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Background: Recent evidences suggest that gallbladder drainage is the treatment of choice in elderly or high-risk surgical patients with acute cholecystitis (AC). Despite better outcomes compared to other approaches, endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is burdened by high mortality. The aim of the study was to evaluate predictive factors for mortality in high-risk surgical patients who underwent EUS-GBD for AC. Methods: A retrospective analysis of a prospectively maintained database was performed. Electrocautery-enhanced lumen-apposing metal stents were used; all recorded variables were evaluated as potential predictive factors for mortality. Results: Thirty-four patients underwent EUS for suspected AC and 25 (44% male, age 78) were finally included. Technical, clinical success rate and adverse events rate were 92%, 88%, and 16%, respectively. 30-day and 1-year mortality were 12% and 32%. On univariate analysis, age-adjusted Charlson Comorbidity Index (CCI) (OR 20.8[4–68.2]), acute kidney injury (AKI) (OR 21.4[2.6–52.1]) and clinical success (OR 8.9[1.2–11.6]) were related to 30-day mortality. On multivariate analysis, CCI and AKI were independently related to long-term mortality. Kaplan–Meier curves showed an increased long-term mortality in patients with CCI > 6 (hazard ratio 7.6[1.7–34.6]) and AKI (hazard ratio 11.3[1.4–91.5]). Conclusions: Severe comorbidities and AKI were independent predictive factors confirming of long-term mortality after EUS-GBD. Outcomes of EUS-GBD appear more influenced by patients’ conditions rather than by procedure success.

ABSTRACTIntroduction: The pathogenesis of Inflammatory bowel diseases (IBD) is multifactorial, with interactions between genetic and environmental factors. Despite the existence of genetic factors being largely demonstrated by epidemiological data and several genetic studies, only a few findings have been useful in term of disease prediction, disease progression and targeting therapy.Areas covered: This review summarizes the results of genome-wide association studies in Crohn’s disease, the role of epigenetics and the recent discovery by genetic studies of new pathogenetic pathways. Furthermore, it focuses on the importance of applying genetic data to clinical practice, and more specifically how to better target therapy and predict potential drug-related toxicity.Expert opinion: Some genetic markers identified in Crohn`s disease have allowed investigators to hypothesize about, and in some cases, prove the usefulness of new specific therapeutic agents. However, the heterogeneity and complexity of this disease has so far limited the daily clinical use of genetic information. Finally, the study of the implications of genetics on therapy, either to predict efficacy or avoid toxicity, is considered still to be in its infancy.

Despite the remarkable improvements achieved in the management of metastatic melanoma, there are still unmet clinical needs. A considerable fraction of patients do not respond to immune and/or targeted therapies due to primary and acquired resistance, report high-grade immune-related adverse events and lack alternative treatment options. To design effective combination therapies, we set up a functional ex vivopreclinical assay based on a drop-out genetic screen in metastatic melanoma patient-derived xenografts (PDXs). We showed that this approach can be used to isolate actionable vulnerabilities predictive of drug efficacy. In particular, we highlighted that the dual targeting of Aurora kinase A and MEK employing the combination of alisertib and trametinib (AT) is highly effective in a cohort of metastatic melanoma PDXs both ex vivoand in vivo. In particular, AT combination outperformed the standard-of-care therapy in both BRAF-mutant PDXs and in targeted therapy resistant models. Furthermore, AT treatment modulates several critical cancer pathways, including an early metabolic reprogramming which leads to the transcriptional upregulation of the fatty acid oxidation (FAO) pathway. This acquired trait unveiled an additional point of intervention for pharmacological targeting, and indeed the triple combination of AT with FAO inhibitor etomoxir proved to be further beneficial inducing tumor regression and remarkably prolonging mice overall survival.

We investigate the electronic and magnetic properties of TbPc2single ion magnets adsorbed on a graphene/Ni(111) substrate, by density functional theory (DFT), ab initiocomplete active space self-consistent field calculations, and X-ray magnetic circular dichroism (XMCD) experiments. Despite the presence of the graphene decoupling layer, a sizable antiferromagnetic coupling between Tb and Ni is observed in the XMCD experiments. The molecule–surface interaction is rationalized by the DFT analysis and is found to follow a relay-like communication pathway, where the radical spin on the organic Pc ligands mediates the interaction between Tb ion and Ni substrate spins. A model Hamiltonian which explicitly takes into account the presence of the spin radical is then developed, and the different magnetic interactions at play are assessed by first-principle calculations and by comparing the calculated magnetization curves with XMCD data. The relay-like mechanism is at the heart of the process through which the spin information contained in the Tb ion is sensed and exploited in carbon-based molecular spintronics devices.

