Nature and Treatment of Comorbid Alcohol Problems and Post Traumatic Stress Disorder Among American Military Personnel and Veterans.

Many service members and veterans seeking treatment for alcohol problems also have post-traumatic stress disorder (PTSD). This article considers the effectiveness of treating alcohol problems and PTSD simultaneously. The authors begin by summarizing the extent of excessive alcohol use among military service members and veterans. They then explore the relationship between combat exposure and subsequent alcohol use; identify and briefly describe evidence-based treatments for alcohol problems and PTSD, separately; and review research on the effects of single treatments for both PTSD symptoms and alcohol use.

Group dynamics challenges: Insights from Biosphere 2 experiments.

Successfully managing group dynamics of small, physically isolated groups is vital for long duration space exploration/habitation and for terrestrial CELSS (Controlled Environmental Life Support System) facilities with human participants. Biosphere 2 had important differences and shares some key commonalities with both Antarctic and space environments. There were a multitude of stress factors during the first two year closure experiment as well as mitigating factors. A helpful tool used at Biosphere 2 was the work of W.R. Bion who identified two competing modalities of behavior in small groups. Task-oriented groups are governed by conscious acceptance of goals, reality-thinking in relation to time and resources, and intelligent management of challenges. The opposing unconscious mode, the "basic-assumption" ("group animal") group, manifests through Dependency/Kill the Leader, Fight/Flight and Pairing. These unconscious dynamics undermine and can defeat the task group's goal. The biospherians experienced some dynamics seen in other isolated teams: factions developing reflecting personal chemistry and disagreements on overall mission procedures. These conflicts were exacerbated by external power struggles which enlisted support of those inside. Nevertheless, the crew evolved a coherent, creative life style to deal with some of the deprivations of isolation. The experience of the first two year closure of Biosphere 2 vividly illustrates both vicissitudes and management of group dynamics. The crew overrode inevitable frictions to creatively manage both operational and research demands and opportunities of the facility, thus staying 'on task' in Bion's group dynamics terminology. The understanding that Biosphere 2 was their life support system may also have helped the mission to succeed. Insights from the Biosphere 2 experience can help space and remote missions cope successfully with the inherent challenges of small, isolated crews.

Estimating the prevalence of drinking problems among physicians.

OBJECTIVE: Surveys assessing alcohol use among physicians have most commonly employed the Alcohol Use Disorders Identification Test (AUDIT) or the AUDIT-C, the most common short version of the AUDIT. As with other screeners, prevalence estimation is dependent on the accuracy of the test as well as choice of the cutoff value. The aim of the current study is to derive more precise prevalence estimates of alcohol problems in physicians by correcting for false-positive and false-negative results. METHOD: In the context of a survey, the AUDIT was sent out via email or standard postal service to all 2484 physicians in Salzburg, Austria. A total of 456 physicians participated. A published correction formula was used to estimate the real prevalence of alcohol use problems. RESULTS: Applying a cutoff of 5 points for the AUDIT-C, 15.7% of female and 37.7% of male physicians screened positive. Use of a correction based on general population data and the sensitivity and specificity of the AUDIT-C resulted in much lower prevalence rates: 4.0% for female and 9.5% for male physicians. Using the full AUDIT, 19.6% of the female physicians and 48% of the male physicians were screened positive. Using the correction, the estimated prevalence rates for females and males were 6.3% and 15.5%, respectively. CONCLUSIONS: Our findings demonstrate that uncorrected screening results may markedly overestimate the prevalence of physicians drinking problems.

Assessing the drinking status of liver transplant patients with alcoholic liver disease.

The accurate assessment of drinking by patients with alcoholic liver disease is important both before and after liver transplantation. Unfortunately, self-reports by these individuals often underestimate their actual alcohol consumption. Several recently developed biochemical measures can provide additional information on a patient's use of alcohol. This article describes ethyl glucuronide, ethyl sulfate, phosphatidyl ethanol, and carbohydrate-deficient transferrin as biomarkers of drinking and summarizes research dealing with their application in patients with alcohol use disorders who are candidates for or recipients of liver transplantation. The article also offers suggestions for enhancing the reliability of self-report measures of drinking status.

