Clinical Interpretation of Urine Drug Tests: What Clinicians Need to Know About Urine Drug Screens.

Urine drug testing is frequently used in clinical, employment, educational, and legal settings and misinterpretation of test results can result in significant adverse consequences for the individual who is being tested. Advances in drug testing technology combined with a rise in the number of novel misused substances present challenges to clinicians to appropriately interpret urine drug test results. Authors searched PubMed and Google Scholar to identify published literature written in English between 1946 and 2016, using urine drug test, screen, false-positive, false-negative, abuse, and individual drugs of abuse as key words. Cited references were also used to identify the relevant literature. In this report, we review technical information related to detection methods of urine drug tests that are commonly used and provide an overview of false-positive/false-negative data for commonly misused substances in the following categories: cannabinoids, central nervous system (CNS) depressants, CNS stimulants, hallucinogens, designer drugs, and herbal drugs of abuse. We also present brief discussions of alcohol and tricyclic antidepressants as related to urine drug tests, for completeness. The goal of this review was to provide a useful tool for clinicians when interpreting urine drug test results and making appropriate clinical decisions on the basis of the information presented.

[Hysterectomy for benign pathology: Guidelines for clinical practice]. / Hystérectomie pour pathologie bénigne: recommandations pour la pratique clinique.

OBJECTIVE: The objective of the study was to provide guidelines for clinical practice from the French college of obstetrics and gynecology (CNGOF), based on the best evidence available, concerning hysterectomy for benign pathology. METHODS: Each recommendation for practice was allocated a grade which depends on the level of evidence (guidelines for clinical practice method). RESULTS: Hysterectomy should be performed by a high volume surgeon (>10 procedures of hysterectomy per year) (grade C). Rectal enema stimulant laxatives are not recommended prior to hysterectomy (grade C). It is recommended to carry out vaginal disinfection using povidone iodine solution prior to an hysterectomy (grade B). Antibioprophylaxis is recommended during a hysterectomy, regardless of the surgical route (grade B). The vaginal or the laparoscopic routes are recommended for hysterectomy for benign pathology (grade B), even if the uterus is large and/or the patient is obese (grade C). The choice between these two surgical approaches depends on others parameters, such as the surgeon's experience, the mode of anesthesia and organizational constraints (operative duration and medico economic factors). Hysterectomy by vaginal route is not contraindicated in nulliparous women (grade C) or in women with previous c-section (grade C). No specific technique to achieve hemostasis is recommended with a view to avoid urinary tract injuries (grade C). In the absence of ovarian pathology and personal or family history of breast/ovarian carcinoma, it is recommended to conserve ovaries in pre-menopausal women (grade B). Subtotal hysterectomy is not recommended in order to diminish the risk of per- or postoperative complications (grade B). CONCLUSION: The application of these recommendations should minimize risks associated with hysterectomy.

Chronic opioid therapy risk reduction initiative: impact on urine drug testing rates and results.

BACKGROUND: In response to epidemic levels of prescription opioid overdose, abuse, and diversion, routine urine drug tests (UDTs) are recommended for patients receiving chronic opioid therapy (COT) for chronic pain. However, UDT ordering for COT patients is inconsistent in primary care, and little is known about how to increase UDT ordering or the impact of increased testing on rates of aberrant results. OBJECTIVE: To compare rates and results of UDTs for COT patients before versus after implementation of an opioid risk reduction initiative in a large healthcare system. DESIGN: Pre-post observational study. PATIENTS: Group Health patients on COT October 2008-September 2009 (N = 4,821), October 2009-September 2010 (N = 5,081), and October 2010-September 2011 (N = 5,498). INTERVENTION: Multi-faceted opioid risk reduction initiative. MAIN MEASURES: Annual rates of UDTs and UDT results. KEY RESULTS: Half of COT patients received at least one UDT in the year after the initiative was implemented, compared to only 7 % 2 years prior. The adjusted odds of COT patients having at least one UDT in the first year of the opioid initiative were almost 16 times (adjusted OR = 15.79; 95 % CI: 13.96-17.87) those 2 years prior. The annual rate of UDT detection of marijuana and illicit drugs did not change (12.6 % after initiative implementation), and largely reflected marijuana use (detected in 11.1 % of all UDTs in the year after initiative implementation). In the year after initiative implementation, 10.7 % of UDTs were negative for opioids. CONCLUSIONS: The initiative appeared to dramatically increase urine drug testing of COT patients in the healthcare system without impacting rates of aberrant results. The large majority of aberrant results reflected marijuana use or absence of opioids in the urine. The utility of increased urine drug testing for COT patient safety and prevention of diversion remains uncertain.

Quantitative selenium speciation in human urine by using liquid chromatography-electrospray tandem mass spectrometry.