Deubiquitinating enzymes are key regulators of the ubiquitin-proteasome system and cell cycle, and their dysfunction leads to tumorigenesis. Our in vivodrop-out screens in patient-derived xenograft models identify USP7 as a regulator of melanoma. We show that USP7 downregulation induces cellular senescence, arresting melanoma growth in vivoand proliferation in vitroin BRAF- and NRAS-mutant melanoma. We provide a comprehensive understanding of targets and networks affected by USP7 depletion by performing a global transcriptomic and proteomics analysis. We show that RRM2 is a USP7 target and is regulated by USP7 during S phase of the cell cycle. Ectopic expression of RRM2 in USP7-depleted cells rescues the senescent phenotype. Pharmacological inhibition of USP7 by P5091 phenocopies the shUSP7-induced senescent phenotype. We show that the bifunctional histone deacetylase (HDAC)/LSD1 inhibitor domatinostat has an additive antitumor effect, eliminating P5091-induced senescent cells, paving the way to a therapeutic combination for individuals with melanoma.

BACKGROUND Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in seizures, hemorrhage, recurrent headaches, and focal neurologic deficits. These CCMs can occur as sporadic or autosomal dominant conditions, although with incomplete penetrance and variable clinical expression. Three CCM loci have been identified, on chromosomes 7q21-22 (CCM1; Online Mendelian Inheritance in Man [OMIM] 116860), 7p13-15 (CCM2; OMIM 603284), and 3q25.2-27 (CCM3; OMIM 603285), and 3 genes have been cloned, KRIT1 on CCM1, MGC4607 on CCM2, and PDCD10 on CCM3. Mutations in KRIT1 account for more than 40% of CCMs. OBJECTIVE To describe the results of a comprehensive evaluation of 5 Italian families affected with CCM. DESIGN Clinical, magnetic resonance imaging, and KRIT1 gene analysis. SETTING University academic teaching hospitals. PATIENTS Fifteen patients with CCM diagnosed according to defined criteria and 45 at-risk, symptom-free relatives. RESULTS Three novel and 2 described mutations were found in KRIT1. The families included 33 KRIT1 mutation carriers, 57.6% of whom had no symptoms. Magnetic resonance imaging revealed CCM lesions in 82.3% of symptom-free mutation carriers. CONCLUSIONS The data confirm both incomplete clinical and neuroimaging penetrance in families with the KRIT1 mutation. This consideration is important in genetic counseling. Moreover, the data emphasize both the importance of magnetic resonance imaging in the diagnosis of CCM and the potential for DNA-based diagnosis to identify subjects at risk.Arch Neurol. 2007;64:843-848 --

Intraoperative [111In]-pentetreotide scintigraphy with a hand-held gamma detector probe has recently been proposed to increase the intraoperative detection rate of small neuroendocrine tumors and their metastases. We report a case of a 28-yr-old woman with ectopic Cushing’s syndrome due to an ACTH-secreting bronchial carcinoid, in whom the use of radioguided surgery improved disease management. At presentation, radiolabeled pentetreotide scintigraphy was the only procedure able to detect the ectopic source of ACTH. After radiologic confirmation, the patient underwent removal of a bronchial carcinoid, with disease persistence. After surgery, pentetreotide scintigraphy showed pathologic uptake in the mediastinum not previously detected at surgery and only subsequently confirmed by radiologic studies. Despite a second thoracic exploration, hormonal, scintigraphic, and radiological evidence of residual disease persisted. Radioguided surgery was then performed using a hand-held gamma probe 48 h after iv administration of a tracer dose of radiolabeled [111In-DTPA-D-Phe1]-pentetreotide, which permitted detection and removal of multiple residual mediastinal lymph node metastases. Clinical and radiologic cure, with no evidence of tracer uptake at pentetreotide scintigraphy, was subsequently observed. The use of an intraoperative gamma counter appears a promising procedure in the management of metastatic ACTH-secreting bronchial carcinoids.

More than 30 genetic variants of serum cholinesterase butyrylcholinesterase, BChE have been described. Some of them the atypical and the fluorideresistant variants are well known because carriers are prone to develop prolonged apnea following the administration of the muscle relaxant succinylcholine. Genotype characterization is therefore important in order to prevent such episodes. Genetic studies have so far focused on selected individuals or families rather than on the random population.

