Relationship between alcohol intake based on daily smartphone-reported consumption and PEth concentrations in healthy volunteers.

AIMS: To investigate the association between alcohol consumption registered daily with a digital smartphone-based diary and concentration of phosphatidylethanol (PEth) 16:0/18:1 in a population without a known alcohol use disorder (AUD), and evaluate whether prospective registration of alcohol consumption is better than retrospective registration and if the association between alcohol intake and PEth was affected by sex or body mass index (BMI). METHODS: A total of 41 women and 21 men without AUD-diagnosis registered their alcohol consumption prospectively with a digital diary for 14 days, and retrospectively with the Timeline Followback method in the same time interval. PEth was measured before and after the registration period. RESULTS: The correlation between alcohol consumption and PEth varied from 0.65 to 0.87. It did not depend significantly on the reporting method, and was not influenced by sex or BMI. Based on the regression coefficient, a reduction of alcohol consumption by two alcohol units (26 g of pure ethanol) per day would lead to a reduction of the PEth concentration of about 0.1 µmol/l, and vice versa. CONCLUSIONS: There was a good correlation between PEth concentration and alcohol consumption, both when alcohol consumption was reported prospectively and retrospectively. The preferred cut-off for PEth should be adjusted to the level of alcohol consumption considered harmful and a purposeful trade-off between sensitivity and specificity. In order to identify persons with a daily alcohol consumption of more than two or three units of alcohol with a sensitivity of 80% or 90%, we suggest a cut-off of around 0.1 µmol/l.

Validating Self-Reported Unhealthy Alcohol Use With Phosphatidylethanol (PEth) Among Patients With HIV.

BACKGROUND: We sought to compare self-reported alcohol consumption using Timeline Followback (TLFB) to biomarker-based evidence of significant alcohol use (phosphatidylethanol [PEth] > 20 ng/ml). Using data from patients with HIV (PWH) entering a clinical trial, we asked whether TLFB could predict PEth > 20 ng/ml and assessed the magnitude of association between TLFB and PEth level. METHODS: We defined unhealthy alcohol use as any alcohol use in the presence of liver disease, at-risk drinking, or alcohol use disorder. Self-reported alcohol use obtained from TLFB interview was assessed as mean number of drinks/day and number of heavy drinking days over the past 21 days. Dried blood spot samples for PEth were collected at the interview. We used logistic regression to predict PEth > 20 ng/ml and Spearman correlation to quantify the association with PEth, both as a function of TLFB. RESULTS: Among 282 individuals (99% men) in the analytic sample, approximately two-thirds (69%) of individuals had PEth > 20 ng/ml. The proportion with PEth > 20 ng/ml increased with increasing levels of self-reported alcohol use; of the 190 patients with either at-risk drinking or alcohol use disorder based on self-report, 82% had PEth > 20 ng/ml. Discrimination was better with number of drinks per day than heavy drinking days (AUC: 0.80 [95% CI: 0.74 to 0.85] vs. 0.74 [95% CI: 0.68 to 0.80]). The number of drinks per day and PEth were significantly and positively correlated across all levels of alcohol use (Spearman's R ranged from 0.29 to 0.56, all p values < 0.01). CONCLUSIONS: In this sample of PWH entering a clinical trial, mean numbers of drinks per day discriminated individuals with evidence of significant alcohol use by PEth. PEth complements self-report to improve identification of self-reported unhealthy alcohol use among PWH.

Effects of Age, Sex, Body Weight, and Quantity of Alcohol Consumption on Occurrence and Severity of Alcoholic Hepatitis.