A liquid chromatography-electrospray-tandem mass spectrometry (ES-MS/MS) method was developed for the speciation analysis of four organic selenium species of relevance to human urinary metabolism, namely trimethylselenomium ion (TMSe(+)), selenomethionine (SeMet) and the two selenosugars, methyl 2-acetamido-2-deoxy-1-seleno-ß-D-galactos/-glucos-amine (SeGalNAc and SeGluNAc, respectively). Their chromatographic separation was achieved by using a cation exchange pre-column coupled in-series with a reversed-phase high-performance liquid chromatography column, along with an isocratic mobile phase. Online detection was performed using ES-MS/MS in selective reaction monitoring mode. SeGalNAc was detected as the major human urinary metabolite of selenium in the samples analysed, whereas TMSe(+) was detected in the urine of one volunteer before and after receiving a selenium supplement. SeMet was not detected as a urine excretory metabolite in this study. Spiking experiments performed with the urine samples revealed significant signal suppression caused by coeluting matrix constituents. To overcome such interferences, isotopically labelled (13)CD(3)(82)SeGalNAc was used as an internal standard, whereas in the absence of an isotopically labelled internal standard for TMSe(+), the standard addition method was applied. Quality control for the accurate quantitation of TMSe(+) and SeGalNAc was carried out by analysing spiked human urine samples with appropriate selenium standards over a concentration range of 10-50 µg Se L(-1). The method has achieved a limit of detection in the presence of urine matrix comparable to that of HPLC-inductively coupled plasma-mass spectrometry for the four selenium species: 1.0 µg Se L(-1) for TMSe(+), 5.6 µg Se L(-1) for SeMet, and 0.1 µg Se L(-1) for both SeGalNAc and SeGluNAc.

Association between 24 hour urinary α-tocopherol catabolite, 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (α-CEHC) and α-tocopherol intake in intervention and cross-sectional studies.

The objective is to determine the association between the 24 hour urinary α-tocopherol catabolite, 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (α-CEHC) and α-tocopherol intake in an intervention and a cross-sectional studies. In the 4-weeks intervention study, Japanese men (n = 10) consumed the test diet in week 1, and the test diet plus varying amounts of α-tocopherol in the three subsequent weeks: 21 µmol/d α-tocopherol in week 2, 63 µmol/d in week 3, and 125 µmol/d in week 4. A significant association between α-tocopherol intake and urinary α-CEHC was observed in this strictly controlled experiment (r = 0.99, p<0.001). In the cross-sectional study, all foods consumed over 4 consecutive days were recorded in 76 free-living young subjects (18-33 years). The association was weak, but a significant relationship was observed (r = 0.29, p<0.05) even in the cross-sectional study. In the cross-sectional study adults, mean estimated α-tocopherol intake calculated by urinary α-CEHC and the excretory ratio was 91% of their mean intake over the 4 days. The results show that urinary α-CEHC level reflected recent α-tocopherol intake in free-living young Japanese adults, and could be used as a measure of intake during the previous few days, both for group means and for individual rankings within a group.

Methods of assessment of magnesium status in humans: a systematic review.

To understand humans' requirements for magnesium and the effect of magnesium on health, it is important to identify sensitive and population-specific biomarkers of magnesium status. Thus, we assessed the effectiveness of different magnesium status biomarkers through a systematic review of published magnesium supplementation and depletion trials in healthy humans. The methods used in this study included a structured search on Ovid MEDLINE, EMBASE (Ovid) and Cochrane databases up to September 2008, followed by the use of formal inclusion/exclusion criteria, data extraction, validity assessment, and meta-analysis. A total of 20 potential biomarkers of magnesium status were assessed from 21 included publications. The majority of studies included were magnesium supplementation studies. Fewer magnesium depletion studies were identified. Available data analysis suggests that serum/plasma magnesium concentration, red blood cell (RBC) concentration and urinary magnesium excretion responded to dietary manipulation. For other biomarkers with available data, it was not possible to draw any conclusions about their usefulness as magnesium status biomarkers. The lack of data prevented detailed subgroup analysis. In conclusion, although limited data were available, serum/plasma magnesium concentration, RBC magnesium concentration and urinary magnesium excretion appear to be useful biomarkers of magnesium status in the general population. Further high-quality studies are needed to assess the effectiveness of existing and newly developed biomarkers, especially in populations that are vulnerable to magnesium deficiency.

Pediatric reference intervals for random urine calcium, phosphorus and total protein.