The alcohol use disorders identification test: an update of research findings.

BACKGROUND: The Alcohol Use Disorders Identification Test (AUDIT) has been extensively researched to determine its capability to accurately and practically screen for alcohol problems. METHODS: During the 5 years since our previous review of the literature, a large number of additional studies have been published on the AUDIT, abbreviated versions of it, its psychometric properties, and the applicability of the AUDIT for a diverse array of populations. The current article summarizes new findings and integrates them with results of previous research. It also suggests some issues that we believe are particularly in need of further study. RESULTS: A growing body of research evidence supports the criterion validity of English version of the AUDIT as a screen for alcohol dependence as well as for less severe alcohol problems. Nevertheless, the cut-points for effective detection of hazardous drinking as well as identification of alcohol dependence or harmful use in women need to be lowered from the originally recommended value of 8 points. The AUDIT-C, the most popular short version of the AUDIT consisting solely of its 3 consumption items, is approximately equal in accuracy to the full AUDIT. Psychometric properties of the AUDIT, such as test-retest reliability and internal consistency, are quite favorable. Continued research is urged to establish the psychometric properties of non-English versions of the AUDIT, use of the AUDIT with adolescents and with older adults, and selective inclusion of alcohol biomarkers with the AUDIT in some instances. CONCLUSIONS: Research continues to support use of the AUDIT as a means of screening for the spectrum of alcohol use disorders in various settings and with diverse populations.

Ethyl sulphate: a direct ethanol metabolite reflecting recent alcohol consumption.

BACKGROUND: Ethyl sulphate (EtS), a direct ethanol metabolite, appears to offer potential as a biomarker for recent alcohol consumption. Although its window of assessment is similar to that of ethyl glucuronide (EtG), there are differences between the two markers in their pathways for formation and degradation. AIMS: (a) To assess the excretion of EtS compared to EtG and ethanol in drinking experiments with healthy volunteers, and (b) to elucidate the possibility of using the two metabolites for monitoring abstinence in substance use disorder patients during rehabilitation treatment. DESIGN, SETTING, PARTICIPANTS: (a) Nine drinking experiments were performed by six healthy volunteers (two females, four males), with a mean age of 34.1 years (20-62), average oral intake of 0.2 g/kg ethanol (0.1-0.61), and having 74 spot urine samples. (b) Thirty-six substance abuse patients (mean age 41.9 years, 20-59; 22 males, 14 females) in a rehabilitation programme after withdrawal, producing 98 urine samples. Ethyl glucuronide and ethyl sulphate were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) using d5-EtG and d5-EtS, respectively, as an internal standard. FINDINGS: (a) VOLUNTEERS: EtG and EtS were detectable for up to 36 hours and reached the limits of determination in urine at 20.6 hours and 21.2 hours (median), respectively, after ethanol intake. EtG-100 (standardized to a creatinine of 100 mg/dl) reached its maximum level at 2.8 hours and EtS-100 at 2.1 hours (median) after the beginning of the experiment. Of the ethanol ingested, 0.022% was excreted as EtS in one volunteer. Eight samples were positive for EtS only and six for EtG only. Spearman's rank correlation coefficients of 0.84 (P < 0.0001) between EtG and EtS and 0.87 (P < 0.0001) between EtG-100 and EtS-100 were found. (b) PATIENTS: of the 98 urine samples evaluated, 27 were positive for EtS and of these only 20 were also positive for EtG. Spearman's rank correlation coefficients of 0.84 (P < 0.0001) between EtG and EtS and 0.82 (P < 0.0001) between EtG-100 and EtS-100 were found. CONCLUSIONS: The data from patients and volunteers suggest that the direct ethanol metabolite ethyl sulphate has the potential to serve as a biomarker of recent ethanol intake. Because EtG and EtS are formed via different pathways they might be used conjointly, thereby increasing sensitivity.

