Provider reasons for discontinuing long-term opioid therapy following aberrant urine drug tests differ based on the type of substance identified.

OBJECTIVE: Urine drug testing (UDT) is increasingly performed as a means of identifying aberrant behavior that may be grounds for discontinuation of long-term opioid therapy (LTOT). Little is known, however, about the ways in which positive UDT results may differentially inform decisions to discontinue LTOT based on the type of substance for which the UDT screened positive. The aim of this study was to examine the likelihood of clinician-initiated discontinuation of LTOT attributed to positive UDT results across three discrete categories of substances: (1) cannabis, (2) alcohol or illicit substances (excluding cannabis), and (3) controlled prescription medications that were not prescribed. DESIGN: This retrospective study utilized the US Department of Veterans Affairs (VA) Health Care System. Corporate Data Warehouse to assemble a sample of 600 patients with substance use disorders and matched controls who were discontinued from LTOT in 2012. Comprehensive manual medical record review identified UDT results in the year prior to discontinuation and reason(s) for discontinuation. PATIENTS, PARTICIPANTS: Patients with one or more UDTs positive for a single substance (N = 185) comprised the study sample. MAIN OUTCOME MEASURE(S): Likelihood of clinician-initiated discontinuation attributed to a positive UDT across the three categories. RESULTS: Patients with one or more UDTs positive for cannabis were more likely to be discontinued from opioid therapy as a result of the positive UDT compared to those with one or more UDTs positive for nonprescribed prescription medication (adjusted odds ratio [OR] = 18.05, 95% CI = 7.29-44.66). Similarly, patients with UDTs positive for alcohol or illicit substances were more likely to be discontinued for the positive UDTs relative to patients who tested positive for nonprescribed prescription medications (adjusted OR = 13.10, 95% CI = 4.81-35.68). No difference in UDT-related discontinuation decisions was evident between patients with UDTs positive for alcohol/illicit substances versus cannabis (adjusted OR = 1.47, 95% CI = 0.57-3.77). CONCLUSIONS: High odds of UDT-related discontinuation were found in patients who tested positive for cannabis, alcohol, or illicit substances, relative to nonprescribed prescription medications.

(1)H-NMR based metabolomics study for the detection of the human urine metabolic profile effects of Origanum dictamnus tea ingestion.

(1)H NMR spectroscopy was employed to investigate the repercussion of Origanum dictamnus tea ingestion in several volunteers' urine metabolic profiles, among them two with chronic inflammatory bowel diseases (IBD), mild IBD and Crohn's disease. Herein, we demonstrate that the concentrations of a lot of urinary metabolites such as hippurate, trimethylamine oxide (TMAO), citrate, and creatinine are altered, which prompts the intestinal microflora function/content perturbation as well as kidney function regulation by dictamnus tea. Interestingly, our preliminary results showed that a high dose of dictamnus tea intake appeared to be toxic for a person with Crohn's disease, since it caused high endogenous ethanol excretion in urine. All subjects' metabolic effects caused by the dictamnus tea appeared to be reversible, when all volunteers stopped its consumption. Finally, we highlight that individuals' metabolic phenotype is reflected in their urine biofluid before and after the dictamnus tea effect while all individuals have some common and different metabolic responses to this tea, implying that each phenotype has a quite different response to this tea consumption.

Urinary NMR-based metabolomic analysis of rats possessing variable sperm count following orally administered Eurycoma longifolia extracts of different quassinoid levels.

