Clinical Performance Characteristics Research Articles

1209 PERSONALIZED PSA TESTING USING GENETIC VARIANTS CAN POSSIBLY DECREASE THE NUMBER OF PROSTATE BIOPSIES

You have accessJournal of UrologyProstate Cancer: Detection and Screening I1 Apr 20121209 PERSONALIZED PSA TESTING USING GENETIC VARIANTS CAN POSSIBLY DECREASE THE NUMBER OF PROSTATE BIOPSIES Brian T. Helfand, Stacy Loeb, Matthias D. Hofer, Dae Y. Kim, Qiaoyan Hu, Phillip R. Cooper, Barry B. McGuire, and William J. Catalona Brian T. HelfandBrian T. Helfand Chicago, IL More articles by this author , Stacy LoebStacy Loeb New York, NY More articles by this author , Matthias D. HoferMatthias D. Hofer Chicago, IL More articles by this author , Dae Y. KimDae Y. Kim Chicago, IL More articles by this author , Qiaoyan HuQiaoyan Hu Chicago, IL More articles by this author , Phillip R. CooperPhillip R. Cooper Chicago, IL More articles by this author , Barry B. McGuireBarry B. McGuire Chicago, IL More articles by this author , and William J. CatalonaWilliam J. Catalona Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1498AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES PSA testing has limited performance characteristics for the diagnosis of prostate cancer (CaP). A promising possibility to improve PSA testing is to integrate a patient's genetic information. Recent studies have identified 4 genetic variants associated with increased PSA levels (Sci Trans Med 2010. 2(62):62). The increase risk of being diagnosed with CaP conferred by these variants may be mediated principally through their effects on increasing serum PSA levels. By correcting for the effects of these variants on PSA, it may be possible to create a personalized PSA cutoff that can better inform the decision to recommend a prostate biopsy. We therefore determined how many men would continue to meet common biopsy criteria after genetic PSA correction. METHODS The genotypes of 4 genetic variants associated with PSA levels (rs2736098, rs10788160, rs11067228, and rs17632542) were determined for 964 Caucasian healthy volunteers from 2003-2011. PSA values adjusted for genotype were calculated and weighted by dividing PSA values by their combined genetic risk, as previously described (Sci Trans Med). Statistical analyses were used to compare the percentage of men who would meet commonly-used PSA thresholds (>2.5 or 4.0ng/ml). RESULTS As an example, we determined the adjusted PSA for hypothetical men with genotypes for a variable number of PSA genetic variants (ranging from 0-4) and a PSA of 2.5ng/ml (Table 1). As demonstrated, the genetic PSA correction is weighted so that the adjusted PSA value decreases with the number of PSA variants carried. Significantly fewer men would be recommended to have a prostate biopsy after genetic adjustment (Table 2). For example, using 2.5 or 4.0 ng/ml as the biopsy threshold, genetic PSA correction would lead to a 15% and 20% relative reduction in potentially unnecessary biopsies, respectively. CONCLUSIONS Our results suggest that a personalized PSA value can be obtained by adjusting for the presence of 4 genetic variants that influence PSA levels. These values can be used to prevent unnecessary biopsies and improve the clinical performance characteristics of PSA. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e489 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brian T. Helfand Chicago, IL More articles by this author Stacy Loeb New York, NY More articles by this author Matthias D. Hofer Chicago, IL More articles by this author Dae Y. Kim Chicago, IL More articles by this author Qiaoyan Hu Chicago, IL More articles by this author Phillip R. Cooper Chicago, IL More articles by this author Barry B. McGuire Chicago, IL More articles by this author William J. Catalona Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The quantaflashTM chemiluminescent immunoassays for coeliac disease show excellent analytical and clinical performance characteristics

