Gregory E. Skipper

Ethyl glucuronide discloses recent covert alcohol use not detected by standard testing in forensic psychiatric inpatients

BACKGROUND Considerable lives and money could be saved if one could detect early stages of lapsing/relapsing behavior in addicted persons (e.g., in safety-sensitive workplaces) and could disclose harmful drinking in social drinkers. Due to the serious public health problem of alcohol use and abuse worldwide, markers of alcohol use have been sought. Both ethyl glucuronide (EtG) and phosphatidyl ethanol (PEth) appear to have high sensitivity and specificity and a time frame of detection that may elucidate alcohol use not detected by standard testing. Our aim was to assess their potential for detecting recent covert alcohol use under controlled conditions. METHODS Thirty-five forensic psychiatric inpatients in a closed ward who had committed a substance-related offense ( section sign 64 StGB), were followed for 12 months. The complete time spectrum of possible alcohol consumption was covered by the complementary use of breath and urinary ethanol (hours), urinary EtG (days), %carbohydrate-deficient transferrin (CDT)/PEth (weeks), and gamma-glutamyltranspeptidase (GGT)/mean corpuscular volume (MCV) (weeks-months). RESULTS Fourteen of the 146 urine samples examined were positive for EtG. In all EtG-positive cases, patients reported alcohol consumption of between 40 and 200 g of ethanol 12-60 hr prior to testing. Urinary and breath ethanol were positive in only one case. In the blood samples, PEth was not positive in any case and %CDT did not exceed the reference value. Isoelectric focusing showed no abnormal Tf subtypes. CONCLUSIONS The findings emphasize the diagnostic and therapeutic usefulness, specificity, and sensitivity of EtG as a marker of recent alcohol use. Such a test is needed in numerous settings, including alcohol and drug treatment (to detect lapse/relapse), in safety-sensitive work settings where use is dangerous or in other settings where use may be inappropriate (e.g., such as driving, workplace, pregnancy, or monitoring physicians or other professionals who are in recovery and working), or for testing other groups (such as children or those with medical problems) where alcohol use would be unhealthy or unsafe. The health, social and socioeconomic benefits arising from the future use of these markers is hard to overestimate.

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.

World Health Organization/International Society for Biomedical Research on Alcoholism study on state and trait markers of alcohol use and dependence: Back to the future

This article summarizes content proceedings of a symposium held at the 2004 International Society for Biomedical Research on Alcoholism Congress in Mannheim, Germany. The chairs were Boris Tabakoff and Friedrich M. Wurst. The presentations were (1) Genetic associations with alcoholism and affective disorders, by Paula Hoffman; (2) Proteomic analysis of blood constituents in alcoholism, by Boris Tabakoff; (3) Contrasts between the responses of GGT and CDT to high alcohol intake, and a test of their combined use, by John Whitfield; (4) Direct ethanol metabolites such as ethyl glucuronide, fatty acid ethyl esters, phosphatidylethanol and ethyl sulfate: a new line of sensitive and specific biomarkers, by Friedrich Martin Wurst; and (5) Genetic studies of alcoholism subtypes in a Han Taiwanese population, by Ru-Band Lu.

Phosphatidylethanol: the potential role in further evaluating low positive urinary ethyl glucuronide and ethyl sulfate results.