This paper is about the automation of the pre-analytical phase in a biochemical laboratory, which performs more than 3.7 million tests per year. The paper presents how an investment in the laboratory can be evaluated considering both economic criteria, future performance and service quality. The study comprises a workflow analysis of biological materials and information, the corresponding data collection and the use of simulation for performance evaluation. Alternative scenarios have been considered in terms of personnel, pre-analytical devices and management policies. The final scenario has been chosen according to economic criteria among a set of feasible scenarios, able to satisfy constraints.

AbstractFollowing up previous experience with External Quality Assessment (EQA) and Proficiency Testing Programs (PTP) on drugs of abuse (DoA) testing in Italy and in other European countries, the government of the Lombardy Region, first among Italian regions, established in 1995 a compulsory EQA scheme for laboratories authorized to perform these tests. The purpose of the present work is the description of the program and the overall evaluation of the results obtained in the first three annual cycles (1995–1998).During each annual cycle laboratories received 22 urine samples; some samples were collected from patients (“real samples”) and some were “spiked” urine samples. Both types of samples could contain the following substances/classes of substances: opiates, cocaine, cannabinoids, methadone, buprenorphine, benzodiazepines, barbiturates. Type A laboratories used an immunological screening method; they expressed the results as concentrations. Type B laboratories, authorized to perform screening methods followed by confirmatory techniques, searched for and identified single substances and provided an interpretation on possibly taken drugs.During the study period the laboratories produced about 21 000 analytical results. Among them, falsenegative results were 0.9% of true positives, and falsepositive results were 0.7% of true negatives. Performance using the spiked samples was better than using real samples, and performance of type B laboratories better than that of type A.The results obtained during the program are consistent with those of other quality control programs. This program, in addition, has provided information on the status of DoA testing in the Lombardy region's laboratories, in particular on their analytical performance, on the quality of interpretation of results and on a degree of improvement achieved during the program.

AbstractThe Immediate Response Mobile Analyzer (IRMA) is a selective and portable point-of-care testing (POCT) blood gas, electrolyte and hematocrit (Hct) analyzer. The overall analytical performance was evaluated in a two-center study involving two Italian hospital laboratories, following the guidelines suggested by the manufacturer (based on the NCCLS protocol), after a preliminary evaluation of their formal validity. The IRMA was compared to the analyzers used in the routine laboratory as reference. The considered parameters were pH, pO2, pCO2, Na+, K+, ionized calcium and Hct. When using the aqueous quality control material provided by the manufacturer most of the parameters showed good precision, with the exception of pCO2and pO2that showed high CVs on two of the three levels of the aqueous control. We could demonstrate that this imprecision was material-related and was reduced when using a different material (blood equilibrated by tonometry). With tonometred blood for pO2and pCO2and the aqueous material for the remaining parameters the CVs were all below 5%, ranging from 0.08% to 2.8%. The IRMA results correlated adequately with the comparison instruments, with the exception of sodium and ionized calcium where contradictory results were obtained in the two centers.

We report near-field photocurrent (PC) measurements performed on boron-implanted silicon and acquired at λ = 633, 1330, 1550 nm corresponding to photon energies of 1.96, 0.93, and 0.80 eV, respectively. The second and the third energies are below the silicon energy gap (Egap = 1.12 eV), representing incident radiation to which Si is virtually transparent. The PC images acquired at λ = 1330 and 1550 nm reveal the presence of boron clusters which are a consequence of B-implantation and rapid thermal annealing at 1100 °C. Boron clusters behave as metal clusters embedded into the silicon matrix and introduce gap states which give rise to the observed photocurrent. At energies larger than the Si energy gap the near-field PC images give information about subsurface defects not related to boron and with no correspondence in the surface topography.

