The inter-play between facilitation and context in the promoting action on research implementation in health services framework: A qualitative exploratory implementation study embedded in a cluster randomized controlled trial to reduce restraint in nursing homes.

AIM: To explore the inter-play between external facilitation and nursing home contexts relative to intervention outcomes. BACKGROUND: The Promoting Action on Research Implementation in Health Services framework is frequently used to theoretically inform implementation and research in nursing and recent reviews indicate high face validity for health services. However, the inter-play and relationship between framework sub-elements of evidence, context and facilitation and the prospective utility in non-English speaking contexts warrant further illumination. DESIGN: In an overarching single-blind cluster-randomized controlled trial, we applied participatory action research and ethnography from August 2011-June 2015 to evaluate a standardized education intervention to reduce restraint and agitation in nursing home residents living with dementia. The trial results are published elsewhere. METHODS: Prospectively informed by the PARIHS framework, a research team and eight facilitators participating in dual roles as action researchers designed, implemented, and evaluated the intervention. How contextual factors influenced the facilitation processes were explored in focus group interviews (1), reflection notes (84) written by the facilitators' after each education session, ethnographic field studies (6 homes), and co-analysis workshops (5). Directed content analysis was used to analyse data. RESULTS: Clinical leaders taking roles of internal facilitator influenced the success of implementation, while complex and fluctuating context elements determined whether restraint use was reduced- or not. The PARIHS framework was found to be relevant in a non-English nursing home setting, albeit some elements merit further conceptualization. CONCLUSIONS: Our findings confirm the prospective utility of the PARIHS framework for implementation in a non-English context, particularly the notion of implementation processes as dynamic and multifaceted.

Urinary ethyl glucuronide and ethyl sulfate testing for recent drinking in alcohol-dependent outpatients treated with acamprosate or placebo.

AIMS: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are sensitive and specific biomarkers for recent alcohol ingestion. This study compared urinary EtG and EtS measurement with self-reports for detection of prior drinking in alcohol-dependent outpatients treated with the anti-craving medication acamprosate or placebo. METHODS: Alcohol-dependent outpatients (26 women, 30 men) were randomized to 21 days of oral acamprosate (2 g/day) or placebo treatment in a double-blind design. They were instructed to refrain from drinking during the study. Return visits to the ward for blood and urine sampling and filling out questionnaires were made on Day 7, 14 (urine sample optional) and 22 (urine sample mandatory). EtG and EtS were determined by liquid chromatography-mass spectrometry. RESULTS: On the first day (Day 0), 72% of all patients (acamprosate 65%, placebo 78%) tested positive for recent drinking according to urinary EtG (reporting limit ≥ 0.5 mg/l) and EtS (≥ 0.1 mg/l). On the final day (Day 22), the frequency of positive tests was significantly reduced to 30% in the acamprosate group (P = 0.0374) and 33% for placebo (P = 0.0050). However, there was no difference between the treatment groups. When both groups were combined, the EtG (P = 0.025) and EtS (P = 0.015) concentrations were lower on the final day. Altogether, EtG and EtS were detected in 76 of 156 (49%) urine samples. When drinking in the day before sampling was admitted, 93% of urines tested positive; when drinking was denied, still 28% of the samples were positive. CONCLUSION: These results confirmed the value of urinary EtG and EtS as reliable indicators of recent drinking during outpatient treatment of persons with alcohol-related problems, and as objective outcome measures when evaluating new alcohol treatment strategies and pharmacotherapies.

Urinary ethyl glucuronide and ethyl sulfate testing for detection of recent drinking in an outpatient treatment program for alcohol and drug dependence.

AIMS: This study determined the information about recent alcohol consumption obtained when urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) were introduced as a routine test in outpatient treatment programs for alcohol and drug dependence. PATIENTS AND METHODS: Outpatients (21 men and 3 women) undergoing treatment for alcohol (N = 8) or drug (N = 10) dependence, or in methadone maintenance therapy (N = 6) volunteered for the study. Twice weekly in connection with return visits to the unit, patients gave a urine sample and completed an anonymous single-question form about any drinking in the past 3 days. Urinary EtG and EtS were determined by liquid chromatography-mass spectrometry. RESULTS: Totally, 214 urine samples (4-14 samples/patient; mean 9) and 211 self-reports were collected over a 2-8-week period. Altogether 26% of the urine samples from 12 of 24 patients tested positive for EtG (0.5-434 mg/l) and/or EtS (0.1-87 mg/l). In one patient, samples were only positive for EtS. In 21% of 211 self-reports from 11 patients, alcohol ingestion was admitted in the past 3 days. In 87% of the 211 complete cases, the self-report information agreed with the EtG/EtS results (i.e. true positives and true negatives). The highest frequency of drinking was seen in the drug-dependent group with only 20% of the patients being abstinent according to both measures. This compares with 62.5% abstinence in the alcohol-dependent group and 50% in the methadone maintenance therapy group. CONCLUSION: Although based on a limited number of subjects, these results indicated that urinary EtG and EtS testing is a useful tool for objective identification of recent drinking in outpatients treated for alcohol and drug dependence.