BACKGROUND & AIMS: Only a minority of heavy drinking individuals develop alcoholic hepatitis (AH), for unclear reasons. We analyzed data from the Translational Research and Evolving Alcoholic Hepatitis Treatment cohort, consisting of subjects who drink heavily with normal results from liver tests (controls) and patients with AH. We examined risk factors for the development of AH including body mass index (BMI), drinking pattern and quantity, and sex. METHODS: We compared data from 145 patients with AH and 124 controls based on BMI when they joined the cohort; groups were matched for sex and race. Drinking patterns were assessed using the timeline followback method, the Alcohol Use Disorders Identification Test, and the National Institute of Alcohol Abuse and Alcoholism 6-question survey. We performed univariable and multivariable analyses to assess the effects of these factors and their interaction in increasing the risk for AH. We also explored the association between PNPLA3 variants and AH. RESULTS: Cases with AH were older (47 vs 44 y; P = .03). For nearly all measures of quantity of alcohol consumed or frequency of binge drinking, controls drank more heavily than cases with AH. We did not find an association between BMI, sex, drinking patterns, and the presence of AH. Age and BMI were independent predictors for the severity of AH. When we analyzed cases and controls of European ancestry, the PNPLA3 single-nucleotide polymorphism rs738409 was associated with risk for AH (odds ratio, 1.89; P = .007). CONCLUSIONS: Compared with heavy drinkers without liver disease, subjects with AH consumed lower levels of alcohol and had less binge drinking, suggesting an increased sensitivity to the toxic effects of alcohol. The risk for AH may be associated with the PNPLA3 rs738409 polymorphism.

Enhanced cannabis timeline followback (EC-TLFB): Comprehensive assessment of cannabis use including standard THC units and validation through biological measures.

AIMS: The aims of this study were to present an enhanced cannabis timeline followback (EC-TLFB) enabling comprehensive assessment of cannabis use measures, including standard tetrahydrocannabinol (THC) units, and to validate these against objectively indexed urinary 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) concentrations. DESIGN: We used cross-sectional baseline data from the 'CannTeen' observational longitudinal study. SETTING: The study was conducted in London, UK. PARTICIPANTS: A total of 147 participants who used cannabis regularly took part in the study (n = 71 female, n = 76 male; mean age = 21.90, standard deviation = 5.32). MEASUREMENTS: The EC-TLFB was used to calculate frequency of cannabis use, method of administration, including co-administration with tobacco, amount of cannabis used (measured with unaided self-report and also using pictorial aided self-report) and type of cannabis product (flower, hash) which was used to estimate THC concentration (both from published data on THC concentration of products and analysis of cannabis samples donated by participants in this study). We calculated total weekly standard THC units (i.e. 5 mg THC for all cannabis products and methods of administration) using the EC-TLFB. The outcome variable for validation of past week EC-TLFB assessments was creatinine-normalized carboxy-tetrahydrocannabinol (THC-COOH) in urine. FINDINGS: All measures of cannabis exposure included in this analysis were positively correlated with levels of THC-COOH in urine (r = 0.41-0.52). Standard THC units, calculated with average concentrations of THC in cannabis in the UK and unaided self-report measures of amount of cannabis used in grams showed the strongest correlation with THC-COOH in urine (r = 0.52, 95% bias-corrected and accelerated = 0.26-0.70). CONCLUSIONS: The enhanced cannabis timeline followback (EC-TLFB) can provide a valid assessment of a comprehensive set of cannabis use measures including standard tetrahydrocannabinol units as well as and traditional TLFB assessments (e.g. frequency of use and grams of cannabis use).

Feasibility of Ethyl Glucuronide Nail Testing Biomarker for Alcohol Use Among Youth Living With HIV.

PURPOSE: We assessed the feasibility of the ethyl glucuronide biomarker (EtG) through nail sampling to measure alcohol use among youth living with HIV in the United States (YLWH, N = 183); we also evaluated concordance between this EtG biomarker and self-reported measures of alcohol use, specifically, the Alcohol Timeline Followback (TFLB) and Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). METHODS: EtG, TFLB, and ASSIST were collected at 4 points over 1 year. At baseline and 52 weeks, 78.1% and 70.1%, respectively, provided a valid (full or partial) sample. RESULTS: At 16 weeks, EtG was associated with ASSIST (r = .25, p < .05). At 28 weeks and 52 weeks, TFLB and ASSIST were correlated with EtG (at 28 weeks r = .23, p < .05 and r = .41, p < .01, respectively; at 52 weeks r = .34, p < .01 and r = .25, p < .05, respectively). CONCLUSIONS: We found that nail-based EtG biomarker was feasible to measure alcohol use among YLWH; we also found concordance between EtG, TLFB, and ASSIST, supporting ongoing use of self-reported alcohol use measures with YLWH.

Characterization of Early-Stage Alcoholic Liver Disease with Hyperhomocysteinemia and Gut Dysfunction and Associated Immune Response in Alcohol Use Disorder Patients.