Objective Evaluate the analytical and clinical performances of four new chemiluminescent immunoassays developed for the random-access, automated BIO-FLASH® instrument for the diagnosis of coeliac disease (CD): IgA and IgG anti-human tissue transglutaminase (h-tTG) and anti-deamidated gliadin peptide (DGP). Methods The precision, limits of detection and linearity were determined following Clinical Laboratory and Standards Institute (CLSI) guidelines. Clinical sensitivities and specificities were determined using more than 700 subjects consisting of CD patients, healthy subjects, and patients with other diseases. Results The QUANTA Flash assays have larger dynamic ranges than ELISAs. The entire reportable range shows linearity for all four antibodies. The within-run, between-run and total % CVs in all four CD assays were less than 12.2%. The clinical sensitivities were 93%, 50%, 68% and 81% for h-tTG IgA, h-tTG IgG, DGP IgA and DGP IgG, respectively. The clinical specificities ranged from 98.0% to 99.6%. All tests have high diagnostic efficiency, characterised by areas under the curve values of 0.99, 0.93, 0.92, and 0.93 for h-tTG IgA, h-tTG IgG, DGP IgA and DGP IgG, respectively. Conclusion The new assays show excellent analytical performance characteristics. Their high clinical sensitivity and specificity make these tests invaluable for the diagnosis and management of coeliac disease patients. Evaluate the analytical and clinical performances of four new chemiluminescent immunoassays developed for the random-access, automated BIO-FLASH® instrument for the diagnosis of coeliac disease (CD): IgA and IgG anti-human tissue transglutaminase (h-tTG) and anti-deamidated gliadin peptide (DGP). The precision, limits of detection and linearity were determined following Clinical Laboratory and Standards Institute (CLSI) guidelines. Clinical sensitivities and specificities were determined using more than 700 subjects consisting of CD patients, healthy subjects, and patients with other diseases. The QUANTA Flash assays have larger dynamic ranges than ELISAs. The entire reportable range shows linearity for all four antibodies. The within-run, between-run and total % CVs in all four CD assays were less than 12.2%. The clinical sensitivities were 93%, 50%, 68% and 81% for h-tTG IgA, h-tTG IgG, DGP IgA and DGP IgG, respectively. The clinical specificities ranged from 98.0% to 99.6%. All tests have high diagnostic efficiency, characterised by areas under the curve values of 0.99, 0.93, 0.92, and 0.93 for h-tTG IgA, h-tTG IgG, DGP IgA and DGP IgG, respectively. The new assays show excellent analytical performance characteristics. Their high clinical sensitivity and specificity make these tests invaluable for the diagnosis and management of coeliac disease patients.

HPV molecular assays: Defining analytical and clinical performance characteristics for cervical cytology specimens

ObjectiveTo compare the analytical and clinical performance characteristics of 3 different primer sets targeting the human papillomavirus (HPV) L1 gene for detection and genotyping of HPV. MethodsLiquid-based cytology was obtained prospectively from 90 colposcopy clinic patients. After automated extraction, cellular DNA was subjected to SYBR Green quantitative polymerase chain reaction (qPCR) using GP5+/6+ primers and conventional PCR with MY09/11 and FAP59/64 primers. The resulting SYBR Green counts and melting temperatures (Tm) were used for quantification of HPV genomes and discrimination between presence and absence of amplicons. qPCR and PCR products were resolved by gel electrophoresis. HPV+amplicons were sequenced directly and BLAST® aligned for genotype identification. ResultsOf the 90 samples, 57 (63%) were qPCR+with a range of HPV viral load detected from 191 to 3.4million genomes (~5 Log10). Only HPV-positives exhibited characteristic Tm (75–80°C). The dynamic range of detection was similar for MY and FAP. Clinical net sensitivity was highest with simultaneous testing using all primer sets (93%) instead of individual primer pairs (GP (67%), MY (62%), FAP (49%)). Of the 27 HPV genotypes identified among 64 sequenced samples, the 3 most prevalent were HPV-16 (20%), −53 (9%), −31 (6%). The 4th rank included HPV-6, −33, −58, −66 (4.7% each). ConclusionThe performance characteristics of 3 leading PCR-based HPV assays revealed qPCR to be sensitive and specific for HPV detection and quantification. Parallel PCR testing using the 3 primers and direct sequencing offered the greatest clinical sensitivity and breadth of detection for known HPV types.

