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PubMed2005

Hui and Walter's latent-class reference-free approach may be more useful in assessing agreement than diagnostic performance.

BACKGROUND AND OBJECTIVE: Hui and Walter developed a latent class approach to assess the accuracy of a diagnostic procedure when no reference test is available. Our objective was to compare sensitivity and specificity estimates obtained with this reference-free approach and standard approaches, and to examine how and why they differed on a computerized tomography (CT) scan case study. STUDY DESIGN AND SETTING: We compared two sets of sensitivity and specificity estimates from four radiologists independently assessing tumoral and lymph node extension of 85 lung cancer patients with preoperative thoracic CT scan, those obtained relative to pathology findings from surgical specimens (reference set), and those derived from Hui and Walter's approach. RESULTS: The two sets of estimates significantly and markedly differed from each other. From simulations, we found that small-sample bias in Hui and Walter's estimates could be a major factor in explaining this difference. Furthermore, errors in pathology findings could account for part of this difference. Finally, our analyses revealed that the latent classes may differ intrinsically from the reference classes as defined from pathology findings and may have a different interpretation. CONCLUSION: Diagnostic parameters estimated with respect to latent classes may be more useful in providing a complete assessment of interobserver agreement than in assessing diagnostic performance.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Diagnostic performance of Triage for benzodiazepines: urine analysis of the dose of therapeutic cases.

We evaluated the diagnostic performance of Triage for benzodiazepines in 74 urine specimens from outpatients given therapeutic doses of benzodiazepines and compared the results of EMIT assays. Results obtained in all urine samples were confirmed using liquid chromatography-mass spectrometry (LC-MS). Overall agreement between results of Triage and EMIT assays was 73%. All of the Triage-positive samples were also positive by EMIT assays. Results of Triage and EMIT assays were different for 20 samples obtained from patients given thienodiazepines (etizolam, brotizolam, and clotiazepam) and nitrobenzodiazepines (nitrazepam, flunitrazepam, and clonazepam). LC-MS confirmed parent drugs in urine specimens, consistent with the prescriptions of drugs. The low agreement between Triage and EMIT results in this study might be due to low sensitivity of Triage for thienodiazepines. Thienodiazines are frequently prescribed benzodiazepines, and Triage panel is the most frequently used screening kit in Japan. It should be noted that negative results obtained by a Triage test might not mean the absence of thienodiazepines.

Benzodiazepines↗
PubMed1990

Comparative diagnostic performance of three radiological procedures for the detection of lumbar disk herniation.

Literature data on the diagnostic performance of phlebography, myelography, and CT scan applied to patients with suspected lumbar disk herniation (LDH) are analyzed to extract maximal information about their relative discriminatory power. Seventeen papers meeting the selection criteria contain 13 reports on myelography, 6 on phlebography, and 5 on CT. Sensitivity and specificity are considered simultaneously in logistic ROC space. The reports of each procedure are effectively summarized by a linear regression in logistic ROC space. Taking into account the individual confidence regions of sensitivity and specificity obtained from each report, the slope of the regression line is estimated by Generalized Least Squares (ML). This approach also allows to test the assumption of a common odds ratio (i.e., of a unit slope). The simply to determine common odds ratio as well as the perpendicular distance between the origin and the regression line (as a good approximation to the area under the ROC curve) are used as a measure for the discriminatory power of the procedures. For CT, homogeneity of sensitivity turns out to be much more likely than a common odds ratio. Based on the available, retrospective data, phlebography appears to have the highest performance in visualizing an LDH, followed by myelography and CT.

Humans↗
PubMed2005

Diagnostic Performance of Triagetrade mark for Benzodiazepines: Urine Analysis of the Dose of Therapeutic Cases.

We evaluated the diagnostic performance of Triage for benzodiazepines in 74 urine specimens from outpatients given therapeutic doses of benzodiazepines and compared the results of EMIT assays. Results obtained in all urine samples were confirmed using liquid chromatography-mass spectrometry (LC-MS). Overall agreement between results of Triage and EMIT assays was 73%. All of the Triage-positive samples were also positive by EMIT assays. Results of Triage and EMIT assays were different for 20 samples obtained from patients given thienodiazepines (etizolam, brotizolam, and clotiazepam) and nitrobenzodiazepines (nitrazepam, flunitrazepam, and clonazepam). LC-MS confirmed parent drugs in urine specimens, consistent with the prescriptions of drugs. The low agreement between Triage and EMIT results in this study might be due to low sensitivity of Triage for thienodiazepines. Thienodiazines are frequently prescribed benzodiazepines, and Triage panel is the most frequently used screening kit in Japan. It should be noted that negative results obtained by a Triage test might not mean the absence of thienodiazepines.