BACKGROUND Whereas urinary ethyl glucuronide (EtG) levels above 1,000 ng/ml reflect with a high probability ethanol (EtOH) consumption, levels below this cutoff are difficult to interpret as both extraneous (nonbeverage) EtOH exposure, recent drinking, and more distant high EtOH intake (several days ago) might yield similar results. This might be of particular relevance in medico-legal cases. To overcome this dilemma, phosphatidylethanol (PEth) might be a promising marker, because blood PEth is only positive following significant alcohol use. The aim of our study was therefore to employ PEth as a marker to differentiate between the different conditions. METHODS Subjects included were 252 participants in monitoring with the Alabama Physician Health Program. All subjects testing positive for EtG and/or ethyl sulfate (EtS) who denied drinking after routine supportive confrontation were subject to information about PEth testing. If they still denied drinking, PEth testing was performed and the result communicated. EtG, EtS, and PEth testing was performed in a commercial laboratory using liquid chromatography tandem mass spectrometry methods. RESULTS Of a total of 18 subjects who tested positive for EtG and/or EtS, 10 denied drinking. Of the 7 who denied drinking after PEth explanation, in 5 cases, their claim was supported by a negative PEth result. In 2 cases, a positive PEth result was in contrast to their claim. CONCLUSIONS PEth results in combination with previous low positive EtG/EtS results allow differentiating between innocent/extraneous exposure and drinking. Negative PEth testing following low positive EtG/EtS results helps to further elucidate the findings and support the claim of the patient of recent alcohol abstinence. Positive PEth testing following positive EtG/EtS results confirms recent drinking.

Optimizing heroin-assisted treatment (HAT): Assessment of the contribution of direct ethanol metabolites in identifying hazardous and harmful alcohol use

BACKGROUND Heavy alcohol consumption may accelerate the progression of hepatitis C-related liver disease and/or limit efforts at antiviral treatment in opioid-dependent patients receiving heroin-assisted treatment (HAT). Our study aims to assess alcohol intake among HAT patients by self-reports compared to direct ethanol metabolites. METHOD Fifty-four patients in HAT were recruited from the centre for HAT at the University of Basel, Switzerland. The patients completed the Alcohol Use Disorder Identification Test (AUDIT), a self-report questionnaire on past-week ethanol intake and provided samples for the determination of ethyl glucuronide (UEtG) and ethyl sulphate (UEtS) in urine and of ethyl glucuronide (HEtG) in hair. RESULTS Eighteen patients scored above the AUDIT cut-off levels. Twenty-six patients tested positive for UEtG and 29 for UEtS. HEtG identified ethanol intake of more than 20 g/d in 20 additional cases that did not appear in the AUDIT. Using the total score of the AUDIT, HEtG detected 14 additional cases of relevant alcohol intake. CONCLUSIONS The findings of this study, which is the first assessing alcohol intake in HAT patients using direct ethanol metabolites and self reports, suggest the complementary use of both. Improved detection of hazardous or harmful alcohol consumption in the context of HCV and heroin dependence will allow for earlier intervention in this population. This ultimately will contribute to an improvement in quality of life of patients in HAT. Furthermore, a significant reduction of costs can be achieved through a reduction of complications caused by alcohol intake.

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.

The Physician Health Program: A Replicable Model of Sustained Recovery Management

Physician Health Programs (PHPs) in the USA have evolved over the past 3 decades as models of recovery management. They encourage early referral, sophisticated evaluation, and active long-term monitoring and care management of troubled physicians, especially those with substance-related disorders. There are many benefits to these unique programs. Early detection of potentially impaired physicians not only protects patients but also saves physicians’ careers. Additionally, when addressing these problems clinically, rather than awaiting a crisis necessitating disciplinary action, complex and prolonged legal battles are avoided. PHPs safeguard both patients and physicians, and in the process they have developed one of the most successful models of recovery management. The strongest incentive for early referral is the opportunity for confidential care and advocacy for physicians who cooperate with their PHPs. PHPs have proven successful with reports of 5-year abstinence rates of 79%, return to work rates of 96%, and virtually no evidence of risk or harm to patients from participating physicians. Can the principles used by PHPs be transferred for use by other patients? Compared to other patients with addictions, physicians are an affluent and usually highly motivated group; however, there is evidence that their addictions are as severe as or worse as those of the general population. Certainly their access to drugs of abuse is greater than the general population. Many elements of PHP care management can be transferred, in whole or in part, to others offering the promise of substantial improvements in long-term outcomes.

