natively refoldable species. In this study, metal affinity purification (immobilized metal ion affinity chromatography [IMAC]), confirmed by resistance to trypsin digestion, was used to distinguish soluble aggregates from soluble nativelike proteins. Salt-induced accumulation of osmolytes during induced protein synthesis significantly improved IMAC yields of folding-recalcitrant proteins. Yet, the highest yields were obtained with cells coexpressing plasmid-encoded molecular chaperones DnaK-DnaJ-GrpE, ClpB, GroEL-GroES, and IbpA/B. Addition of the membrane fluidizer heat shock-inducer benzyl alcohol (BA) to the bacterial medium resulted in similar high yields as with plasmid-mediated chaperone coexpression. Our results suggest that simple BA-mediated induction of endogenous chaperones can substitute for the more demanding approach of chaperone coexpression. Combined strategies of osmolyte-induced native folding with heat-, BA-, or plasmid-induced chaperone coexpression can be thought to optimize yields of natively folded recombinant proteins in bacteria, for research and biotechnological purposes.

The economic burden of alcohol dependence in europe.

AIMS: To determine the economic burden pertaining to alcohol dependence in Europe. METHODS: Database searching was combined with grey literature searching to identify costs and resource use in Europe relating to alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) or the World Health Organisation's International Classification of Diseases (ICD-10). Searches combined MeSH headings for both economic terms and terms pertaining to alcohol dependence. Relevant outcomes included direct healthcare costs and indirect societal costs. Main resource use outcomes included hospitalization and drug costs. RESULTS: Compared with the number of studies of the burden of alcohol use disorders in general, relatively few focussed specifically on alcohol dependence. Twenty-two studies of variable quality were eligible for inclusion. The direct costs of alcohol dependence in Europe were substantial, the treatment costs for a single alcohol-dependent patient lying within the range euro1591-euro7702 per hospitalization and the annual total direct costs accounting for 0.04-0.31% of an individual country's gross domestic product (GDP). These costs were driven primarily by hospitalization; in contrast, the annual drug costs for alcohol dependence were low. The indirect costs were more substantial than the direct costs, accounting for up to 0.64% of GDP per country annually. Alcohol dependence may be more costly in terms of health costs per patient than alcohol abuse. CONCLUSIONS: This review confirms that alcohol dependence represents a significant burden for European healthcare systems and society. Difficulties in comparing across cost-of-illness studies in this disease area, however, prevent specific estimation of the economic burden.

The influence of drinking pattern, at individual and aggregate levels, on alcohol-related negative consequences.

AIM: To determine the extent drinking patterns (at the individual and country level) are associated with alcohol-related consequences over and above the total alcohol the person consumes. METHODS: Hierarchical linear models were estimated based on general population surveys conducted in 18 countries participating in the GENACIS project. RESULTS: In general, the positive association between drinking pattern scores and alcohol-related consequences was found at both the individual and country levels, independent of volume of drinking. In addition, a significant interaction effect indicated that the more detrimental the country's drinking pattern, the less steep the association between the volume of drinking and its consequences. CONCLUSION: Drinking patterns have an independent impact on consequences over and above the relationship between volume and consequences.

Little evidence that hepatitis C virus leads to a higher risk of mortality in the absence of cirrhosis and excess alcohol intake: the Swiss Hepatitis C Cohort Study.

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (<or=40 g/day) and were not genotype 3, indicated no strong evidence of excess mortality. We found little evidence of excess mortality in hepatitis C infected patients who were not cirrhotic, in the absence of selected risk factors. Our findings emphasize the importance of providing appropriate preventive advice, such as counselling to avoid alcohol intake, in those infected with HCV.

Probing the interaction between feline immunodeficiency virus and CD134 by using the novel monoclonal antibody 7D6 and the CD134 (Ox40) ligand.