Journal Article↗
PubMed1995

Low-field versus high-field MR imaging of the knee: a comparison of signal behaviour and diagnostic performance.

A prospective study was undertaken to compare MR imaging of the knee obtained with low-field and high-field systems. In 10 subjects, MR imaging of the knee was performed on a 0.2 T permanent magnet and on a 1.5 T superconductive system. Similar spin echo (SE) and 3D-FISP (3D Fourier transform with steady state precession) acquisitions were obtained. Comparative image analysis was performed independently by four radiologists. Results show that the image quality and diagnostic performance delivered by state-of-the-art 0.2 T and 1.5 T systems is equivalent. Advantages of the 1.5 T system included: better signal-to-noise ratio, shorter scan times, better visualization of asymptomatic grade 1 meniscal degeneration on SE images. Advantages of 0.2 T images were: decreased chemical shift, susceptibility and flow artifacts, improved evaluation of subchondral bone on 3D-FISP images, slightly better patient tolerance. We conclude that, for MR imaging of the knee, a low-field system is a cost-effective alternative to more expensive superconducting units.

Adult↗
PubMed2006

MRI-guided biopsy of the prostate increases diagnostic performance in men with elevated or increasing PSA levels after previous negative TRUS biopsies.

OBJECTIVES: Repeatedly negative prostate biopsies in individuals with elevated prostate specific antigen (PSA) levels can be frustrating for both the patient and the urologist. This study was performed to investigate if magnetic resonance imaging (MRI)-guided transrectal biopsy increases diagnostic performance in individuals with elevated or increasing PSA levels after previous negative conventional transrectal ultrasound (TRUS)-guided biopsies. METHODS: 27 consecutive men with a PSA >4 ng/ml and/or suspicious finding on digital rectal examination, suspicious MRI findings, and at least one prior negative prostate biopsy were included. Median age was 66 years (mean, 64.5+/-6.8); median PSA was 10.2 ng/ml (mean, 11.3+/-5.5). MRI-guided biopsy was performed with a closed unit at 1.5 Tesla, an MRI-compatible biopsy device, a needle guide, and a titanium double-shoot biopsy gun. RESULTS: Median prostate volume was 37.4 cm3 (mean, 48.4+/-31.5); median volume of tumor suspicious areas on T2w MR images was 0.83 cm3 (mean, 0.99+/-0.78). The mean number of obtained cores per patient was 5.22+/-1.45 (median, 5; range, 2-8). Prostate cancer was detected in 55.5% (15 of 27) of the men. MRI-guided biopsy could be performed without complications in all cases. CONCLUSION: According to our knowledge, this is the largest cohort of consecutive men to be examined by MRI-guided transrectal biopsy of the prostate in this setting. The method is safe, can be useful to select suspicious areas in the prostate, and has the potential to improve cancer detection rate in men with previous negative TRUS-biopsies.

Biopsy↗
PubMed1988

Diagnostic performance of the hearing handicap inventory for the elderly (screening version) against differing definitions of hearing loss.

The diagnostic performance of the Hearing Handicap Inventory for the Elderly--Screening Version (HHIE-S) was evaluated against five definitions of hearing loss in 178 elderly subjects screened in primary care. Hearing loss was assessed by pure-tone audiometry. Using a score of greater than 8 as a cut point, the HHIE-S had sensitivities ranging from 53 to 72% and specificities ranging from 70 to 84% with the different definitions. The HHIE-S receiver-operating characteristics and likelihood ratios were similar regardless of hearing loss definition used. The HHIE-S is a valid, robust test for identifying hearing-impaired elderly, irrespective of the audiometric definition used to finally diagnose hearing difficulties.

Aged↗
PubMed2004

Measuring carotid stenosis on contrast-enhanced magnetic resonance angiography: diagnostic performance and reproducibility of 3 different methods.