The aim of this study was to establish age appropriate reference intervals for calcium (Ca), phosphorus (P) and total protein (UTP) in random urine samples. All analytes were measured using the Roche MODULAR P analyzer and normalized to creatinine (Cr). Our study cohort consisted of 674 boys and 728 girls between 7 and 17 years old (y.o.), which allowed us to determine the central 95% reference intervals with 90% confidence intervals by non-parametric analysis partitioned by both gender and 2-year age intervals for each analyte [i.e. boys in age group 7-9 years (7-9 boys); girls in age group 7-9 years (7-9 girls), etc.]. Results for the upper limits of the central 95% reference interval were: for Ca/Cr, 0.27 (16,17 y.o.) to 0.46 mg/mg (7-9 y.o.) for the girls and 0.26 (16,17 y.o.) to 0.43 mg/mg (7-9 y.o.) for the boys; for P/Cr, 0.85 (16,17 y.o.) to 1.44 mg/mg (7-9 y.o.) for the girls and 0.87 (16,17 y.o.) to 1.68 mg/mg (7-9 y.o.) for the boys; for UTP/Cr, 0.30 (7-9 y.o.) to 0.34 mg/mg (10-12 y.o.) for the girls and 0.19 (16,17, y.o.) to 0.26 mg/mg (13-15 y.o.) for the boys. Upper reference limits decreased with increasing age, and age was a statistically significant variable for all analytes. Eight separate age- and gender-specific reference intervals are proposed per analyte.

Beating the system: a study of a creatinine assay and its efficacy in authenticating human urine specimens.

Creatinine concentration is commonly used to verify the authenticity of urine specimens submitted for illicit drug screening. This study evaluated creatinine screening of donor urine specimens as a tool for detecting substituted and/or tampered specimens. The study carried out creatinine assay of animal urine, fruit juices, and urine from creatine-supplemented subjects by a modified version of the Jaffe reaction. All specimens were analyzed for creatinine concentration in a chemistry-immuno analyzer. Results showed that urine specimens from common domestic pets, including cats, dogs, and horses, have creatinine values similar to normal human values. Most fruit juices tested contained no detectable creatinine, and the few that did showed poor "urine" chemical integrity. Creatine supplementation by donors was found not to provide an effective means of elevating creatinine concentration in urine when attempting to flush out water-soluble drugs in the body. Thus, the assay for creatinine proved useful for the detection of some but not all adulterated urine specimens.

Evaluation of the ARCHITECT urine NGAL assay: assay performance, specimen handling requirements and biological variability.

OBJECTIVES: NGAL (Neutrophil Gelatinase-Associated Lipocalin) has emerged as a new biomarker for the identification of acute kidney injury. Reliable clinical evaluations require a simple, robust test method for NGAL, and knowledge of specimen handling and specimen stability characteristics. We evaluated the performance of a new urine NGAL assay on the ARCHITECT analyzer. METHODS: Assay performance characteristics were evaluated using standard protocols. Urine specimen storage requirements were determined and biological variability was assessed in a self-declared apparently healthy population. RESULTS: Assay performance data showed good precision, sensitivity and lot-to-lot reproducibility. There was good short term 2-8 degrees C sample stability, however, long term storage samples must be kept at -70 degrees C or colder. The largest variance component in a biological variance study was within-day. CONCLUSIONS: The ARCHITECT NGAL assay proved to be a precise and reproducible assay for the determination of urine NGAL.

Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States.

BACKGROUND: Exposure to endocrine disruptors (EDs), including some phthalates, phytoestrogens and phenols can be quantified using biomarkers of exposure. However, reliability in the use of these biomarkers requires an understanding of the timeframe of exposure represented by one measurement. Data on the temporal variability of ED biomarkers are sparse, especially among children. OBJECTIVE: To evaluate intraindividual temporal variability in 19 individual urinary biomarkers (eight phthalate metabolites from six phthalate diesters, six phytoestrogens (two lignans and four isoflavones) and five phenols) among New York City children. METHODS: Healthy Hispanic and Black children (N=35; 6-10 years old) donated several urine samples over 6 months. To assess temporal variability we used three statistical methods: intraclass correlation coefficient (ICC), Spearman correlation coefficients (SCC) between concentrations measured at different timepoints, and surrogate category analysis to determine how well the tertile categories based on a single measurement represented a 6-month average concentration. RESULTS: Surrogate category analysis indicated that a single sample provides reliable ranking for all analytes; at least three of four surrogate samples predicted the 6-month mean concentration. Of the 19 analytes, the ICC was >0.2 for 18 analytes and >0.3 for 10 analytes. Correlations among sample concentrations throughout the 6-month period were observed for all analytes; 14 analyte concentrations were correlated at 16 weeks. CONCLUSIONS: The reasonable degree of temporal reliability and the wide range of concentrations of phthalate metabolites, phytoestrogens and phenols suggest that these biomarkers are appropriate for use in epidemiologic studies of environmental exposures in relation to health outcomes in children.

