Search

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.

Chaplains can play a unique and valuable role in the treatment of alcohol dependence, a condition that has physical, psychological, and spiritual dimensions. To best fulfill this role, chaplains need to have a broad understanding of the nature of alcohol problems and current strategies for effectively interacting with individuals who have these problems, especially those with severe problems, and with their families. This article is designed to expand the chaplain’s knowledge about alcohol use disorders as well as evidence-based treatments and to offer recommendations on how chaplains can promote recovery of individuals with alcohol-related problems.

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.

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

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 inhealthy 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 I 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), 1032g of ethanol (median) consumed within the last 7 days, leptin levels 2.3mglml. A placebo-controlled double-blind trial teas 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 ) (r s = 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.

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.

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.

This article represents the proceedings of a symposium held at the 2001 RSA meeting in Montreal, Canada. The organizer and chair was Barbara A. Flannery and the discussant was Raye Z. Litten. The presentations were (1) The use of biomarkers in alcohol-dependence treatment trials, by John P. Allen; (2) Strategies for enhancing patient compliance in clinical treatment trials, by Helen M. Pettinati; (3) The predictive utility of an alcohol-craving measure, by Barbara A. Flannery; (4) What should be the primary outcome measures in a clinical trial, by Damaris J. Rohsenow; (5) Innovative strategies for assessing functional outcomes in alcoholism treatment clinical trials, by Ron A. Cisler.

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.

Background: Increasingly, biomarkers are being incorporated into the research design of clinical trials on medications to reduce drinking in alcoholics. To date, however, there has been little analysis of the unique roles that biomarkers can play in such investigations or of the practical and conceptual considerations that surround their best use in this context. Methods: Clinical trials of alcoholism medications published between 1985 and the present were abstracted to determine how biomarkers were used and how changes in them related to self-report measures of drinking. Results: Six uses of biomarkers were identified: determination of subjects to be included or excluded in the trial; description of baseline sample characteristics; primary and secondary outcome assessment; corroboration of self-reports of drinking status; specification of patients likely to respond to the medication; and evaluation of drug safety. Conclusion: Use of biomarkers in such studies appears warranted, particularly as an objective source of information on treatment efficacy that can be considered with patient self-report measures of drinking status. Biomarkers related to liver functioning also can assist in determination of drug safety for medications metabolized by the liver.

Naltrexone has been demonstrated in western studies to be a useful pharmacological adjunct within treatment programmes for alcoholic patients. We report the first study of its efficacy and usefulness in an Asian region. This project was designed to allow naltrexone's performance to be assessed under routine clinical conditions but with patients selected on the basis of their being likely to comply. Following in-patient detoxification, 53 male alcohol-dependent patients admitted to the Alcohol Treatment Centre at Woodbridge Hospital, Singapore, were enrolled in a 12-week, placebo-controlled trial of naltrexone hydrochloride (50 mg/day). Subjects were randomized on a 2:1 basis, with 35 receiving naltrexone and 18 receiving placebo. Analyses identified that a higher percentage of naltrexone patients completed the study (40% vs. 22%). In the study non-completers, the dropout rate due to drinking relapse was also lower in the naltrexone group (9% vs. 43%). Of the 39 patients for whom drinking status over the trial could be ascertained, fewer naltrexone-treated patients drank (33% vs. 53%). Alcohol craving scores also showed a selective and distinct reduction in the naltrexone-treated group. Results suggest that naltrexone may be an effective and safe aid to treatment of alcohol dependent patients in Asian patients, for whom the aims are to reduce alcohol craving and drinking reinstatement, but where compliance is likely to be low.