Following a major environmental accident near Seveso, Italy, on July 10, 1976, we attempted to determine if the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) released into the atmosphere had any effect on the liver function and lipid metabolism of exposed children. From July 1976 to June 1982, we analyzed the results of more than 4500 laboratory tests (alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, alkaline phosphatase, cholesterol, and triglycerides in plasma and δ-aminolevulinic acid in urine) in a population of about 1500 children aged 6 to 10 years at the moment of the accident. The children exposed to the highest concentration of TCDD showed alterations in serum γ-glutamyltransferase and alanine aminotransferase activity compared with the control group. These differences were restricted to values inside limits set from the lower end of the normal range to slightly above it. The observed abnormalities were slight and disappeared with time.(JAMA 1986;256:2687-2695)

Sunspot data from the Catania Astrophysical Observatory, covering cycles 18, 19, and 20 (1943–1977) have been analyzed, taking into account, besides the usual parameters, the number n of zones, namely latitude belts 5° wide, showing sunspot activity and the area covered by spots for each of these zones. A comparison between our conclusions and those drawn from other authors on the same subject is made.

Screening recommendations for colorectal cancer include sigmoidoscopy in asymptomatic, average risk persons aged 50 and over and colonoscopy every three to five years in high risk groups. Little is known about the eligible population's compliance with endoscopic screening. This is the first Italian report of an endoscopic screening programme for colorectal cancer patients' relatives.

We investigate the possibility of observing the effects of magnetic reconnection inside a current sheet forming in a coronal streamer in the extended corona. In particular we study the possibility to observe with the UVCS of SOHO the excitation of the tearing instability in the current sheet.

The importance of evaluating receptors for estrogen and progestin in human breast cancer has been pointed out by many authors. In the absence of a reference standard, receptor assays must be controlled by intra and interlaboratory quality control programs. Much interlaboratory variability exists due to non-uniform analytical protocols, non-uniform ligands, intrinsic errors and also errors in computation methods. The goals of our Italian Qualtiy Control Program on Multicenter Trials are to standardize the anaytical procedures and computation methods. Twenty Italian laboratories participated in the Quality Control Program. Each specimen was assayed for steroid receptor content according to the standardized dextran-coated-charcoal method. Data were subjected to computerized analyses by 5 different methods of calculation (Scatchard plot, direct plot, Lineweaver-Burk method, Brunauer-Emmet-Teller analysis, single-point approach). The results were than evaluated to identify intra- and inter-assay variation coefficients and to define other statistical parameters. The authors suggest different calculation methods depending on the specific experimental and/or physiopathological conditions.

Since 1979 the quality control design proposed by the Italian ad hoc Committee has evaluated several lyophilized preparations with scalar receptor content; this permits the identification by linear regression analysis of systematic and non systematic errors. At present 41 laboratories from most of the national regions have joined the Italian Committee. The overall results of five years application of quality assurance in Italy show that there was a different pattern of imprecision with satisfactory indexes for intralaboratory performances but major variations in interlaboratory controls. There was also a remarkable difference of variability indices between the so-called « expert » and « new » laboratories; this problem can be reduced with practical seminars for new centers. On the basis of the results and experience achieved the Committee is starting another program of quality assurance for different new methodologies to provide guidelines for international working reference standards.

This article presents results of the first Italian quality control program for determining the estradiol receptor on lypophilized guinea pig and calf uteri. Despite considerable variability in quantitative terms, the results concur in ability to define samples as positive or negative for receptor content. One of the parameters that most strongly influences accuracy of determination of receptor concentration is protein assay. The evaluation of several lyophilized preparations at scalar concentrations permitted identification, by linear regression, for each laboratory of the systematic and non-systematic variables. More comparable results will be forthcoming when a standardized methodology program has been fully adopted.