Heavy alcohol consumption can cause hyperhomocysteinemia, which could be consequential in the proinflammatory response and worsening of the neurobehavioral domains of alcohol use disorder (AUD), such as alcohol withdrawal. We examined the role of heavy drinking, hyperhomocysteinemia, gut dysfunction and inflammation in early-stage alcoholic liver disease (ALD) in AUD patients. A total of 110 AUD patients without clinical manifestations of liver injury were grouped by the serum homocysteine levels (SHL): normal ≤ 13 µmol/L (Group 1 (Gr.1); n = 80), and elevated > 13 µmol/L (Group 2 (Gr.2), n = 30). A comprehensive metabolic panel, SHL, a nutritional assessment, and drinking history assessed by the timeline followback questionnaire were evaluated. A subset analysis was performed on 47 subjects (Gr.1 n = 27; Gr.2 n = 20) for additional measures: Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score, plasma cytokines (interleukin-1ß (IL-1ß)), gut dysfunction markers (lipopolysaccharide (LPS), and LPS-binding protein (LBP)); 27% of the AUD patients exhibited hyperhomocysteinemia. SHL was significantly associated (p = 0.034) with heavy drinking days (HDD90). Subset analyses showed that the withdrawal ratings were both clinically and statistically (p = 0.033) elevated and significantly associated with hyperhomocysteinemia (p = 0.016) in Gr.2. LBP, IL1-ß, SHL, and HDD90 showed significant cumulative effects (adjusted R2 = 0.627) on withdrawal ratings in Gr.2 subset. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher in all Gr.2 patients; AUROC showed a fair level of true positivity for ALT (0.676), and AST (0.686). Il1-ß, LBP, SHL, and HDD90 showed significant cumulative effects (adjusted R2 = 0.554) on the elevated ALT in Gr.2 subset as well. The gut-brain derived proinflammatory response, patterns of heavy drinking, and hyperhomocysteinemia were closely associated with clinically elevated alcohol withdrawal and elevated liver injury. Hyperhomocysteinemia could have a potential phenotypic marker response indicative of early-stage ALD along with AUD.

Collecting Self-Reported Data on Dating Abuse Perpetration From a Sample of Primarily Black and Hispanic, Urban-Residing, Young Adults: A Comparison of Timeline Followback Interview and Interactive Voice Response Methods.

Dating abuse is a prevalent and consequential public health problem. However, relatively few studies have compared methods of collecting self-report data on dating abuse perpetration. This study compares two data collection methods-(a) the Timeline Followback (TLFB) retrospective reporting method, which makes use of a written calendar to prompt respondents' recall, and (b) an interactive voice response (IVR) system, which is a prospective telephone-based database system that necessitates respondents calling in and entering data using their telephone keypads. We collected 84 days of data on young adult dating abuse perpetration using IVR from a total of 60 respondents. Of these respondents, 41 (68%) completed a TLFB retrospective report pertaining to the same 84-day period after that time period had ended. A greater number of more severe dating abuse perpetration events were reported via the IVR system. Participants who reported any dating abuse perpetration were more likely to report more frequent abuse perpetration via the IVR than the TLFB (i.e., may have minimized the number of times they perpetrated dating abuse on the TLFB). The TLFB method did not result in a tapering off of reported events past the first week as it has in prior studies, but the IVR method did result in a tapering off of reported events after approximately the sixth week. We conclude that using an IVR system for self-reports of dating abuse perpetration may not have substantial advantages over using a TLFB method, but researchers' choice of mode may vary by research question, resources, sample, and setting.

A modified Timeline Followback assessment to capture alcohol exposure in pregnant women: Application in the Safe Passage Study.