Background: Transferrin is a globular protein synthesized in the liver that is responsible for iron transport in plasma. The structure of the molecule consists of two carbohydrate residues to which six sialic acid moieties can be attached. After periods of chronic, heavy alcohol consumption, carbohydrate-deficient transferrin (CDT) isoforms often increase, which makes CDT a useful marker in screening for alcohol abuse and monitoring progress of alcoholics in treatment. However, the precise mechanism behind CDT increase remains unknown. Methods: A review of the most relevant literature on CDT was conducted with a computer-assisted literature search. Results: During the past several years, a number of studies have explored possible mechanisms that may account for the alcohol-induced increase of CDT. An inhibition of protein synthesis and a general effect of alcohol on protein glycosylation have been reported. Although the exact mechanisms that underlie production of CDT are not yet fully understood, possible bases for the phenomenon are presented in this article. Conclusions: Experimental findings indicate that the ethanol-induced effect on glycoprotein metabolism is a multistep process in which protein transport and changes of enzyme activity may play an important role.

Although the primary use of biochemical markers of heavy drinking is to assist in screening for alcohol problems, laboratory tests may also aid in early identification of relapse. This report reviews research findings on a new marker, carbohydrate deficient transferrin (CDT), in alcoholics receiving treatment or in follow-up. It also offers recommendations on how CDT may be employed by clinicians monitoring drinking status.

Physiologic, behavioral, and social factors contribute to dependence on alcohol, nicotine, and other drugs. During the past decade substantial research has focused on identification/development of medications to assist in reducing urge to use these substances. This article describes these agents and reviews recent research findings on them.

Eight previous investigations have suggested that conjoint consideration of findings on tests for gamma glutamyl transpeptidase (GGT) and carbohydrate deficient transferrin (CDT) substantially enhances sensitivity of screening for alcohol problems while minimally diminishing specificity. Using results from a large clinical trial, the current study evaluated the two tests singly and in combination as measures of three clinically important treatment outcome criteria: any drinking, at least one day of heavy drinking, and at least three consecutive days of heavy drinking during the past month. When scored by quartile, CDT is slightly better at screening for alcohol problems in males than GGT. However, CDT seems less accurate in females than GGT. Use of the two tests in consort moderately improves the individual test accuracy in predicting drinking status for both genders.

Approximately 14 million Americans suffer from alcohol abuse and dependen~e,’~ and drinking remains the most common cause of liver-related mortality in the United States. Forty-four percent of the 26,000 annual deaths from liver cirrhosis are attributed to alcohol use. Even this is likely to be an underestimate because certifying physicians may not be familiar with the decedent’s drinking history or may desire to protect the family from the stigma of a family member being an alcoholic.10 Alcoholic liver disease is also an important cause of morbidity. It has been estimated that between 15% and 30% of heavy drinkers develop advanced liver disease.I9 In 1990, cirrhosis was listed as a diagnosis on approximately 1% of discharges from nonfederal short-stay hospitals for those 15 years and older and was the principal diagnosis for 0.2% of the discharges. Underestimation of alcoholic liver disease on hospital discharge records may exceed that for death certificate^.^^ Because of the adverse effects of alcohol on the liver, alcoholdependent and alcohol-abusing patients commonly are seen in many hepatologists’ practices. Although findings on the physical examination and laboratory tests may provide clues, the diagnosis of alcoholism depends on the history provided by patients and their relatives. The two most commonly employed sets of criteria are the American Psychiatric Association‘s Diagnostic and Statistical Manual of Mental Disorders, ed 4 (DSM-IV)’ and in the World Health Organization’s International Classification of Diseases, 10th rev (ICD-10).36 Both are based on symptoms of alcohol dependence and abuse rather than specific thresholds of drinking frequency, quantity, or patterns. The term alcoholism has been dropped in favor of two distinct categoriesalcokol abuse and alcohol dependence. Alcoholic liver

Research on the core version of the Alcohol Use Disorders Identification Test (AUDIT) is reviewed. Sensitivities and specificities of the AUDIT or criteria of current hazardous use and, to a slightly lesser extent, lifetime alcohol dependence are high. In general, AUDIT scores are at least moderately related to other self-report alcohol screening tests. Several studies also show them as correlated with biochemical measures of drinking. Results of the AUDIT have also been associated with more distal indicators of problematic drinking. Indices of internal consistency, including Cronbach's alpha and item-total correlations, are generally in the 0.80's. Future directions for research on the AUDIT are suggested.