Value of ethyl glucuronide in plasma as a biomarker for recent alcohol consumption in the emergency room.

AIM: This emergency department (ED) study compared the value of plasma ethyl glucuronide (EtG) testing with the information about alcohol consumption obtained using the standard alcohol biomarkers gamma-glutamyltransferase (GGT) and carbohydrate-deficient transferring (CDT) and the AUDIT questionnaire. METHODS: Minimally injured and clinically non-intoxicated male patients (n = 81) admitted to an ED were screened regarding their alcohol consumption, using the computerized AUDIT questionnaire and a paper-and-pencil assessment including the type, amount and time of alcohol intake. Blood samples were collected for determination of ethanol, EtG (LC-MS) and GGT in plasma and %CDT in serum (Axis-Shield %CDT immunoassay). RESULTS: Out of the 81 patients, 23 (28%) were positive (>/=8 points) on the AUDIT questionnaire. Only 3 (4%) showed a detectable ethanol concentration (range 0.01-0.07 g/L) but 31 (38%) showed a detectable EtG (0.16-39.5 mg/L). In four patients, EtG was detectable in plasma for >48 h after estimated completed elimination of ethanol. EtG was not correlated with the long-term biomarkers %CDT or GGT, or the AUDIT results, but with the time since estimated completed ethanol elimination. CONCLUSION: EtG testing in blood was found useful in the ED as a way to detect recent drinking, even in cases of a negative ethanol test, and to confirm abstinence from alcohol. This sensitive and specific short-term biomarker provides valuable additional information about individual drinking habits and might also be helpful to identify an alcohol hangover.

Postcollection synthesis of ethyl glucuronide by bacteria in urine may cause false identification of alcohol consumption.

BACKGROUND: Ethyl glucuronide (EtG) is a minor ethanol metabolite used as a specific marker to document recent alcohol consumption; confirm abstinence in treatment programs, workplaces, and schools; and provide legal proof of drinking. This study examined if bacterial pathogens in urine may enable postsampling synthesis of EtG and ethyl sulfate (EtS) from ethanol, leading to clinical false-positive results. METHODS: Urine specimens with confirmed growth of Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae were stored at room temperature in the presence of ethanol. Ethanol was either added to the samples or generated by inoculation with the fermenting yeast species Candida albicans and glucose as substrate. EtG and EtS were measured by LC-MS. RESULTS: High concentrations of EtG (24-h range 0.5-17.6 mg/L) were produced during storage in 35% of E. coli-infected urines containing ethanol. In some specimens that were initially EtG positive because of recent alcohol consumption, EtG was also sensitive to degradation by bacterial hydrolysis. In contrast, EtS was completely stable under these conditions. CONCLUSIONS: The presence of EtG in urine is not a unique indicator of recent drinking, but might originate from postcollection synthesis if specimens are infected with E. coli and contain ethanol. Given the associated risks for false identification of alcohol consumption and false-negative EtG results due to bacterial degradation, we recommend that measurement of EtG be combined with EtS, or in the future possibly replaced by EtS.

Determination of urinary 5-hydroxytryptophol glucuronide by liquid chromatography-mass spectrometry.

5-Hydroxytryptophol glucuronide (GTOL) is the major excretion form of 5-hydroxytryptophol (5-HTOL), a minor serotonin metabolite under normal conditions. Because the concentration of 5-HTOL is markedly increased following consumption of alcohol, measurement of 5-HTOL is used as a sensitive biomarker for detection of recent alcohol intake. This study describes the development and evaluation of a liquid chromatography-electrospray ionization mass spectrometry (LC-MS) procedure for direct quantification of GTOL in human urine. Deuterium labelled GTOL (GTOL-(2)H(4)) was used as internal standard. GTOL was isolated from urine by solid-phase extraction on a C(18) cartridge prior to injection onto a gradient eluted Hypurity C(18) reversed-phase HPLC column. The detection limit of the method was 2.0 nmol/L and the measuring range 6-8500 nmol/L. The intra- and inter-assay coefficients of variation were <3.5% (n=10) and <6.0% (n=9), respectively. The new LC-MS method was highly correlated with an established GC-MS method for urinary 5-HTOL (r(2)=0.99, n=70; mean 5-HTOL/GTOL ratio=1.10). This is the first direct assay for quantification of GTOL in urine. The method is suitable for routine application.

Urinary ethyl glucuronide and 5-hydroxytryptophol levels during repeated ethanol ingestion in healthy human subjects.