ETHNOPHARMACOLOGICAL RELEVANCE: Eurycoma longifolia (Tongkat Ali, TA) roots have been ethnically used as a remedy to boost male sexual desire, libido, energy and fertility. AIM OF THE STUDY: The study evaluated the effect of TA extracts with different quassinoid levels on rats sperm count and examined corresponding post-treatment urinary metabolic changes. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats, categorized into 4 groups of 6 rats each, were orally administered for 48 days with water for the control (group 1), 125mg/kg of TA water extract (TAW, group 2), 125mg/kg of TA quassinoid-poor extract (TAQP, group 3) and 21mg/kg of TA quassinoid-rich extract (TAQR, group 4). Upon completion of the 48-day treatment, the urine samples were analyzed by NMR and the animals were subsequently sacrificed for sperm count analysis. The urine profiles were categorized according to sperm count level. RESULTS: The results showed that the sperm count in TAW- and TAQR-treated groups was significantly higher compared to the TAQP-administered and control groups. The orthogonal partial least squares discriminant analysis (OPLS-DA) model indicated a clear separation among the urine profiles with respect to sperm count level. Urine (1)H-NMR profiles of the high-sperm count group contained higher concentrations of trigonelline, alanine, benzoic acid and higher intensity of a signal at 3.42ppm, while ethanol was at higher concentration in the normal-sperm count group. CONCLUSIONS: The results proved the efficacy of quassinoids on sperm count increase in rats and provided quantitative markers in urine suitable for analysis of sperm profile and male fertility status.

[Simulation of parameters of alcohol-oxidizing enzyme systems and pathomorphological characteristics in situations of acute ethanol poisoning and ischemic heart disease].

Morphometric characteristics and forensic chemical information used in diagnostics of acute ethanol intoxication and coronary heart disease in conjunction with macro- and microscopic pathomorphological signs of the changes in the heart, liver, and kidneys provide data that may suggest the presence of pathology but do not permit to reliably identify it. In this context, evaluation of activities of alcohol-oxidizing enzyme systems acquires clinical significance. The analysis of correlations between quantitative parameters supplemented by the construction of binary models allows to objectively interpret the conclusions about the cause of death in each concrete case of acute ethanol poisoning and coronary heart disease.

Medium-chain triglycerides inhibit free radical formation and TNF-alpha production in rats given enteral ethanol.

This study determined whether free radical formation by the liver, tumor necrosis factor (TNF)-alpha production by isolated Kupffer cells, and plasma endotoxin are affected by dietary saturated fat. Rats were fed enteral ethanol and corn oil (E-CO) or medium-chain triglycerides (E-MCT) and control rats received corn oil (C-CO) or medium-chain triglycerides (C-MCT) for 2 wk. E-CO rats developed moderate fatty infiltration and slight inflammation; however, E-MCT prevented liver injury. Serum aspartate aminotransferase levels, gut permeability, and plasma endotoxin doubled with E-CO but were blunted approximately 50% with E-MCT. In Kupffer cells from E-CO rats, intracellular calcium was elevated by lipopolysaccharide (LPS) in a dose-dependent manner. In cells from E-MCT rats, increases were blunted by approximately 40-50% at all concentrations of LPS. The LPS-induced increase in TNF-alpha production by Kupffer cells was dose dependent and was blunted by 40% by MCT. E-CO increased radical adducts and was reduced approximately 50% by MCT. MCT prevent early alcohol-induced liver injury, in part, by inhibition of free radical formation and TNF-alpha production by inhibition of endotoxin-mediated activation of Kupffer cells.

Increasing employment of opioid dependent outpatients: an intensive behavioral intervention.

The impact of a new, mandatory employment requirement in a community-based methadone treatment program was evaluated. All patients who had been in the methadone substitution program for at least 1 year but who were not currently employed (n = 36) were required to enhance their treatment with 20 h of employment (paid or volunteer). Patients with significant psychiatric or medical disabilities were excluded from the routine treatment requirement. Patients were informed by counseling staff that they had 2 months to secure employment. Those who did not accomplish the goal within that time period were transferred to more intensive weekly counseling (i.e. up to 8 h/week) for 10 weeks, with the enhanced counseling focusing primarily on resistance to the employment goal. Patients who remained resistant to the treatment plan were eventually started on a 21 day methadone taper until employment was verified. Seventy-five percent of the patients secured employment and maintained the position for at least 1 month. Positions were found in an average of 60 days. Most patients (78%) continued working throughout the 6-month follow-up. Those who failed to find work or maintain employment engaged in more illicit drug use. These results demonstrate that behavioral contingencies can motivate many methadone maintenance patients to obtain verified employment in the community.