Biochemical markers can serve as valuable tools in screening for problematic drinking, determining whether a health problem is likely alcohol related, and monitoring alcoholics for relapse during and after treatment. Furthermore, biochemical markers can assist in forensic investigations; in identification of public health, safety, and transportation workers who may drink excessively and who, as a result, may put others at risk; in evaluation of efficacy of treatments for alcohol abuse; and in recognition of early phase alcohol-related tissue damage. Within all of these contexts, a biochemical marker or set of markers may corroborate verbal reports or may provide valuable independent information on alcohol use when an individual is unable or unwilling to offer valid data about alcohol consumption.

The current investigation determined that military personnel who drink heavily differ from those who drink moderately in the practice of nine behaviors often associated with unhealthy lifestyle. In particular, excessive drinkers were found to smoke more, drive dangerously more frequently, and consume saturated fats more often. The project further found that the relationship of excessive drinking to these activities is mediated by age, marital status, and race, although not by gender or rank. Implications of the findings for prevention and treatment are suggested.

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.

Current trends in conceptions of alcohol problems and provision of health care put increased emphasis on identifying individuals whose alcohol use and problems cover a range of severity. The purpose of this study is to begin to provide information on the relative utility of self-report measures designed to identify (screen for) individuals with alcohol problems. To achieve this goal, the empirical literature on contrasts of self-report screening measures was reviewed, and 13 relevant studies across diverse settings and subject populations were identified. The review showed that the CAGE, the Michigan Alcoholism Screening Test (MAST), and the short MAST (sMAST) have been the most widely studied self-report instruments to screen for alcohol problems. Direct comparisons show the MAST to be more sensitive than the CAGE, but with elderly patients the CAGE may perform better than the MAST. Furthermore, available data suggest that the CAGE and the sMAST perform comparably. Finally, the CAGE, MAST, and sMAST all perform best when predicting criteria most similar to those the instruments were designed to reflect. The study concludes with a discussion of priorities for research on screening instruments.

The clinical practice of alcoholism treatment can be enhanced by the judicious use of standardized psychometric instruments to characterize clients during the course of treatment. Knowledge of key behavioral, personality, and alcohol-specific factors will increase the clinician's ability to select the most appropriate treatment option, or, even if treatment options are limited, at least to develop a treatment plant with the patient's unique needs in mind. Monitoring of progress towards treatment goals can also be facilitated by the use of selected assessment tools. Seven examples of well-validated instruments are discussed, with suggestions on how data derived from them may be applied in the treatment planning process.

A broad range of psychological and laboratory tests have been developed to assist in identification and treatment of alcoholism. The following measures are reviewed: Self-Administered Alcoholism Screening Test, Clinical Institute Withdrawal Assessment, Alcohol Dependence Scale, Inventory of Drinking Situations, Situational Confidence Questionnaire, Alcohol Expectancy Questionnaire, and Addiction Severity Index. Currently available and promising laboratory tests for alcoholism screening are also briefly described. Finally, comments are offered on the role of assessment in treatment planning and needs for additional psychometric research.

Several earlier studies have reported clinically relevant personality correlates of high vs low scores on the MacAndrew Scale ( Mac) of the MMPI. Unfortunately, these projects have not adjusted for age or nature of abuse. Also, most have assumed that the personality correlates are the same for female patients as for male patients. This study attempts to address these deficiencies. Even after correcting for age and diagnosis, high Mac patients differ from low Mac patients on major scales of the MMPI. The pattern of such differences varies considerably between men and women. Substance abuse treatment implications of these differences are discussed.

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.

Individuals with alcohol problems are disproportionately represented in the primary care population. In that setting, 11% to 20% of patients meet diagnostic criteria for alcohol dependence or abuse.1 The family physician’s role in the care of patients with alcohol problems may include screening, brief intervention, identification of affected family members, pharmacotherapy for craving, detoxification, treatment of associated medical problems, and referral for consultation and rehabilitation.2,3

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.

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.

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.