No significant effect of acute moderate alcohol intake on leptin levels in healthy male volunteers.

As, for ethical reasons, it is difficult to investigate by an experiment the effect of acute intoxication on leptin levels in alcoholics, we tested the hypothesis of lowered levels as an effect of acute ethanol intake in healthy volunteers. The subjects comprised (1) 17 healthy male participants, recruited via newspaper advertisements [age 29+/-3.75 years, body mass index (BMI) 24.3+/-3.5, leptin at baseline 3.3+/-3.1 ng/ml]; (2) for comparison, leptin levels of 16 male alcoholic patients at day 1 of withdrawal were used. They were characterized as follows: (mean, median, standard deviation and range) age in years (41.1, 40.5, 10.2, 24, 57), BMI (23.3, 21.7, 5.4, 16.6, 37.5), 1,032 g of ethanol (median) consumed within the last 7 days, leptin levels 2.3 mg/ml. A placebo-controlled double-blind trial was performed. Leptin levels of blood samples were taken at baseline (t(1)), before ethanol intake (t(2)), when blood alcohol had reached its maximum (t(3)) and the morning after (t(4)). The oral dose of ethanol administered was 0.6 g/kg ethanol. (1) VOLUNTEERS: (a) the ethanol and placebo group exhibited leptin levels corresponding closely with levels measured at baseline (t(1)) (rs=0.85, p<0.0001) and follow-up (t(4)) (rs=0.768, p<0.0001). (b) Leptin levels for the placebo and the alcohol-consuming (verum) group did not differ significantly at baseline, after ethanol intake or on the morning after [Mann-Whitney U-test (p=0.669, p=1.0 and p=0.887, respectively)]. (2) Leptin levels in relation to BMI did not significantly differ at any measurement time in either group. (3) Leptin levels/BMI of the healthy volunteers at t(1) and t(4) were not significantly different from those of 16 alcoholics. The data do not support the hypothesis of a significant effect of acute moderate alcohol intake on leptin levels in healthy volunteers.

Suicide in the Army: a review of current information.

This article summarizes findings on demographic factors, distal risk factors, and proximal risk factors for suicide and reports recent data on suicide by Army personnel. In addition, the article offers recommendations to reduce the risk of suicide and suicide attempt in the Armed Services and suggests possible directions for future research on suicide in the military.

Emerging biomarkers: new directions and clinical applications.

This article summarizes content proceedings of a symposium held at the 2004 Research Society on Alcoholism Scientific Annual Meeting in Vancouver, Canada. The chairs were Friedrich M. Wurst and Raye Litten. The presentations were (1) Introduction, by Raye Litten; (2) Direct Ethanol Metabolites--On the Threshold From Science to Routine Use, by Friedrich M. Wurst; (3) Sialic Acid Index of Plasma Apolipoprotein J (SIJ) as a Viable Marker for Chronic Alcohol Consumption, by Philippe Marmillot; (4) The Emergence of Ethyl Glucuronide (EtG) Testing as a Tool in Monitoring Healthcare Professionals, by Gregory E. Skipper; (5) Application of Biomarkers for Alcohol Use Disorders in Clinical Practice, by Tim Neumann; (6) Utility of Biomarkers in Assessing the Efficacy of Medications for Treating Alcoholism, by Marty Javors; and (7) Discussion, by Raye Litten.

Ethyl glucuronide: a biomarker to identify alcohol use by health professionals recovering from substance use disorders.