The confirmation of volatiles by solid-phase microextraction and GC-MS in the investigation of two traffic fatalities.

A simple, sensitive, and reliable method was developed for the confirmation of nonroutine volatiles in the investigation of two traffic fatalities. Solid-phase microextraction (SPME) fibers were used to extract volatile compounds from the headspace of sample vials; components were subsequently analyzed by gas chromatography-mass spectrometry (GC-MS). In the first case, ethanol and methylene chloride were detected in a urine sample by headspace SPME and GC-MS. The second case involved the analysis of volatile petroleum products from submitted specimens by headspace SPME and GC-MS. In both cases, SPME and GC-MS analyses provided crucial evidence in the investigation of the traffic fatalities.

A review of patients on methadone maintenance.

This study involves a review of 178 patients on a strictly monitored methadone maintenance programme. All patients had a minimum of 9 years of intravenous drug misuse. 35.7% were HIV positive, 55.7% males and 29% females had previous prison sentences. On average patients had undergone 3.26 out-patient and 0.9 in-patient detoxification. 46.1% had attempted rehabilitation in the past. Out of 25,470 urine samples obtained while on the programme, 10.8% were positive for opiates, 19.2% for benzodiazepines, 32.5% for cannabis, 4.92% for alcohol and 2.27% for amphetamines. Long history of misuse, multiple custodial sentences, previous unsuccessful rehabilitation and positive HIV status were associated with acceptance for maintenance. Frequency of urinalysis, and results triggering dose change can effectively reduce illicit drug use.

Alcohol hangover and Liv.52.

Ethanol and acetaldehyde levels in blood and urine have been evaluated in 9 volunteers following administration of Liv.52 and placebo on the evening of the study and on the following morning. On the following morning the volunteers scored their symptoms and completed visual analogue scales. Single dose and multiple dose studies were done. Liv.52 produced a considerable reduction in blood and urine levels of ethanol and acetaldehyde after 12 h. It is possible that Liv.52 prevents the binding of acetaldehyde, bringing about higher initial blood levels followed by rapid elimination. It reduced the hangover symptoms.

Acute ethanol ingestion by humans and subacute treatment of rats increase urinary folate excretion.

Previous studies with rats showed that acute treatment with ethanol (4 g/kg) produce a marked increase in urinary folate levels, followed by a decrease in plasma folate levels. Analogous studies with human volunteer subjects using a lower dose of ethanol showed that there were small, but statistically significant increases in urinary folate levels after four hours. The initial ethanol dose was 1.0 g/kg with a single supplement of 0.1-0.2 g/kg to maintain ethanol blood levels at about 100 mg/dl for six hours. Further studies with rats were designed to test the cumulative effects of repeated daily doses of ethanol. Male Sprague-Dawley rats were treated for 1, 2, 3, or 4 days either with ethanol orally in 4 doses of 1 g/kg each at 0, 1, 2, and 3 hours or with glucose orally in 4 isocaloric doses. Urine was collected at timed intervals up to 12 hours after each daily dose. The pattern of the increase in urinary folate levels was similar in all groups, whether treated for 1, 2, 3 or 4 days. These results suggest that repeated ethanol treatment can lead to a marked cumulative folate loss via increased urinary excretion and that increased urinary folate excretion may contribute to the development of folate deficiency in humans.

Influence of Mobiletten on the effect of alcohol drinking in man. First communication: Influence on the pharmacokinetics of ethanol.

The interaction of the drug Mobiletten with the pharmacokinetics of ethanol was studied in 15 probands. In these experiments, the maximal ethanol concentrations in blood were found to be significantly decreased and delayed. The ethanol elimination remained unchanged. The uptake of Mobiletten resulted in a remarkable decrease of the urine volume. The quantitative determination of the ethanol content in the expired air by alcotest technique was not significantly affected.