Clinical Experience Using the Mann Assessment of Swallowing Ability for Identification of Patients at Risk for Aspiration in a Mixed-Disease Population

To determine the clinical performance characteristics of the Mann Assessment of Swallowing Ability (MASA) for predicting aspiration (determined by videofluoroscopic swallowing study [VFSS]) in a mixed population. We selected 133 cases clinically evaluated using MASA and VFSS from January through June 2007. Ordinal risk rating (ORR) and total numeric score (TNS) were evaluated as predictors of aspiration on VFSS. To account for missing items, the maximum possible score was determined and a weighted percentage score calculated for each patient. We used receiver operating characteristic (ROC) analysis to compare the sensitivity and specificity of ORR and TNS for predicting aspiration. VFSS identified 51 (38.4%) aspirators, while ORR identified 54 (40.6%) as probable or definite aspiration and TNS 19 (14.3%) as moderate to severe aspiration risk. ROC analysis demonstrated an area under the curve of 0.74, 95% CI [0.66, 0.82], for ORR and 0.51, 95% CI [0.41, 0.61], for TNS. These ROC scores suggest that the MASA ORR is better at predicting aspiration on VFSS than the numeric score. In this sample, the subjective ORR had good predictive ability, while the percentage TNS failed to predict aspiration on VFSS. The MASA ORR assessment was a better predictor for a patient's aspiration risk in this population.

Clinical Value of Prognostic Instruments to Identify Patients with an Increased Risk for Osteoporotic Fractures: Systematic Review

BackgroundWith the broad availability of effective medications, identifying individuals bearing a higher risk for osteoporotic fractures has become an issue of major concern in modern medicine. In recent years various prognostic instruments have become available showing conflicting results regarding estimated risks for individual patients.ObjectiveTo provide an overview of current evidence and of opportunities for further research.Methodology/Principal FindingsSystematic Review: We identified studies describing the development of instruments and all subsequent validations in electronic databases and reference lists of included studies. We screened for inclusion, read full papers and extracted data on salient clinical features, performance characteristics and quality in duplicate. Searches retrieved 5,275 records of which full texts of 167 papers were obtained after screening titles and abstract. We included 35 studies enrolling a total of 609,969 patients (median 2546) reporting on 31 derivations and 12 validations after assessing full texts. Median follow-up time was 4.1 years (IQR 3 to 7.7). Only four studies validated an instrument that was developed by another group. None of the existing instruments was validated more than once. The five most frequent included variables in the final model were age, body mass index, bone mass index, past history of falls, and maternal history of fractures. The methodological quality of the studies was moderate.ConclusionThere is a plethora of evidence available studying the association of risk profiles and the development of osteoporotic fractures. The small number of out-of-sample validations, the large variety of study characteristics, outcomes and follow-up periods impedes from deriving robust summaries and from conclusions regarding the clinical performance of many tools. First and foremost, future activity in this field should aim at reaching a consensus among clinical experts in respect to the existing instruments. Then we call for careful validations and expedient adaptations for local circumstances of the most promising candidates.

Abstract 5231: Tilmaocept: A novel biotargeted agent for enhanced intraoperative discrimination of sentinel lymph nodes in breast cancer, melanoma, and head & neck SCC