AIMS: Physicians recovering from substance-related disorders are usually allowed to return to practice if they agree to remain abstinent from drugs, including alcohol, and to undergo random urine testing. Over 9000 physicians are currently involved in such monitoring programs in the US. To date, it has been difficult to adequately monitor abstinence from alcohol due to the short half-life of alcohol and no other highly specific marker. Ethyl glucuronide (EtG), a direct metabolite of alcohol, offers an extended window for assessment of drinking status (up to 5 days). Our aim was to assess the potential value of EtG testing in abstinence-based monitoring programs. PATIENTS AND METHODS: Urine samples were obtained from 100 participants in a physician monitoring program and additional samples were subsequently obtained 'for cause', 'to verify positive urine alcohol, when drinking was denied' and 'in high risk individuals'. All participants had signed contracts agreeing to remain abstinent from mood-altering drugs, including alcohol, and had agreed to random urine testing. EtG was determined using LC/MS-MS in addition to standard testing. The main outcome measure were urine specimens positive for EtG versus those positive based on standard testing for alcohol and other drugs. RESULTS: Among the initial 100 random samples collected, no sample was positive for alcohol using standard testing; however, seven were positive for EtG (0.5-196 mg/l), suggesting recent alcohol use. Subsequent EtG testing was performed clinically during the course of monitoring. Of the 18 tests performed to date, eight of eight tests performed 'for cause' were positive for EtG but negative for all other drugs including urine alcohol. All eight were confirmed positive by self reported drinking by the patient when confronted regarding the positive test result. Of six tests performed to 'confirm a positive urine alcohol' two were positive for EtG and confirmed positive by self reported drinking. For the other four samples, especially as two are from a diabetic, in vitro fermentation of ethanol is discussed. CONCLUSIONS: These data suggest that physicians in monitoring programs have a higher rate of unrecognized alcohol use than previously reported. Incorporation of EtG testing into alcohol abstinence monitoring can strengthen these programs.

Concentration of fatty acid ethyl esters in hair of alcoholics: comparison to other biological state markers and self reported-ethanol intake.

AIMS: In a variety of clinical and forensic situations long term use of alcohol must be monitored. In this project we explore the utility of fatty acid ethyl esters (FAEE) in this regard. Additionally, we propose a cut-off value of FAEE to distinguish teetotallers/moderate/social drinkers from alcoholics or individuals drinking at harmful levels. PATIENTS AND METHODS: FAEE levels from 18 alcohol-dependent patients in detoxification were contrasted with those of 10 social drinkers and 10 teetotallers. FAEE in hair were determined, using headspace solid phase microextraction and gas chromatography mass spectrometry. C(FAEE), as sum of the concentrations of four esters, was compared to a major FAEE, ethyl palmitate. PEth was measured in heparinized whole blood with a high pressure liquid chromatography (HPLC) method. Drinking validation criteria include self reports, phosphatidyl ethanol (PEth) in whole blood as well as the traditional markers of heavy drinking, gamma glutamyl transpeptidase (GGT), mean corpuscular volume (MCV) and carbohydrate deficient transferrin (CDT). RESULTS: Receiver-operating characteristic (ROC) curve analysis for C(FAEE), indicated a sensitivity of 100% and a specificity of 90% for a cut-off of 0.29 ng/mg. By using a cut-off of 0.4 ng/mg, C(FAEE) identified 94.4% correctly. C(FAEE) and ethyl palmitate were significantly associated (r = 0.945; P < 0.001) as were C(FAEE) and PEth (r = 0.527; P = 0.025). No significant correlation was found between C(FAEE) and total grams of ethanol consumed last month, blood-alcohol concentration at admission to the hospital, CDT, MCV, or GGT. Among the serum and blood markers, %CDT identified 47.1%, MCV 38.8% and GGT 72.2% of patients with chronic intake of higher amounts of ethanol correctly, whereas PEth achieved 100% accuracy. CONCLUSIONS: The data suggest that C(FAEE) is a potentially valuable marker of chronic intake of high quantities of ethanol. Furthermore, the results indicate that a reasonable and provisional FAEE cut-off to distinguish between social/moderate and heavy drinking/alcoholism in hair is 0.4 ng/mg.

Recommendations on use of biomarkers in alcoholism treatment trials.