Only free magnesium has biological activity: technology for measuring the ionized fraction of magnesium is now available via ion-selective electrodes. We have evaluated an instrument (AVL 988/4) which determines ionized magnesium (cMg2+) with an ion-selective electrode based on the ionophore ETH 7025. The selectivity of the electrode is adequate for the ions normally present in plasma, except for calcium: the interference is automatically corrected by simultaneous measurements of calcium with compensation for the calcium interference to the magnesium signal. We have first verified possible interferences caused by sampling procedures: known silicon interference has been avoided by use of glass tubes (BD Vacutainer with no additive, code 7626); heparin interference has been measured and found significant above 20 UI. mL-1 of plasma. Instrument evaluation according to NCCLS protocol gives the following imprecision results on 20 replicated analyses: cMg2+ (mmol. L-1) 1.29, 0.76, 0.23, CVs% (within-run) 0.67, 0.67, 3.00 and CVs% (between-run) 4.06, 3.91, 5.89 respectively. Linearity (in the range 0.23-1.60 mmol. L-1) was: measured cMg2+ = 0.981. (calculated cMg2+) + 0.009 mmol/L; r = 0.999. In healthy adults (n = 103) cMg2+ was in the range 0.46-0.74 mmol- L-1 (with a mean of 0.60 mmol/L and normal distribution). These values represent 57% to 84% of serum total magnesium concentration (TMg) (mean 71%). pH dependence of cMg2+ is present, usually to a lower extent with respect to cCa2+, but it seems different in patients with real or in vitro provoked acidosis and in hemodialyzed patients. Citrate interference on ionized magnesium measurements was found both in vitro and in vivo, whilst that due to lactate was demonstrated only in vitro. On a wide range of cMg2+ (n=100), a good correlation is obtained both with TMg and ultrafiltrable Mg (UFMg): cMg2+ = 0.723.TMg + 0.008 mmol. L-1, r = 0.978; cMg2+ = 0.912-UFMg + 0.10 mmol- L-1, r= 0.968, respectively. The ionized magnesium in ultrafiltrate was found 25% lower than that in serum. The lifespan of the electrode, evaluated on the basis of both time fiom installation and on number of measured samples, was estimated longer than 4 months and able to analyze more than 1500 samples, whichever comes first. The four electrodes we used during 18 months behaved all the same way. The correlation between measurements performed in whole blood (WB-cMg2+) and in the corresponding serum (S-cMg2+) was excellent: WB-cMg2+ = 0.954. S-cMg2+ +0.02 mmol- L-1; r = 0.998; n = 60.

We investigated the presence of colony-stimulating factor (CSF) in supernatants obtained from TS/A, a new metastatic murine cell line, and from its high-and low-metastatic clonal derivatives (E and F clones, respectively). TS/A cells produced a CSF in vitro that induced proliferation and differentiation of murine monocytic and granulocytic progenitors in agar cultures. In TS/A-bearing mice remarkable splenomegaly, blood granulocytosis and thymus depletion were observed along with a stimulatory activity in serum and a strong proliferative activity both in spleen and in bone marrow populations. Conditioned media from E clones showed an in vitro colony-stimulating activity greater than those of F clones. Mice injected subcutaneously with cells of all clones studied showed granulocytosis, splenomegaly and thymus depletion, although to varying degrees. However, no direct correlation between granulocytosis-splenomegaly and the number of spontaneous lung metastases was observed.

Some tumors are known to produce colony-stimulating factors (CSF). In mice bearing s.c. Ehrlich tumor (ET) we observed that tumor growth is responsible for hemopoietic perturbations in which the increase of granulocytic-macrophagic precursors (CFU-C) in bone marrow and in the spleen represents a remarkable aspect. CFU-C in bone marrow from ET-bearing mice are more sensitive than CFU-C from normal mice to CSF from L-cells (LC-CM), mouse embryo fibroblasts (MEF-CM) and from the same tumor (ET-CM). Macrophages from normal and from ET-bearing mice exert the same effect on the proliferation of normal bone marrow CFU-C.

2,3,7,8-Tetrachlorodibenzo-p-dioxin levels (TCDD) were measured in serum specimens from Seveso, Italy, residents, who were potentially highly exposed to the 1976 explosion, and in controls. The residents were chosen so as to represent those who did and did not develop chloracne. Levels of TCDD as high as 56,000 parts per trillion (ppt) were found in these serum specimens that were collected in 1976. These TCDD levels are the highest ever reported, and yet almost all clinical laboratory tests on these individuals were normal; any abnormal test result was only transitory in nature. These findings are unique in linking clinical histories to TCDD levels following an acute exposure.