The feline immunodeficiency virus (FIV) targets activated CD4-positive helper T cells preferentially, inducing an AIDS-like immunodeficiency in its natural host species, the domestic cat. The primary receptor for FIV is CD134, a member of the tumor necrosis factor receptor superfamily, and all primary viral strains tested to date use CD134 for infection. We examined the expression of CD134 in the cat using a novel anti-feline CD134 monoclonal antibody (MAb), 7D6, and showed that as in rats and humans, CD134 expression is restricted tightly to CD4+, and not CD8+, T cells, consistent with the selective targeting of these cells by FIV. However, FIV is also macrophage tropic, and in chronic infection the viral tropism broadens to include B cells and CD8+ T cells. Using 7D6, we revealed CD134 expression on a B220-positive (B-cell) population and on cultured macrophages but not peripheral blood monocytes. Moreover, macrophage CD134 expression and FIV infection were enhanced by activation in response to bacterial lipopolysaccharide. Consistent with CD134 expression on human and murine T cells, feline CD134 was abundant on mitogen-stimulated CD4+ T cells, with weaker expression on CD8+ T cells, concordant with the expansion of FIV into CD8+ T cells with progression of the infection. The interaction between FIV and CD134 was probed using MAb 7D6 and soluble CD134 ligand (CD134L), revealing strain-specific differences in sensitivity to both 7D6 and CD134L. Infection with isolates such as PPR and B2542 was inhibited well by both 7D6 and CD134L, suggesting a lower affinity of interaction. In contrast, GL8, CPG, and NCSU were relatively refractory to inhibition by both 7D6 and CD134L and, accordingly, may have a higher-affinity interaction with CD134, permitting infection of cells where CD134 levels are limiting.

The effect of exercise, alcohol or both combined on health and physical performance.

Alcohol (ethanol) is consumed on a daily basis by a large fraction of the population, and in many countries, light-to-moderate alcohol consumption is considered as an integral part of the diet. Although the relationship between alcohol intake and obesity is controversial, regular consumption of alcohol, through its effects in suppressing fat oxidation, is regarded as a risk factor for weight gain, increased abdominal obesity and hypertriglyceridemia. Indeed, alcohol taken with a meal leads to an increase in postprandial lipemia-an effect on postprandial metabolism that is opposite to that observed with exercise. Furthermore, although regular exercise training and/or a preprandial exercise session reduce postprandial lipemia independently of alcohol ingestion, the exercise-induced reduction in postprandial lipemia is nonetheless less pronounced when alcohol is also consumed with the meal. Whether or not alcohol influences exercise and sport performance remains contradictory. It is believed that alcohol has deleterious effects on the performance, although it may contribute to reduce pain and anxiety. The alcohol effects on sports performance depend on the type and dosage of alcohol, acute vs chronic administration, the alcohol elimination rate as well as the type of exercise.

Effect of a small dose of alcohol on the endurance performance of trained cyclists.

AIM: The aim of this study was to investigate the effect of an acute small ethanol (EtOH) dose (0.5 ml EtOH/kg fat-free mass, combined with carbohydrate) in a drink on endurance performance of trained cyclists. METHODS: Thirteen well-trained male cyclists took part in this study. A 60-min cycling endurance performance test (time trial) was performed in a calorimetric chamber after drinking an EtOH (30 +/- 1.8 ml) or a non-EtOH control (C) drink. RESULTS: Overall, EtOH induced a significant decrease in the average cycling power output (PO) (EtOH: 233 +/- 23 W versus C: 243 +/- 24 W, P < 0.01). The time course of mechanical PO showed an early decrease during the EtOH trial as compared to C (P < 0.01). Due to the lower PO, oxygen consumption, carbon dioxide production and glucose oxidation were significantly lower (P < 0.05) as compared to C. Relative to PO, heart rate response and ratings of perceived exertion (RPE) were increased by EtOH as compared to C (P < 0.05). In contrast, EtOH did not influence gross work efficiency, glycaemia and blood lactate concentration. CONCLUSIONS: These results show that the acute low dose of EtOH decreased endurance performance. An increase of cardio-vascular strain and psychobiological mechanisms may explain this decrease of endurance performance.

Therapeutic drug monitoring and pharmacogenetic tests as tools in pharmacovigilance.

Therapeutic drug monitoring (TDM) and pharmacogenetic tests play a major role in minimising adverse drug reactions and enhancing optimal therapeutic response. The response to medication varies greatly between individuals, according to genetic constitution, age, sex, co-morbidities, environmental factors including diet and lifestyle (e.g. smoking and alcohol intake), and drug-related factors such as pharmacokinetic or pharmacodynamic drug-drug interactions. Most adverse drug reactions are type A reactions, i.e. plasma-level dependent, and represent one of the major causes of hospitalisation, in some cases leading to death. However, they may be avoidable to some extent if pharmacokinetic and pharmacogenetic factors are taken into consideration. This article provides a review of the literature and describes how to apply and interpret TDM and certain pharmacogenetic tests and is illustrated by case reports. An algorithm on the use of TDM and pharmacogenetic tests to help characterise adverse drug reactions is also presented. Although, in the scientific community, differences in drug response are increasingly recognised, there is an urgent need to translate this knowledge into clinical recommendations. Databases on drug-drug interactions and the impact of pharmacogenetic polymorphisms and adverse drug reaction information systems will be helpful to guide clinicians in individualised treatment choices.