Background. Misuse of alcohol is associated with a range of medical problems. Fortunately, a simple pencil-and-paper measure, the Alcohol Use Disorders Identification Test, can effectively and efficiently screen for early-stage alcohol abuse as well as provide the physician information that can assist in brief intervention. Objective. The objective of this article is to briefly summarize research published on the Alcohol Use Disorders Identification Test and suggest its potential role in brief intervention in primary care settings. Methods. Scientific literature on the Alcohol Use Disorders Identification Test though 2000 was reviewed and synthesized to address issues relevant to use of the test in primary health care settings. Results. The Alcohol Use Disorders Identification Test is quite sensitive and specific and compares favorably with alternative self-report screens for alcohol problems.

The relationships of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT) and their mathematical combination (gamma-CDT) with self-reported diseases were evaluated in a large cross-sectional risk factor survey. Significant gender effects were observed in associations of the markers with several medical conditions as well as with general health care utilization. In men, CDT was associated with rheumatoid arthritis. In both genders, GGT was positively associated with hypertension and diabetes. gamma-CDT was positively associated with hypertension in males and with asthma in females. This general population study demonstrates that these markers, although most commonly used to assess alcohol misuse, might also serve as health risk indicators.

Although assessment in the field of alcoholism treatment is generally verbal in nature, biological tests can also provide counselors and program evaluators useful and unique information. Five such laboratory measures are briefly described, with particular emphasis on carbohydrate deficient transferrin, a biomarker recently approved by the FDA. Applications for laboratory tests in alcohol screening, motivating patients, and monitoring treatment progress are also proposed.

The dose response to alcohol use of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and their combination (gamma-CDT) was studied in an age- and gender-stratified, random sample from Finland in 1997. A linear association with a threshold between alcohol consumption and the three markers was observed. Body mass index was negatively associated with CDT and positively with GGT Age was positively associated with GGT and gamma-CDT In conclusion, CDT appears to be an early phase marker of alcohol consumption. The combined marker, gamma-CDT, was less associated with factors such as body mass index but more strongly correlated with alcohol consumption than were the two markers separately.

Over the past decade, research on medications to treat alcohol problem has flourished. Naltrexone and acamprosate are tangible fruits of such endeavors and each has now earned approval in a large number of countries. Recent studies on naltrexone indicate that patient compliance is important if full benefits are to be achieved. Several laboratory studies with human subjects are beginning to elucidate the mechanisms underlying efficacy of naltrexone, as well as explaining variability of response among subpopulations of drinkers. In addition to these two agents, recent investigations have also demonstrated that the antidepressants desipramine, imipramine, and fluoxetine reduce mood-related symptoms and, to some extent, drinking itself in alcoholics who are depressed. Research to date suggests that opioid antagonists and selective serotonin reuptake inhibitors are more effective in reducing alcohol intake when used in combination. Clinical issues, methodology, and directions for future research are also reviewed in this article. In particular, issues addressed include alternative dosage regimens, necessary duration of treatment, employment of medications in combination, integration of pharmacologic agents with behavioral interventions, enhancement of patient compliance, and concurrent treatment of psychiatric comorbidity.

Multisite clinical trials have two major advantages over single-site studies: the large sample size of multisite studies allows for adequate statistical power and better representativeness of the population being studied. However, they are more complex to implement than single-site studies. This article reviews previous multisite clinical trials of alcohol abuse and alcoholism, reasons for selecting a multisite design, management of such studies, and some statistical issues.

Sensitivities, specificities, and odds ratios for hazardous drinking for various cut scores on the CAGE are computed for a large sample active duty Army personnel. Contrasts on these properties are made between the standard CAGE and a "modified CAGE" consisting of standard CAGE items and two other items dealing with problematic drinking. The role of demographic variables--gender, ethnicity, marital status, rank category, and age in mediating relationships of both versions of the screening test to hazardous drinking--is also explored. At a cutoff score of one endorsed item, odds ratios were highest for female personnel and commissioned officers. Language: en

Alcoholism is an exceedingly common and serious problem in our society. State-of-the-art estimation procedures place the number of alcohol-dependent persons in the United States at approximately 9 million with an additional 6 million persons diagnosable as nondependent alcohol abusers. Alcohol abuse and alcohol dependence are most prevalent among younger males. For both genders these problems tend to decrease with age (Williams, Grant, Harford, & Noble, 1989).