a and ß-tryptase genes cluster on the short arm of human chromosome 16 and encode lineage-associated serine proteases that are abundantly expressed in mast-cells and, in trace amounts, in basophils. Under physiologic conditions no other myeloid cells express tryptases. However, in several myeloid leukemia cell lines and in AML blasts, the level of tryptase is elevated. In an attempt at correlating the levels of tryptase with cytogenetic features and the KIT and FLT3 mutational status, we analyzed serum samples collected at diagnosis from 150 AML and 57 ALL adult patients. The total serum concentration was determined by UniCAP 100 and UniCAP Tryptase Fluorenzyme Immunoassay Kit (Pharmacia-Upjohn, Uppsala, Sweden). The median value of tryptase level in the control group (50 healthy people; mean age 35 y, range 20–50; M/F= 26/24) amounted to less than 5 ng/ml, ranging from 1 to 15 ng/ml. We detected elevated tryptase levels (more than 15 ng/ml) in 66 out of 150 AML-patients (44%) and in 1 out of 57 ALL-patients (1.75%; median value 1.2 ng/ml) (p = < 0.0005, Fisher’s exact test ). In AMLs data showed that elevated tryptase values are significantly bound to patients with t(8;21) (n = 26, p = <0.0001) and inv(16) (n = 17, p = 0.035). Furthermore, we found a strong correlation between tryptase < 15 ng/ml and normal karyotype (n = 58 ; p = <0.0001). By contrast, we didn’t find any correlation between the levels of tryptase and t(15;17) (n = 12, p = 0.227), abnormal chr 5 or 7 (n = 9, p = 0.507), +8 (n = 6, p = 0.229), complex karyotype (n = 9, p = 1.000) or other abnormalities (n = 14, p = 0.778). A mutational screening for KIT (exon 2,8,10,11,and 17) and FLT3 (exon 14,15 and 20) was performed on 67/150 (45%) and 82/150 (55%) patients with AML, respectively. We recorded a significant association between high tryptase levels and the presence of KIT mutation (Fisher’s exact test: p = 0.012). No correlation was found between levels of tryptase and FLT3 mutational status (Fisher’s exact test: p = 0.803).In conclusion, data suggest that elevated serum tryptase levels at diagnosis are frequently associated with Core Binding Factor and with KIT mutated AML’s.

MODULAR ANALYTICS (Roche Diagnostics) (MODULAR ANALYTICS, Elecsys and Cobas Integra are trademarks of a member of the Roche Group) represents a new approach to automation for the clinical chemistry laboratory. It consists of a control unit, a core unit with a bidirectional multitrack rack transportation system, and three distinct kinds of analytical modules: an ISE module, a P800 module (44 photometric tests, throughput of up to 800 tests/h), and a D2400 module (16 photometric tests, throughput up to 2400 tests/h). MODULAR ANALYTICS allows customised configurations for various laboratory workloads. The performance and practicability of MODULAR ANALYTICS were evaluated in an international multicentre study at 16 sites. Studies included precision, accuracy, analytical range, carry-over, and workflow assessment. More than 700 000 results were obtained during the course of the study. Median between-day CVs were typically less than 3% for clinical chemistries and less than 6% for homogeneous immunoassays. Median recoveries for nearly all standardised reference materials were within 5% of assigned values. Method comparisons versus current existing routine instrumentation were clinically acceptable in all cases. During the workflow studies, the work from three to four single workstations was transferred to MODULAR ANALYTICS, which offered over 100 possible methods, with reduction in sample splitting, handling errors, and turnaround time. Typical sample processing time on MODULAR ANALYTICS was less than 30 minutes, an improvement from the current laboratory systems. By combining multiple analytic units in flexible ways, MODULAR ANALYTICS met diverse laboratory needs and offered improvement in workflow over current laboratory situations. It increased overall efficiency while maintaining (or improving) quality.

Focuses on the decision of Australian professional lacrosse player Peter Inge to play in the U.S. Interest of Inge in the game; Efforts of Inge to be admitted in Boston Cannons team in the country; Records of Inge while playing in the team; Opportunity for other Australian lacrosse players to play in the U.S.

The test principle and the optimization of the reactive ingredients are described for the one-step dip-and-read immunochromatographic FRONTLINE® rapid tests for drugs-of-abuse testing in urine samples. In a multicenter evaluation the rapid tests were compared with FPIA and EMIT immunoassays. Discrepant results were further analyzed by gas chromatography-mass spectrometry methods. In the comparison of the cannabinoids rapid tests versus both immunoassays using clinical and forensic urine samples (399 versus FPIA and 755 versus EMIT), sensitivities and specificities were 97% or better for both comparisons. For cocaine, a sensitivity of 100% versus both routine technologies was obtained, whereas the specificity was reduced somewhat to 91% because of some cross-reactivity with metabolites of methadone and of clozapine. Specificity was very high for the cocaine rapid tests (98–100%) when applied to urine samples of persons not in a methadone maintenance program. Sensitivities and specificities for the opiates rapid tests were 99% or better at all sites when compared with the routine methods. In the screening of about 1200 clinical urine samples for cannabinoids, cocaine or opiates misuse only six samples would have stayed undetected by rapid test analyzes. These results show the FRONTLINE assays allow a reliable and immediate screening for drugs of abuse.