BACKGROUND AND PURPOSE: The aim of this study was to compare diagnostic performance and reproducibility of 3 different methods of quantifying stenosis on contrast-enhanced magnetic resonance angiography (CEMRA), with intra-arterial digital subtraction angiography (DSA) as the reference standard. METHODS: 167 symptomatic patients scheduled for DSA, after screening Doppler ultrasound, were prospectively recruited to undergo CEMRA. Severity of stenosis was measured according to the North American Symptomatic Trial Collaborators (NASCET), European Carotid Surgery Trial (ECST), and the common carotid (CC) methods. Measurements for each method were made for 284 vessels (142 included patients) on both CEMRA and DSA in a blinded and randomized manner by 3 independent attending neuroradiologists. RESULTS: Significant differences in prevalence of severe stenosis were seen with the 3 methods on both DSA and CEMRA, with ECST yielding the least and NASCET the most cases of severe stenosis. Overall, all 3 methods performed similarly well in terms of intermodality correlation and agreement. No significant differences in interobserver agreement were found on either modality. With CEMRA, however, we found a significantly lower sensitivity for detection of severe stenosis with ECST (79.8%) compared with NASCET (93.0%), with DSA as reference standard. CONCLUSIONS: Uniformity of carotid stenosis measurement methods is desirable because patient management may otherwise differ substantially. All 3 methods are adequate for use with DSA. With CEMRA, however, this study supports use of the NASCET method because of improved sensitivity for detecting severe stenosis.

Adult↗
PubMed2004

Characterization of focal liver lesions with contrast-specific US modes and a sulfur hexafluoride-filled microbubble contrast agent: diagnostic performance and confidence.

PURPOSE: To assess whether characterization of solid focal liver lesions could be improved by using ultrasonographic (US) contrast-specific modes after sulfur hexafluoride-filled microbubble contrast agent injection, as compared with lesion characterization achieved with preliminary baseline US. MATERIALS AND METHODS: Four hundred fifty-two solid focal hepatic lesions that were considered indeterminate at baseline gray-scale and color Doppler US were examined after microbubble contrast agent injection performed by using low-acoustic-power contrast-specific modes during the arterial (10-40 seconds after injection), portal venous (50-90 seconds after injection), and late (100-300 seconds after injection) phases. Two readers independently and retrospectively reviewed baseline and contrast material-enhanced US scans and classified each depicted lesion as malignant or benign according to standard diagnostic criteria. Sensitivity, specificity, accuracy, and positive and negative predictive values and areas under the receiver operating characteristic curve (Az) were calculated by considering histologic analysis (317 patients) or contrast-enhanced helical computed tomography followed by serial US 3-6 months apart (135 patients) as the reference standards. RESULTS: Different contrast enhancement patterns were observed according to lesion characteristics. During the late phase, benign lesions were predominantly hyper- or isoechoic relative to the adjacent liver parenchyma, whereas malignant lesions were predominantly hypoechoic. Review of the contrast-enhanced US scans after baseline image review yielded significantly improved diagnostic performance (P <.05). Overall diagnostic accuracy was 49% before versus 85% after review of the contrast-enhanced scan for reader 1 and 51% before versus 88% after review of the contrast-enhanced scan for reader 2. Diagnostic confidence-that is, the Az-was 0.820 before versus 0.968 after review of the contrast-enhanced scan for reader 1 and 0.831 before versus 0.978 after review of the contrast-enhanced scan for reader 2. CONCLUSION: The use of contrast-specific modes with a sulfur hexafluoride contrast agent led to improved characterization of solid focal liver lesions.

Adenoma, Liver Cell↗
PubMed2006

Influence of disease severity and optic disc size on the diagnostic performance of imaging instruments in glaucoma.