Pharmacodynamic benefits of disulfiram in the treatment of alcoholism have yet to be clearly demonstrated. Nevertheless, research does suggest that disulfiram may well have positive effects on drinking if medicational compliance procedures are employed. This paper reviews research on four strategies for enhancing disulfiram compliance: implants, incentives, contracts, end patient information. Generalizations about the strategies are drawn and needs for future research are briefly addressed.

The past 10 years have witnessed dramatic growth in alcoholism research. In particular, attention has been focused intensely on techniques that diagnose and treat alcoholism more effectively. The evolution and expansion of this important area is reflected by the fact that in 1990, the National Institute on Alcohol Abuse and Alcoholism, the major funding source for alcoholism research in the world, expended over $22 million on investigations primarily oriented toward treatment issues, whereas the comparable figure a decade earlier was below $2 million. In light of the magnitude as well as the economic and personal cost of alcoholism, public support for research on treatment is likely to be sustained and, in fact, strengthened in the future.

The past decade has witnessed a burgeoning of pharmacotherapy research directed toward the resolution of acute and chronic problems with alcohol. Because of the multifaceted nature of alcohol abuse and alcoholism, a correspondingly wide range of possible medications are being actively investigated, and several show promise in managing the diverse alcohol-related problems that present in clinical practice.(SeeLitten and Allen1for review.)

The past 10 years have witnessed important advances in research on pharmacotherapy for alcoholism. Promising drugs are discussed under six headings: agents to treat alcohol withdrawal; anticraving agents; agents that make drinking an aversive experience; agents to alleviate concomitant psychiatric problems; agents to treat concurrent drug abuse; and amethystic (“sobering-up”) agents. Research on the drug classes is summarized and clinical issues surrounding specific agents and alcoholism pharmacotherapy in general are discussed. Finally, long-range therapeutic implications of recent findings on the actions of alcohol on basic mechanisms of the brain are offered.

Considering the prevalence of excessive alcohol use, its adverse consequences on physical and emotional well-being, and the high degree of responsivity of early-stage drinking problems to brief intervention, screening for alcohol abuse is warranted in medical practice. We describe several practical self-report tests that can help primary care physicians screen their patients for alcohol abuse. Two of the more popular tests, the Michigan Alcoholism Screening Test and the CAGE (an acronym for questions about cutting down on drinking, annoyance at others' concern about drinking, feeling guilty about drinking, and using alcohol as an eye-opener in the morning), are comparable in sensitivity and specificity. Either test is appropriate, but the brevity of CAGE generally gives it an advantage in a busy medical office. Three new tests, the Alcohol Use Disorders Identification Test, the Adolescent Drinking Index, and the TWEAK also are promising. We offer guidelines for selection of screening tests for primary care practice. (Arch Intern Med. 1995;155:1726-1730)

✓ The pituitary function of two patients with acromegaly was monitored before, during, and after selective transnasal pituitary adenomectomy. The purpose of the study was to verify the efficacy of this technique, and to see if there was normal function in the residual pituitary tissue. Following surgery, both patients showed clinical improvement with no evidence of significant anterior or posterior pituitary dysfunction. Concentrations of plasma growth hormone obtained serially during surgery were elevated prior to tumor removal but fell precipitously after adenomectomy. The half-life for immunoreactive growth hormone in these patients was less than 35 minutes. We conclude that selective transnasal pituitary adenomectomy is an effective treatment for pituitary tumors. Furthermore, our data suggest that the pituitary tumor in these patients did not arise because of excessive stimulation by hypothalamic growth hormone-releasing factor.

The alcoholism treatment service delivery system is described in terms of facility characteristics, funding, and demographics of clientele served. A brief discussion of the "Minnesota Model," the most pervasive therapeutic approach to alcoholism in the United States is then offered. The article concludes with a synopsis of key research findings and current public debate issues which may impact the future delivery of treatment services to alcoholics.