BACKGROUND: Biochemical markers of heavy drinking are playing increasingly prominent roles in alcohol treatment efficacy studies, especially in those designed to evaluate medications. Among these roles are serving as inclusion or exclusion criteria for research participants, corroboration of self-report of drinking status, assessment of the safety of the agent being evaluated, and determination of treatment outcome. METHODS: Recent alcohol medication development trials that included biomarker information were reviewed and critiqued from the perspectives of how biomarker measures were used and how findings on them were reported. RESULTS: Although generally the application of biomarkers as inclusion criteria is not recommended, they may aid in exclusion of potential subjects (e.g., elevated liver function measures in trials of agents that could result in liver damage). Biomarkers are most commonly used as indicators of outcome, usually serving as secondary outcome variables. The relationship of outcome findings on biomarker and self-report measures is positive, but only moderate. As used to date, biomarkers of drinking tend to be less sensitive than well-standardized and properly administered self-report measures. Nevertheless, they do provide a useful, unique source of information on drinking status. CONCLUSIONS: The contribution of biomarkers to alcoholism clinical research would be enhanced if certain design strategies were incorporated into their application and if critical information were included in the research publication. This article offers a series of recommendations to improve on their use in a research context.

Use of biomarkers of heavy drinking in health care practice.

Several biochemical tests are available to screen for heavy drinking in patients. Most of these (e.g., liver function tests and macrocytic volume) rise due to adverse effects of alcohol on organs or the organ's functions. Carbohydrate-deficient transferrin, however, seems to elevate because of the direct action of alcohol or one of its metabolites. A second valuable contribution of biomarkers is identification of relapse events in recovering alcoholics that either would not be voluntarily reported or reported only much later. Finally, providing feedback to patients in treatment based on their biomarker values and changes in them during the course of treatment can enhance motivation, a key component in recovery from alcohol problems. The current article offers a clinical rationale for routine use of biomarkers of heavy drinking in health care practice and proposes recommendations on how they might be best used.

Assessment of alcoholic patients: advances and future challenges.

Noteworthy advances have been made in methods of assessing patients suffering alcohol problems. More than one hundred measures are now available to assist clinicians and researchers in screening for such problems, diagnosing them, and developing treatment plans individualized according to relevant patient characteristics. This chapter reviews progress in assessment supporting each of these activities and suggests directions for future research. It concludes by identifying a series of research issues that cut across multiple domains of alcohol assessment.

Biomarkers as aids to identification of relapse in alcoholic patients.

Since return to drinking is common in patients recovering from alcoholism, recognition of relapse should be an important component of treatment. Recurrent assessment with biochemical measures can provide clinicians with useful information on the drinking status of their patients. This chapter addresses issues surrounding the importance of early detection of relapse, describes biochemical markers that may assist in this, reviews relevant scientific investigations, and offers recommendations to researchers and clinicians.

The Alcohol Use Disorders Identification Test (AUDIT): a review of recent research.

BACKGROUND: Efficient, inexpensive screening for early stage alcohol problems is important in health care settings. The Alcohol Use Disorders Identification Test (AUDIT) has been studied extensively to establish its value in this regard. METHODS: A literature search that used EtOH as a database was conducted to identify studies published on the AUDIT through September 2001. Keywords used for the search were "Alcohol Use Disorders Identification Test" and "AUDIT." All studies reporting psychometric properties of the measure were reviewed with particular attention being given to the period 1996 and later. A small number of additional references were located by noting their citation in other studies reviewed. RESULTS: Although more research is needed on non-English versions to establish their psychometric properties, at least in its English edition, the AUDIT demonstrates sensitivities and specificities comparable, and typically superior, to those of other self-report screening measures. Test-retest reliability and internal consistency are also quite favorable. For males, the AUDIT-C, a shortened version of the AUDIT, appears approximately equal in validity to the full scale. CONCLUSIONS: Recent research continues to support use of the AUDIT as a means of screening for alcohol use disorders in health care settings in the United States.