Prenatal alcohol exposure (PAE) has been linked to poor pregnancy outcomes, yet there is no recognized standard for PAE assessment, and the specific effects of quantity, frequency, and timing remain largely unknown. The Safe Passage Study was designed to investigate the role of PAE in a continuum of poor peri- and postnatal outcomes. The objective of this manuscript is to describe the rationale for, and feasibility of, modifications to the traditional Timeline Followback (TLFB) for collecting PAE information in a large cohort of pregnant women. Participants from the Northern Plains region (in the United States) and Cape Town, South Africa, were followed prospectively using a modified 30-day TLFB interview, administered up to five times, to obtain detailed PAE information. Required modifications for our population included capturing information regarding sharing, type/brand, container size, and duration, in order to accurately record the amount of alcohol consumed. PAE status was defined for 99.9% of the 11,892 enrolled pregnancies at least once during pregnancy and for 92% across all trimesters. Of 53,823 drinks reported, 98% had all items necessary for standard drink computation. Sharing was reported for 74% of drinks in Cape Town, South Africa and for 10% in the Northern Plains. Compared to referent values from the traditional TLFB, 74% and 67% of drinks had different alcohol-by-volume and container size, respectively. Furthermore, a statistically significant difference was found between the number of containers reported and the number of standard drinks computed, using information from the modified TLFB. This is the first study of this size to wholly encompass all of these changes into a single measure in order to more accurately calculate daily consumption and assess patterns over time. The methods used to collect PAE information and create alcohol exposure measures likely increased the accuracy of standard drinks reported and could be generalized to other populations.

Interviewer-administered TLFB vs. self-administered computerized (A-CASI) drug use frequency questions: a comparison in HIV-infected drug users.

BACKGROUND: Substance use can have major consequences among HIV patients. Interviewer- or self-administered modalities are widely used to measure drug use frequency. This often involves Timeline Follow-Back (TLFB) interviewer-administered measures, or self-administered computerized questions assessing similar information via Audio Computer-Assisted Self Interview (A-CASI). Little is known about agreement between these two modalities on drug use frequency in HIV-infected samples. METHODS: Prior to randomization into a trial of brief interventions to reduce drug use, 240 HIV patients completed a baseline A-CASI assessment battery that included questions on drug use frequency, followed by an interviewer-administered TLFB. Each measure generated number of days patients used their primary drug in the prior 30 days. Agreement between TLFB and A-CASI modalities on days using primary drug was determined using intraclass correlation coefficients (ICC). Regression analysis tested the association of patient characteristics with discrepancies between TLFB and A-CASI modalities. RESULTS: Overall agreement was excellent (ICC=.80), with little variation by primary drug, education, race, current drug treatment, binge drinking or years since HIV diagnosis. Gender, ethnicity (Hispanic vs. non-Hispanic) and age predicted differences in days used (p<0.05); the A-CASI modality reflected more days used than TLFB. CONCLUSIONS: Measures of days used primary drug showed high agreement whether assessed by interviewer-administered TLFB or by questions self-administered via the A-CASI modality. Differences by gender, ethnicity and age suggest some caution in using the TLFB, although additional studies are needed. However, findings generally indicate that studies based on one assessment method or the other can be compared with reasonable confidence.

Comparison of self-reported alcohol use with the alcohol biomarker phosphatidylethanol among young people in northern Tanzania.

BACKGROUND: The one-month Time Line Follow Back calendar (TLFB) and the Alcohol Use Disorders Identification Test (AUDIT) are used to collect self-reported alcohol intake data. We compared these instruments with the alcohol biomarker phosphatidylethanol (PEth) among young-people in northern Tanzania. METHODS: AUDIT and TLFB were applied in a cross-sectional study of 202 young people (18-24 years), who reported using alcohol during the past year (103 male casual labourers; 99 college students). We assayed whole blood for PEth 16:0/18:1, using liquid chromatography-tandem mass spectrometry. RESULTS: For both self-report methods, alcohol consumption was high, particularly among men (e.g. a median of 54 drinks per month in labourers), and about half of male students (48%) reported hazardous or harmful levels of drinking (AUDIT ≥8). Almost half (49%) of participants were PEth-positive (median concentration 0.03µmol/L). There were significant positive correlations between reported total alcohol intake and PEth concentration in males (Spearman's correlation rs=0.65 in college students and rs=0.57 in casual labourers; p<0.001). Self-reported use in the past month was a sensitive marker of having a positive PEth result (≥0.01µmol/L) with 89% of those with a PEth positive result reporting alcohol use, and this was similar in all groups. The proportion of those with AUDIT scores ≥8 and AUDIT-C scores ≥6 among those with a high cut-off positive PEth result (≥0.30µmol/L) ranged between 94 and 100%. CONCLUSION: TLFB and AUDIT are sensitive measures to detect heavy alcohol use among young-people in northern Tanzania. They can be used to identify young people who may benefit from alcohol-focused interventions.