Abstract Sentinel lymph node (SLN) mapping and identification is a primary component of surgical therapies for breast cancers, melanomas, pediatric soft tissue sarcomas, and certain other cancers. The current standard of care for identifying SLNs to inject into a tumor (or near a tumor) a blue dye (often called “vital blue dye”), of which several are available, in conjunction with a radiolabeled (99mTc) tracer, available as either a technetium sulfur colloid or as a technetium labeled albumin formulation. The exact formulations used vary, especially between those used in the United States and Europe. All such compounds are effectively agents of passive transport in the lymphatic ducts and are “inert” with regard to any biomarker recognition specificity. Allegedly, such agents move passively from the tumor/tumor basin into lymph nodes with a presumptive tumor-node anatomic nexus and the nodes are elucidated as blue and/or radioactive, the former based on excision line-of-sight, the latter based on intraoperative evaluation with a gamma-detecting probe. But because such components do not bear any specificity, that is, bind or accumulate lymph nodes bearing targets, they either remain static at the injection site and/or quickly drain away, reducing their real-time clinical effectiveness. A novel 99mTc-labeled, prospectively designed, low Mr molecule (99mTc DTPA Mannosyl Dextran; Tilmanocept) targeted as a ligand for the mannose binding receptor (MBR) of lymphatic reticuloendothelial cells and intended for real-time intraoperative gamma mapping of tumor-lymphatic nexuses has been synthesized and clinically tested in Phase 3 clinical studies in breast cancer and melanoma. The results of the development process and clinical testing indicate: 1) The prospective molecular designs resulted in safety and clinical performance characteristics that provided times from agent injection to patient evaluation that were significantly reduced compared to currently applied 99mTc-labeled agents; and 2) The specificity, sensitivity, and performance with regard to anatomic localization, false negative rates, and receptor retention exceed those of other colorimetric and 99mTc-labeled agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5231. doi:10.1158/1538-7445.AM2011-5231

Assessment of clinical and analytical performance characteristics of an HPV genotyping test

Human papillomavirus (HPV), the known cause of cervical cancer, is found in essentially all cervical cancer specimens. Infection with high-risk HPV genotypes carries the greatest risk of viral persistence and the potential to develop precancerous lesions or cervical cancer. Identifying women infected with HPV 16 and/or 18, the two genotypes most commonly found in cervical cancer, helps further stratify women for either immediate referral to colposcopy or repeat cytological and HPV DNA testing in 12 months. Genotyping additional, less carcinogenic HPV types may be of limited clinical utility. Detection of multiple individual genotypes may capture a greater percentage of those with the potential to develop cervical disease. However, the advantage of individual detection must be weighed against the potential error of multiple measurements. In order for genotyping tests to have clinical benefit in patient management, the Centers of Medicare and Medicaid Services Divisions of Laboratory Services have set forth a rigorous clinical validation procedure. This procedure addresses the quality process, characteristics and specifications of the assay, comparison of the test/device to existing tests/devices, technical aspects, and other assurances that guarantee the test/device will meet all performance requirements of the US Food and Drug Administration (FDA). Currently, only the Cervista® HPV 16/18 genotyping test is approved by the FDA and recommended for clinical use in published guidelines. This manuscript reviews the current best practices for the development and use of HPV genotyping tests.

Evaluation of a Rapid and Completely Automated Real-Time Reverse Transcriptase PCR Assay for Diagnosis of Enteroviral Meningitis

Nucleic acid amplification tests (NAATs) for enterovirus RNA in cerebrospinal fluid (CSF) have emerged as the new gold standard for diagnosis of enteroviral meningitis, and their use can improve the management and decrease the costs for caring for children with enteroviral meningitis. The Xpert EV assay (Cepheid, Sunnyvale, CA) is a rapid, fully automated real-time PCR test for the detection of enterovirus RNA that was approved by the U.S. Food and Drug Administration for in vitro diagnostic use in March 2007. In this multicenter trial we established the clinical performance characteristics of the Xpert EV assay in patients presenting with meningitis symptoms relative to clinical truth. Clinical truth for enteroviral meningitis was defined as clinical evidence of meningitis, the absence of another detectable pathogen in CSF, and detection of enterovirus in CSF either by two reference NAATs or by viral culture. A total of 199 prospectively and 235 retrospectively collected specimens were eligible for inclusion in this study. The overall prevalence of enteroviral meningitis was 26.04%. The Xpert EV assay had a sensitivity of 94.69% (90% confidence interval [CI] = 89.79 to 97.66%), specificity of 100% (90% CI = 99.07 to 100%), positive predictive value of 100%, negative predictive value of 98.17, and an accuracy of 98.62% relative to clinical truth. The Xpert EV assay demonstrated a high degree of accuracy for diagnosis of enteroviral meningitis. The simplicity and on-demand capability of the Xpert EV assay should prove to be a valuable adjunct to the evaluation of suspected meningitis cases.