PURPOSE: To evaluate the influence of disease severity and optic disc size on the diagnostic accuracy of three imaging technologies for structural assessment in glaucoma: confocal scanning laser ophthalmoscopy, scanning laser polarimetry, and optical coherence tomography. METHODS: One hundred five patients with glaucoma and 61 normal subjects were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS). All individuals underwent imaging with the GDx Variable Corneal and Lens Compensator (VCC; Carl Zeiss Meditec, Inc., Dublin, CA), the Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, GmbH, Dossenheim, Germany), and the Stratus OCT (Stratus OCT; Carl-Zeiss Meditec, Inc.) within a 6-month period. Severity of disease was based on the AGIS (Advanced Glaucoma Intervention Study) visual field score. To evaluate the influence of severity of glaucoma and optic disc size on the diagnostic accuracy of the imaging instruments, the sensitivities of the tests were fitted as a function of the AGIS score and disc area, by using logistic marginal regression models. RESULTS: The severity of visual field loss had a significant influence on the sensitivity of all imaging instruments. More severe disease was associated with increased sensitivity. This influence was similar among the three instruments. With regard to optic disc area, larger optic discs were associated with decreased sensitivity for the Stratus OCT parameter Average Thickness and the GDx VCC parameter Nerve Fiber Indicator, whereas small optic discs were associated with increased sensitivity. For the HRT II parameter Moorfields regression analysis classification, an inverse effect was observed. CONCLUSION: The diagnostic performances of the GDx VCC, HRT II, and Stratus OCT were significantly influenced by the severity of the disease and optic disc size. These covariates should be taken into account when comparing the performances of these tests for glaucoma diagnosis.

Aged↗
PubMed2003

High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis.

OBJECTIVE: We investigated the rheumatoid arthritis (RA) diagnostic performances of anti-cyclic citrullinated peptide antibody (anti-CCP) and antifilaggrin antibody (AFA) in comparison with RF and matrix metalloproteinase-3 (MMP-3). METHODS: We used a second generation enzyme-linked immunosorbent assay (ELISA) kit for the detection of anti-CCP. We constructed recombinant human filaggrin, which was citrullinated in vitro by human peptidylarginine deiminase, and subsequently used it as the coating antigen for AFA-ELISA. A total of 549 RA patients and 208 other rheumatic disease patients were included in the study. RESULTS: The specificities of anti-CCP (88.9%) and AFA (94.7%) were superior to those of RF (81.7%) and MMP-3 (49.5%). The sensitivity of anti-CCP (87.6%) was superior to all others. However, the sensitivity of AFA (68.7%) was inferior to those of RF (69.8%) and MMP-3 (75.7%). Furthermore, receiver operating characteristic curves of anti-CCP and AFA passed closer to the upper left corner than those of RF and MMP-3, and the areas under the curves (AUC) of AFA and anti-CCP were significantly larger. In addition, the AUC of anti-CCP was significantly larger than that of AFA. CONCLUSION: ELISA detection of antibodies to citrullinated antigens, especially a second generation anti-CCP, showed higher discriminative ability than other assays, including RF, and would be useful to aid the diagnosis of RA in clinical practice.

Adult↗
PubMed2004

Comparative diagnostic performance of two commercial rapid tests for malaria in a non-endemic area.

In the study reported here, the diagnostic performance of two new rapid tests for the diagnosis of malaria was evaluated in symptomatic patients in a non-endemic area. Of 557 consecutive patients, 109 (19.6%) had documented malaria. For the NOW ICT MALARIA P.f./P.v. (Binax, Portland, ME, USA) and OptiMAL IT (Diamed, Cressier, Switzerland) tests, respectively, sensitivity values were 96.3% and 79.8% (P-value, 0.0001), and specificity values were 98.8% and 98.4%. The NOW ICT test did not detect two of 80 Plasmodium falciparum infections, and it generated false-positive results for five patients. The OptiMAL IT test failed to detect ten of the P. falciparum infections, and it generated seven false-positive results. The results suggest that these rapid diagnostic tests for malaria may be useful, but they cannot replace microscopic examination of blood films.

Adolescent↗
PubMed2003

Diagnostic performance of intracardiac echogenic foci for Down syndrome: a meta-analysis.

