Scott H. Stewart

Phosphatidylethanol and alcohol consumption in reproductive age women.

BACKGROUND Fetal alcohol disorders are preventable, but self-reported alcohol consumption can be misleading and impede effective treatment. Biomarkers represent an alternative method for assessing alcohol use, and this study evaluated the relationship between blood phosphatidylethanol (PEth) and alcohol use in a sample of reproductive age women. METHODS Alcohol use was estimated by validated self-report methods in 80 nonpregnant women ages 18 to 35. PEth was measured by a contracted laboratory using a liquid chromatography-tandem mass spectrometry assay. Regression methods appropriate for the distribution of PEth were used to define its relationship to alcohol consumption during the prior 2 weeks and explore the effects of drinking patterns on this association. Receiver operating characteristic analysis was used to estimate the sensitivity of PEth for various drinking levels at 95% specific cutoffs. RESULTS PEth had a positive linear association with grams of alcohol consumed (p < 0.001), and was detectable in 93% of subjects consuming an average of 2 or more drinks per day. The relationship between total alcohol consumption and PEth may be stronger in women with recent heavy drinking days. The relationship between drinking and PEth varied considerably between individuals, and sensitivity for a certain amount of drinking was low at a highly specific cutoff concentration. CONCLUSIONS PEth is a highly sensitive indicator of moderate and heavy alcohol consumption in reproductive age women and may complement the use of self-report alcohol screens when additional objective markers of alcohol use are desirable. However, choosing a highly valid cutoff concentration for PEth to differentiate various levels of alcohol consumption may not be feasible.

Preliminary evaluation of phosphatidylethanol and alcohol consumption in patients with liver disease and hypertension.

AIMS The goal of this preliminary study was to evaluate the relationship between blood phosphatidylethanol (PEth) and recent drinking in patients with liver disease and hypertension. METHODS Twenty-one patients with liver disease and 21 patients with essential hypertension were recruited at an academic medical center. Alcohol consumption was estimated using validated self-report methods, and blood PEth was measured by HPLC-MS/MS at a contracted laboratory. Nonparametric comparisons were made between abstainers/light drinkers, moderate drinkers consuming between 1 and 3 drinks per day, and those drinking above this level. Regression methods were used to estimate the effects of liver disease, gender, and age on the relationship between PEth and alcohol use, and to estimate the strength of the linear relationship between PEth and drinking. RESULTS PEth differed significantly between the three drinking groups (P < 0.001). The relationship between PEth and alcohol did not differ between hypertension and liver disease patients (P = 0.696), nor by gender and age. While there was substantial variability between subjects in the PEth concentration given a similar level of reported drinking, the amount of ethanol consumed was strongly associated with the PEth concentration (P < 0.001). CONCLUSION Results support PEth measurement by HPLC-MS/MS as a promising marker of past 1- to 2-week moderate to heavy alcohol consumption in patients with and without liver disease. PEth appears useful for differentiating abstinence or light drinking from moderate to heavy consumption, but may have limited utility for differentiating moderate from heavy alcohol use.

Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms.

Improved treatment of alcohol dependence is a high priority, including defining subtypes that might respond differently. We evaluated a medication combination of intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol-dependent individuals (44 with low AW and 16 with high AW) were randomized to receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol withdrawal was measured for the first 2 days, and drinking, sleep parameters, and adverse events were monitored during weekly evaluations, along with behavioral counseling sessions. Percent days abstinent (PDA) during treatment and time to first heavy drinking (TFHD) day were primary outcome variables. There was an interaction between the pretreatment AW status and the medication group on PDA (P = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more TFHD if treated with active medications, whereas those in the low AW group had more PDA and more TFHD if treated with placebo. This interaction remained for those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate-deficient transferrin values. In addition, the pattern of response remained up to 8 weeks after treatment. In addition, in those with high AW, greater improvement in AW symptoms was observed in the active medication group compared with the placebo group. These results suggest a differential response to FMZ/GBP treatment, depending on pretreatment AW status that should be taken into account during future treatment trials.

VALIDATION OF BLOOD PHOSPHATIDYLETHANOL AS AN ALCOHOL CONSUMPTION BIOMARKER IN PATIENTS WITH CHRONIC LIVER DISEASE

BACKGROUND Blood phosphatidylethanol (PEth) is a promising biomarker of alcohol consumption. This study was conducted to evaluate its performance in patients with liver disease. METHODS This study included 222 patients with liver disease. Patient-reported alcohol use was obtained as a reference standard, and PEth was measured by tandem mass spectrometry. Receiver operating characteristic (ROC) and contingency table analyses were used to assess the performance of PEth in detecting any drinking and averaging 4 or more drinks daily in the past 30 days. RESULTS At the limit of quantitation (20 ng/ml), PEth was 73% sensitive (95% confidence interval [CI] 65 to 80) and 96% specific (95% CI 92 to 100) for any drinking in the past month. Subjects who drank but had a negative PEth result were mainly light drinkers. Subjects who reported 30-day abstinence but with quantifiable PEth either reported heavy drinking within the past 6 weeks or had data that suggested underreported drinking. At the optimal cutoff concentration of 80 ng/ml, PEth was 91% sensitive (95% CI 82 to 100) and 77% specific (95% CI 70 to 83) for averaging at least 4 drinks daily. CONCLUSIONS PEth is a useful test for detecting alcohol use in patients with liver disease, but cutoff concentrations for heavy drinking will result in misclassification of some moderate to heavy drinkers.