[The "incorrect" laboratory result. II: Common misinterpretations of laboratory results]. / Der "fehlerhafte" Laborbefund. Teil 2: Häufige Ursachen von Fehlinterpretationen labormedizinischer Befunde.

In the second part of our review the most frequent misinterpretations of laboratory results in the daily clinical practise are discussed. Special attention has been given to frequent misinterpretations in the analysis of electrolytes, enzymes and hormones in plasma/serum (pseudohyperkalemia, macroenzymes, macroprolactinemia). Misinterpretations of the testing of blood gases, serum glucose, lipid concentrations, and calcium are described in greater detail. In addition, potential errors in the urinanalysis and the importance of adequate sampling of blood specimens for coagulation testing are described. The hematological results can be misinterpreted in the presence of EDTA-induced pseudothrombocytenia and of irregular immunoglobulines. Immunological methods themselves can lead to misinterpretations of the laboratory result, e. g. caused by the high dose hook effect and interferences in the presence of rheumatoid factor or HAMA. Finally clinical relevant errors in the therapeutic drug monitoring are discussed which are associated with the limited specificity of the antibodies in the commonly used immunological tests.

PROCORAD's international intercomparisons highlight the evolution of techniques used to determine uranium in urine.

Inter-laboratory tests are a means of assessing the analytical coherence of medical laboratories. In radiotoxicology, this kind of exercise makes it possible to keep up with laboratory know-how and with the evolution and relative performances of analytical techniques. The intercomparison exercises organised by PROCORAD (Association for the Promotion of Quality Controls in Radiotoxicological Bioassays) provide an opportunity to compare and contrast radiochemistry and metrology for the in vitro analysis of urine and faeces. For uranium compounds, the development of new techniques such as inductively coupled plasma-mass spectrometry (ICP-MS), alpha spectrometry, and laser spectrofluorimetry makes it possible to compare the effectiveness of these protocols with respect to radiation protection monitoring, both in routine and special situations. Detection limits, flexibility, repeatability, reproducibility and isotopic quantification are the criteria considered in this study. The authors present the evolution of performances for the analysis of uranium in urine over the years. However, the goal of the laboratories taking part in these annual exercises is not only to check the accuracy of their results but also to have analytical discussions and the opportunity to exchange experiences that will enrich the group's general competence.

Analysis of over-the-counter dietary supplements.

OBJECTIVE: To determine if steroids containing over-the-counter (OTC) dietary supplements conform to the labeling requirements of the 1994 Dietary Supplement Health and Education Act (DSHEA). DESIGN: 12 brands of OTC supplements containing 8 different steroids were randomly selected for purchase in stores that cater to athletes. There are two androstenediones (4- and 5-androstene-3,17-dione), two androstenediols (4- and 5-androstene-3beta, 17beta-diol), and 4 more are 19-nor cogeners (19-nor-4- and 5-androstene-3,17-dione and 19-nor-4- and 5-androstene-3beta, 17beta-diol). MAIN OUTCOME MEASURES: 12 brands of OTC anabolic-androgenic supplements were analyzed by high-pressure liquid chromatography. RESULTS: We found that 11 of 12 brands tested did not meet the labeling requirements set out in the 1994 Dietary Supplement Health and Education Act. One brand contained 10 mg of testosterone, a controlled steroid, another contained 77% more than the label stated, and 11 of 12 contained less than the amount stated on the label. CONCLUSIONS: These mislabeling problems show that the labels of the dietary steroid supplements studied herein cannot be trusted for content and purity information. In addition, many sport organizations prohibit OTC steroids; thus, athletes who use them are at risk for positive urine test results. In this article we provide the details of the analyses, a summary of the steroids by name and structure, and information on the nature of the positive test results. Athletes and their physicians need this information because of the potential medical consequences and positive urine test results.

High incidence of significant urinary ascorbic acid concentrations in a west coast population--implications for routine urinalysis.

Examination of 4379 routine urinalysis specimens with dipsticks sensitive to ascorbic acid showed that 22.8% were positive specimens. The mean urinary vitamin C concentration in this population was 2120 mumol/L. There was a high rate of false-negative dipstick results for hemoglobin in patients with vitamin C in the urine. The highest false-negative rates were observed in urine samples containing less than 50 erythrocytes per high-power field. In further experiments when volunteers consumed supplemental oral USP vitamin C at doses of 100, 250, 500, and 1000 mg or vitamin C-containing fruit juices, even the lowest doses of oral vitamin C or juice resulted in sufficient urinary vitamin C to produce false-negative dipstick results in hemoglobin and glucose testing. To prevent potentially dangerous false-negative results, screening urinalysis protocols relying only on dipstick testing should include a check for urinary vitamin C or use a dipstick that is not subject to vitamin C interference.