OBJECTIVE: To synthesize the accumulated data on the diagnostic performance of intracardiac echogenic foci for Down syndrome, a meta-analysis was performed. DATA SOURCES: We conducted MEDLINE and EMBASE searches (1985 to August 2002) using the key words "intracardiac (echogenic) focus/foci," "golfballs," "trisomy 21," and "Down syndrome." Bibliographies of retrieved articles were also screened, and experts were contacted. Both single and multiple intracardiac echogenic foci qualified, regardless of cardiac location. Eligible studies included and described both chromosomally normal and abnormal fetuses; the fetal karyotype was unknown at the time of sonographic examination; and chromosomal status was confirmed by karyotype or postnatal clinical examination. TABULATION, INTEGRATION AND RESULTS: Sensitivity and specificity were recorded for intracardiac echogenic foci in a "combined" setting (regardless of the presence of other sonographic markers) and "isolated" setting (in the absence of other markers). Weighted estimates and summary receiver operating characteristic curves were calculated. Across 11 studies (51,831 pregnancies, 333 Down syndrome cases), random effects sensitivity and specificity were 26% (95% confidence interval 19, 34) and 95.8% (95% confidence interval 92.2, 97.8), respectively, with a positive likelihood ratio of 6.2 ("combined" setting, likelihood ratio 7.0; "isolated" setting, likelihood ratio 5.4). Summary receiver operating characteristic curves were also consistent with these values. With a 0.8% risk of amniocentesis-induced fetal loss, one fetus is lost per Down case detected when the background Down risk is 1:770. CONCLUSION: Intracardiac echogenic foci increase the risk of Down syndrome five- to seven-fold. This information should be considered in the decision making for amniocentesis in conjunction with the woman's background risk.

Down Syndrome↗
PubMed2006

Diagnostic performance of tests based on Trypanosoma cruzi excreted-secreted antigens in an endemic area for Chagas' disease in Bolivia.

The diagnostic performance of Trypanosoma cruzi excreted-secreted antigen (TESA)-based and conventional tests for Chagas' disease was evaluated in a field study with 742 sera from a population in an endemic area in the Department of Chuquisaca, Bolivia. Of the 742 samples, 329 (44.34 %) were positive in the TESA blot assay, which diagnosed 9 Trypanosoma cruzi-infected individuals missed by conventional serologic tests.

Adolescent↗
PubMed1999

Diagnostic performance of two antigen capture tests for the diagnosis of Plasmodium falciparum malaria in Zimbabwe.

OBJECTIVE: The objective was to compare the diagnostic performance of two antigen capture tests, ParaSight-F test and Immunochromatographic test (ICT), for the diagnosis of Plasmodium falciparum malaria. DESIGN: A comparative study. SETTING: Burma Valley, Mutare District, Manicaland in Zimbabwe. SUBJECTS: Patients attending the local clinic with clinical signs and symptoms associated with malaria infection. A blood film was collected from the patient and at the same time blood for the ParaSight-F test and the ICT was collected too. A total of 123 patients were diagnosed using the ICT test, the ParaSight-F test and microscopy which was used as a "gold" standard. MAIN OUTCOME MEASURES: True positives and negatives, false positives and negatives with reference to microscopy. RESULTS: The results indicate that ICT had a higher sensitivity (100%) than the ParaSight-F test (93.94%) but showing a lower specificity. The specificity for ICT (75%) is lower than the ParaSight-F test (81.2%) because of the presence of circulating P. falciparum histidine-rich protein-2 (PfHRP-2) in blood even after two weeks post treatment. Two slides that were negative for ParaSight-F tests showed positive on microscopy. However, 21 and 12 slides which were negative on microscopy, showed positive with ICT and ParaSight-F respectively. The fact that ICT detects very low quantities of PfHRP-2 puts it at a comparative advantage because it detects positives even at very low parasite rates. CONCLUSION: The availability of these two antigen capture tests, which are easy to perform, will reduce the number of severe cases by providing early diagnosis. The tests will also reduce the number of unnecessary treatments and irrational use of antimalarials.

Animals↗
PubMed1995

Measurement of the proportion of free to total prostate-specific antigen improves diagnostic performance of prostate-specific antigen in the diagnostic gray zone of total prostate-specific antigen.