Racial and Ethnic Disparity in Blood Pressure and Cholesterol Measurement

AbstractOBJECTIVE: To evaluate racial and ethnic disparity in blood pressure and cholesterol measurement and to analyze factors associated with any observed disparity. DESIGN: Cross-sectional analysis of the household component of the 1996 Medical Expenditure Panel Survey. PARTICIPANTS: Representative sample of the U.S. non-institutionalized population age 21 or older. MEASUREMENTS: Prevalence of self-reported blood pressure measurement within 2 years and cholesterol measurement within 5 years were calculated by race/ethnicity. Logistic regression was used to adjust for health insurance status, having a usual source of care, health status, and socioeconomic and demographic factors. Odds ratios and 95% confidence intervals (95% CIs) from the logistic regression were converted to prevalence ratios to estimate relative risk (RR). MAIN RESULTS: Mexican Americans compared to non-Hispanic whites were less likely to have a blood pressure measurement (RR, 0.85; 95% CI, 0.81 to 0.89) or a cholesterol measurement (RR, 0.72; 95% CI, 0.65 to 0.78). Non-Hispanic blacks had blood pressure and cholesterol measurements similar to non-Hispanic whites. In a multivariate analysis, Mexican Americans had similar blood pressure measurements (RR, 0.97; 95% CI, 0.94 to 1.00) and cholesterol measurements (RR, 1.04; 95% CI, 0.99 to 1.08). The factors associated with the largest disparity were lack of health insurance, not having a usual source of care, and low education. CONCLUSIONS: No disparity was found between non-Hispanic blacks and non-Hispanic whites in undergoing blood pressure and cholesterol measurement. Disparities in cardiovascular preventive services for Mexican Americans were associated with lack of health insurance and a usual source of care, but other demographic and socioeconomic factors were also important.

Medical Treatment of Alcohol Dependence: A Systematic Review

Objective: To summarize published data on pharmacologic treatments for alcohol dependence alone and in combination with brief psychosocial therapies that may be feasible for primary care and specialty medical settings. Methods: We conducted electronic searches of published original research articles and reviews in MEDLINE, SCOPUS, CINAHL, Embase, and PsychINFO. In addition, hand searches of reference lists of review articles, supplemental searches of internet references and contacts with experts in the field were conducted. Randomized controlled studies published between January 1960 and August 2010 that met our inclusion/exclusion criteria were included. Results: A total of 85 studies, representing 18,937 subjects, met our criteria for inclusion. The evidence base for oral naltrexone (6% more days abstinent than placebo in the largest study) and topiramate (prescribed off-label) (e.g., 26.2% more days abstinent than placebo in a recent study) is positive but modest. Acamprosate shows modest efficacy with recently abstinent patients, with European studies showing better results than U.S. ones. The evidence-base for disulfiram is equivocal. Depot naltrexone shows efficacy (25% greater reduction in rate of heavy drinking vs. placebo, in one of the largest studies) in a limited number of studies. Some studies suggest that patients do better with extensive psychosocial treatments added to medications while others show that brief support can be equally effective. Conclusions: Although treatment effects are modest, medications for alcohol dependence, in conjunction with either brief support or more extensive psychosocial therapy, can be effective in primary and specialty care medical settings.

SENSITIVITY AND SPECIFICITY OF URINARY ETHYL GLUCURONIDE AND ETHYL SULFATE IN LIVER DISEASE PATIENTS

BACKGROUND It is important to monitor alcohol use in the care of patients with liver disease, but patient self-report can be unreliable. We therefore evaluated the performance of urine ethyl glucuronide (EtG) and ethyl sulfate (EtS) in detecting alcohol use in the days preceding a clinical encounter. METHODS Subjects (n = 120) were recruited at a university-based hepatology clinic or during hospitalization. Alcohol consumption was ascertained by validated self-report measures. Urine EtG (cutoff 100 ng/ml) and EtS (cutoff 25 ng/ml) concentrations were assayed by a contracted laboratory using tandem mass spectrometry. The sensitivity and specificity of each biomarker in the detection of drinking during the 3 and 7 days preceding the clinic visit were determined, as well as the influence of liver disease severity on these results. RESULTS Urine EtG (sensitivity 76%, specificity 93%) and urine EtS (sensitivity 82%, specificity 86%) performed well in identifying recent drinking, and liver disease severity does not affect biomarker performance. After elimination of 1 false-negative self-report, urine EtG > 100 ng/ml was 100% specific for drinking within the past week, whereas 9% of the subjects without evidence of alcohol drinking for at least 1 week had EtS > 25 ng/ml. CONCLUSIONS Urine EtG and EtS can objectively supplement the detection of recent alcohol use in patients with liver disease. Additional research may determine optimal methods for integrating these tests into clinical care.