AIMS: This study investigated the stability and reproducibility of urinary ethyl glucuronide (EtG) and the 5-hydroxytryptophol (5-HTOL) to 5-hydroxyindole-3-acetic acid (5-HIAA) ratio, both of which are used as biochemical markers of recent alcohol consumption, after single and multiple oral doses of ethanol in healthy human subjects. METHODS: Nine females aged 19-27 years drank ethanol (8%, w/v, in juice) or placebo (juice) in random order. The intervention consisted of 0.4 g/kg (22-28 g) of ethanol or placebo twice daily (in the morning and evening) during 8 consecutive days, starting in the evening on day 1. Spot urine samples of the first morning void were collected during the 8-day drinking period and for another 3 days (days 9-11) with no intake of ethanol or placebo. Ethanol, EtG, 5-HTOL and 5-HIAA were determined in the urine samples by headspace GC, LC-MS, GC-MS and HPLC, respectively. RESULTS: The individual results during the drinking period were highly variable, both within and between subjects, ranging from 0-7.3 mmol/l for ethanol, 1.4-71.0 mg/l for EtG, 0.1-4.5 mg/mmol for the EtG/creatinine ratio, and 2-109 nmol/ micro mol for 5-HTOL/5-HIAA. The placebo group consistently showed negative values for ethanol (< 0.1 mmol/l) and 5-HTOL/5-HIAA (< 15 nmol/ micro mol), but two samples were positive for EtG (> 0.1 mg/l). In the morning of day 9 (i.e. approximately 14-15 h after the last dose), ethanol was no longer measurable in urine and the 5-HTOL/5-HIAA ratio had returned to below the reference value, but detectable levels of EtG (11.3 +/- 6.0 mg/l, mean +/- SD) and the EtG/creatinine ratio (1.0 +/- 0.3 mg/mmol) were found in all samples. CONCLUSIONS: The results confirm the increase in urinary EtG and 5-HTOL levels during acute ethanol intake, although the individual values were highly variable both within and between subjects. No significant accumulation of either compound occurred upon multiple-dose administration of 0.8 g/kg (44-57 g) ethanol per day for approximately 1 week.

Direct quantification of ethyl glucuronide in clinical urine samples by liquid chromatography-mass spectrometry.

Ethyl glucuronide is a minor metabolite of ethanol, and its presence in urine can be used as a laboratory test to detect recent alcohol intake, even for some time after the ethanol is no longer measurable. A simple analytical procedure was developed based on direct injection of urine diluted with a deuterated internal standard into an electrospray liquid chromatographic-mass spectrometric (LC-MS) system. A novel LC system using a porous graphite column (Hypercarb) enabled an isocratic elution with retention times of 5-6 minutes. The intra- and inter-assay coefficients of variation were 2-12%, and the measuring range was 0.1-1,500 mg/L (0.45-6,750 micromol/L). Ethyl glucuronide was found to be stable in urine for more than 4 days at room temperature, and no artifactual formation was observed on storage of urine samples fortified with 1% ethanol. Ethyl glucuronide was not detected in urine samples collected after abstinence from alcohol. Intake of a very low amount (7 g) of ethanol produced ethyl glucuronide values up to 8.4 mg/L after 4 hours and was still detectable at 6 hours. When the method was applied for routine screening of 252 clinical urine samples (range, 0-1,240 mg/L), it fulfilled the need for a simple and reliable assay to be used in the evaluation of urinary ethyl glucuronide as a routine test of recent alcohol intake.

Comparison of urinary excretion characteristics of ethanol and ethyl glucuronide.

This study compared the urinary excretion characteristics of ethyl glucuronide (EtG) with that of ethanol, with focus on the effect of water-induced diuresis. Six healthy volunteers ingested an ethanol dose of 0.5 g/kg (range 25.0-41.5 g) as 5% (v/v) beer in 30 min and the same volume of water after 3 h. Urine collections were made before starting the experiment and at timed intervals over 31.5 h. The concentration of EtG was determined by an LC-MS method (LOQ = 0.1 mg/L). The urine samples collected immediately before starting drinking were all negative for ethanol and EtG, thus confirming that the participants had not recently ingested alcohol. Intake of beer resulted in a marked increase in excreted urine volume and a concomitant drop in creatinine concentration. The concentration of ethanol peaked at a mean value of 17 mmol/L in the 1.5-h urine collection. Except for one subject, EtG was first detectable (range 0.9-5.5 mg/L) at 1 h. Intake of water at 3 h produced another increase in urine volume and a drop in creatinine. The ethanol concentration curve was not influenced by the water diuresis, whereas this caused a distinct drop in the EtG concentration. When EtG was expressed relative to the creatinine value, this ratio was seemingly not affected by the intake of water. The ethanol concentration returned to zero at 6.5 h, whereas EtG was still detectable for up to 22.5-31.5 h, albeit at low levels in the end (< 1 mg/l). Only about 0.02% of the administered dose of ethanol (on a molar basis) was recovered in the urine as EtG. The results demonstrated that EtG remains detectable in the urine for many hours after the ethanol itself has been eliminated. Moreover, it was possible to lower the concentration of EtG by drinking large amounts of water prior to voiding, whereas this strategy did not influence the EtG/creatinine ratio or the concentration of ethanol.