Prognosis for Emergency Physician with Substance Abuse Recovery: 5-year Outcome Study

Introduction: Emergency physicians (EPs) are reported to have a higher rate of substance use disorder (SUD) than most specialties, although little is known about their prognosis. We examined the outcomes of emergency physician compared to other physicians in the treatment of substance use disorders in Physician Health Programs (PHP). Methods: This study used the dataset from a 5-year, longitudinal, cohort study involving 904 physicians with diagnoses of SUD consecutively admitted to one of 16 state PHPs between 1995 and 2001. We compared 56 EPs to 724 other physicians. Main outcome variables were rates of relapse, successful completion of monitoring, and return to clinical practice. Results: EPs had a higher than expected rate of SUD (odds ratio [OR] 2.7 confidence interval [CI]: 2.1–3.5, p<0.001). Half of each group (49% of EPs and 50% of the others) enrolled in a PHP due to alcohol-related problems. Over a third of each group (38% of EPs and 34% of the others) enrolled due to opioid use. During monitoring by the PHPs, 13% of EPs had at least one positive drug test compared to 22% of the other physicians; however, this difference was not significant (p=0.13). At the end of the 5-year follow-up period, 71% of EPs and 64% of other physicians had completed their contracts and were no longer required to be monitored (OR 1.4 [CI: 0.8-2.6], p = 0.31). The study found that the proportion of EPs (84%) continuing their medical practice was generally as high as that of other physicians (72%) (OR 2.0 [CI: 1.0–4.1], p = 0.06). Conclusion: In the study EPs did very well in the PHPs with an 84% success rate in completion and return to clinical practice at 5 years. Of the 3 outcome variables measured, rates of relapse, successful completion of monitoring, and return to clinical practice, EPs had a high rate of success on all variables compared to the other physician cohort. These data support the conclusion that EM physicians do well following treatment of SUD with monitoring in PHPs and generally return to the practice of emergency medicine.

Cellular Photo Digital Breathalyzer for Monitoring Alcohol Use: A Pilot Study

Background: Monitoring alcohol use is important in numerous situations. Direct ethanol metabolites, such as ethyl glucuronide (EtG), have been shown to be useful tools in detecting alcohol use and documenting abstinence. For very frequent or continuous control of abstinence, they lack practicability. Therefore, devices measuring ethanol itself might be of interest. This pilot study aims at elucidating the usability and accuracy of the cellular photo digital breathalyzer (CPDB) compared to self-reports in a naturalistic setting. Method: 12 social drinkers were included. Subjects used a CPDB 4 times daily, kept diaries of alcohol use and submitted urine for EtG testing over a period of 5 weeks. Results: In total, the 12 subjects reported 84 drinking episodes. 1,609 breath tests were performed and 55 urine EtG tests were collected. Of 84 drinking episodes, CPDB detected 98.8%. The compliance rate for breath testing was 96%. Of the 55 EtG tests submitted, 1 (1.8%) was positive. Conclusions: The data suggest that the CPDB device holds promise in detecting high, moderate, and low alcohol intake. It seems to have advantages compared to biomarkers and other monitoring devices. The preference for CPDB by the participants might explain the high compliance. Further studies including comparison with biomarkers and transdermal devices are needed.

Psychiatrists With Substance Use Disorders: Positive Treatment Outcomes From Physician Health Programs

OBJECTIVE The objective of this study was to compare outcomes of psychiatrists and nonpsychiatrist physicians enrolled in state physician health programs for substance use disorders. METHODS The study used the data set from a five-year, longitudinal cohort study of 904 physicians, including 55 psychiatrists, with diagnoses of substance abuse or dependence consecutively admitted to one of 16 state physician health programs between 1995 and 2001. RESULTS There was a higher proportion of women among psychiatrists than among other physicians, but there were no other significant differences between the cohorts. Five-year outcomes were similar between psychiatrists and the other physicians, with at least 75% of psychiatrists continuing their medical practice after five years of monitoring and treatment. CONCLUSIONS Psychiatrists were not overrepresented compared with other physician groups and had similar clinical outcomes at the five-year follow-up. Physician health programs appeared to be effective treatment programs for psychiatrists with substance use disorders.