Blood pressure reduction during treatment for alcohol dependence: results from the Combining Medications and Behavioral Interventions for Alcoholism (COMBINE) study.

AIMS Heavy drinking is associated with hypertension. This study evaluated blood pressure changes occurring during treatment for alcohol dependence. PARTICIPANTS Subjects included 1383 people participating in the Combining Medications and Behavioral Interventions for Alcoholism (COMBINE) study, a large multi-center treatment study for alcohol dependence. MEASUREMENTS Methods appropriate for repeated-measures data were used to assess the relationship of percentage of drinking days (PDD) to systolic and diastolic blood pressure over a 16-week treatment period. Modification of these associations by demographic and other variables was assessed. FINDINGS Blood pressure reduction was evident only in people who were above the median blood pressure at baseline. In this group, systolic blood pressure decreased by an average of 12 mmHg and diastolic blood pressure decreased by an average of 8 mmHg. Blood pressure reduction occurred during the first month of treatment. This effect was similar regardless of age, sex, body mass index, reported history of hypertension and use of anti-hypertensive medications. An observed association between blood pressure and PDD in Caucasians was not evident in African Americans due largely to their lower pre-treatment blood pressure. CONCLUSIONS Reduction in alcohol consumption has a potent anti-hypertensive effect in alcoholics with higher blood pressure. For hypertensive, alcohol-dependent people, treatment for alcoholism should be considered a major component of anti-hypertensive therapy.

Liver Disease and HPLC Quantification of Disialotransferrin for Heavy Alcohol Use: A Case Series

BACKGROUND It had previously been suggested that individuals with cirrhosis may have a pattern of transferrin glycosylation that interferes with the interpretation of carbohydrate-deficient transferrin (CDT) testing for heavy alcohol use. The goal of this case series was to evaluate the prevalence of liver disease among individuals with poor resolution of transferrin glycoforms by high performance liquid chromatography. METHODS We reviewed the electronic medical records of 35 consecutive patients with poor chromatographic resolution of disialotransferrin from trisialotransferrin and recorded information on diagnosed liver disease, liver function testing, and other factors. RESULTS Thirty of the 35 subjects with poor chromatographic resolution of the transferrin glycoforms had sufficient data in the medical record for some estimation of liver function. Of these 30 subjects, 25 had previously diagnosed liver pathology. Of the remaining 5 subjects, 2 had liver imaging results suggestive of benign tumor; the remaining 3 had mildly elevated bilirubin and aminotransferase activity, and low albumin. CONCLUSIONS Liver abnormalities, but not necessarily cirrhosis, are common in individuals with poor chromatographic separation of transferrin glycoforms, which might lead to false-positive results on CDT testing. However, the chromatographic-based assay can detect this issue, minimizing the reporting of false positives, but not necessarily assisting in valid detection of heavy drinking.

PREVALENCE OF PROBLEM DRINKING AND CHARACTERISTICS OF A SINGLE-QUESTION SCREEN

Hazardous drinking and alcohol use disorders (i.e, abuse and dependence) are common in Emergency Departments (EDs). This study examined 1) the prevalence of these conditions among ED patients and 2) characteristics of a single screening question (having consumed at least five drinks for males or four for females during a single day). Data from the National Epidemiologic Survey on Alcohol and Related Conditions were analyzed. Logistic regression for clustered data was used to estimate the relative risk for past-year ED use associated with hazardous drinking, abuse, and dependence. Contingency tables were analyzed to estimate the sensitivity and specificity of the single-question screen for detecting these conditions. Hazardous drinking was not associated with ED utilization. Alcohol abuse was associated with a relative risk of 1.3 (95% confidence interval [CI] 1.1-1.5) and alcohol dependence with a relative risk of 1.9 (95% CI 1.6-2.2). For current drinkers, the single question screen was 0.96, 0.85, and 0.90 sensitive for hazardous drinking, alcohol abuse, and alcohol dependence, respectively. Individuals with a positive screen in the past year were considered at least hazardous drinkers, and specificity was 0.80, 0.64, and 0.65 for hazardous drinking, abuse, and dependence, respectively. Specificity was modestly increased in women. Most problem drinkers were hazardous drinkers, but only severe alcohol use disorders were particularly prevalent in the ED. The single heavy-drinking-day item appears sensitive for problem drinking. Positive tests must be followed by additional assessment to differentiate hazardous drinking from alcohol use disorders.