OBJECTIVES: This study examined the clinical significance of non-complexed (free) prostate-specific antigen (PSA) in the differential diagnosis of prostate cancer with an emphasis on patients with total PSA values between 4.0 and 10.0 ng/mL (the diagnostic gray zone). METHODS: Serum samples were obtained from three specimen banks. Patient samples consisted of 55 untreated histologically confirmed primary cancer, 62 men with untreated benign prostatic disease histologically confirmed by 6 negative sextant biopsies, and 64 asymptomatic healthy male controls with normal digital rectal examinations and PSA values less than 4.0 ng/mL. All patients were between the ages of 50 and 75 years. Total PSA levels were determined using the PA immunoassay performed on the TOSOH AIA-1200 automated immunoassay instrument. Free PSA levels were determined using a monoclonal-polyclonal antibody sandwich radioimmunoassay. The proportion of free to total PSA was calculated by dividing the patient's free PSA value by the total PSA value. RESULTS: When all subjects were included, both total PSA and the proportion of free to total PSA significantly differentiated between patients with prostate cancer and patients with benign histologic conditions (P < 0.0001). However, in men with total PSA values between 4.0 and 10.0 ng/mL, the proportion of free to total PSA significantly differentiated between patients with benign and malignant histologic conditions (P = 0.0004), whereas the total PSA did not (P = 0.13). Among this subgroup of patients, the analysis of sensitivity and specificity showed that the proportion of free to total PSA had a clearly higher specificity compared with that of the total PSA at the same level of sensitivity. CONCLUSIONS: Measurement of the free PSA level in a patient's serum and calculation of the proportion of free to total PSA enhances the ability to distinguish benign histologic conditions from cancer while retaining high sensitivity for detecting cancer in men who present with total PSA levels between 4.0 and 10.0 ng/mL. A large-scale population-based study is currently in progress to confirm this preliminary finding.

Aged↗
PubMedDate not supplied

Diagnostic performance of the equine IgM capture ELISA for serodiagnosis of West Nile virus infection.

The objectives of these studies were to assess the diagnostic performance (sensitivity and specificity) of the IgM capture enzyme-linked immunosorbent assay (ELISA; MAC) for diagnosis of West Nile (WN) virus in horses and to examine the performance of this test by using different criteria for seropositivity. A total of 36 horses classified as WN virus infected (group 1) and 383 horses from 4 subpopulations of hoses classified as noninfected (groups 2, 3, 4, and 5) were used in the study. The sensitivity (proportion of infected horses that tested positive for WN virus IgM antibodies) and specificity (proportion of noninfected horses that tested negative) were calculated at different cutoff points by using receiver operating curve (ROC) analysis. Using a selected cutoff point = 2.0, the sensitivity and specificity of the MAC were 91.7 and 99.2%, respectively. The area under the ROC curve = 0.95 (95% confidence interval [CI], 0.89 to 1.0), suggesting that the MAC is a useful tool for diagnosis of recent WN virus exposure in horses. In fulfillment of the 2nd objective, 2 other indices were developed and these indices approached 1.0 for the AUC with smaller 95% CIs. These indices were then used to test 602 additional diagnostic samples submitted from suspect horses between 2002 and 2004. Using the standard cutoff, 194 (32%) of the horses were interpreted as positive. Utilizing newly predicted cutoff criteria from each index, additional horses were identified as positive. In conclusion, the MAC as used for identification of WN virus-diseased horses undergoing recent exposure performs reliably at the standard cutoff for seropositivity. A negative test might not completely rule out WN virus disease, but horses that test negative were most likely not exposed to WNV. Performance of the test can be further improved by investigation of other indexes of seropositivity.

Animals↗
PubMedDate not supplied

Diagnostic performance of the EMIT-tox benzodiazepine immunoassay, FPIA serum benzodiazepine immunoassay, and radioreceptor assay in suspected acute poisoning.

We evaluated the diagnostic performance of the EMIT-tox serum benzodiazepine assay adapted to a Hitachi 717 analyzer (EMIT), the Abbott ADx serum benzodiazepine fluorescence polarization immunoassay (FPIA), and a radioreceptor assay (RRA) in 113 patients with suspected acute poisoning. The reference method was high-performance liquid chromatography with ultraviolet detection after solid-phase extraction. For the discrimination between negative and positive samples, the areas under the receiver-operating characteristic (ROC) curves were 0.976, 0.991, and 0.991 for EMIT (cutoff, 50-ng/mL diazepam), FPIA (cutoff, 12-ng/mL nordiazepam), and RRA (cutoff, 50-ng/mL diazepam), respectively. For the discrimination between non-toxic and toxic concentrations, the areas under the ROC curves were 0.896, 0.893, and 0.933, respectively. EMIT (with the cutoff lowered to 50 ng/mL), FPIA, and RRA can be reliably used to screen for the presence of benzodiazepines in serum, but in many cases they cannot discriminate between toxic and nontoxic concentrations.

Anti-Anxiety Agents↗