Clinical Evaluation of a New Quantitative Enzyme-Linked Immunosorbent Assay for Anti-dsDNA Antibodies Measured in Patients With Systemic Lupus Erythematosus

The measurement of autoantibodies specific for double-stranded DNA (anti-dsDNA) is a useful tool for the diagnosis and prognosis of systemic lupus erythematosus (SLE). A quantitative enzyme-linked immunosorbent assay (ELISA) for anti-dsDNA antibodies has recently become available for the determination of anti-dsDNA antibodies. The aim of this study was to evaluate the clinical performance characteristics of this assay in patients with inactive or active SLE. Serum samples from patients with inactive (n=65) or active (n=112) SLE were tested for anti-dsDNA autoantibodies using 2 methods from Euroimmun AG (Lübeck, Germany)—a new ELISA anti-dsDNA assay and the currently available Crithidia luciliae indirect immunofluorescent test (CLIFT). In addition, the levels of the complement components C3 and C4 biological markers associated with SLE disease activity were measured by nephelometry in the sera from all patients. The sensitivity and specificity of the anti-dsDNA ELISA assay for discriminating between patients with inactive or active SLE were 93.54% and 67.69%, respectively. Among all patients (n=177), there was a weak concordance (κ=0.264) between anti-dsDNA results by the ELISA and CLIFT assay. However, a significant inverse correlation was found with complement components levels. In addition, area under the curve (AUC) values for anti-dsDNA as well as C3 and C4 assays decreased in the following order: 0.901 (ELISA for anti-dsDNA autoantibodies)>0.734 (C3)>0.723 (C4)>0.650 (CLIFT for anti-dsDNA autoantibodies). Our results show the ELISA for anti-dsDNA autoantibodies is significantly more sensitive and specific than any of the other assays we evaluated for discriminating between patients with inactive or active SLE. Moreover, the inverse correlation between ELISA anti-dsDNA autoantibody and complement levels suggests that anti-dsDNA results by the Euroimmun ELISA may be promising for monitoring disease activity in patients with SLE

Evaluation of a Newly Developed GenoArray Human Papillomavirus (HPV) Genotyping Assay and Comparison with the Roche Linear Array HPV Genotyping Assay

Persistent infection with high-risk types of human papillomavirus (HPV) is a necessary step in the development of cervical cancer. The incorporation of HPV detection into cervical screening programs may improve the ability to identify women at risk of cervical cancer. We recently evaluated the performance characteristics of a newly developed HPV detection assay, the GenoArray (GA) genotyping assay, for the detection of HPV infections by comparing it with the commercial Roche Linear Array (LA) HPV genotyping assay. The GA assay has an analytical sensitivity for the detection of HPV types 16 (HPV-16) and HPV-18 of as few as 10 to 50 copies, and its reproducibility is adequate. The GA and LA assays showed no significant difference in the rates of detection of genotypes detected by both HPV genotyping assays and oncogenic genotypes, and the interassay agreement was excellent. The GA and LA assays revealed either concordant or compatible genotyping results for 97.5% of the samples and discordant results for only eight (2.5%) samples. Compatible results were also observed for the detection of single or multiple HPV infections and the detection of most of the genotypes. The GA assay also demonstrated good clinical performance characteristics when the comparisons were carried out with clinical subgroups of samples from patients with normal cytologies, low-grade or high-grade squamous intraepithelial lesions, and cancers. Therefore, the GA assay appears to be highly sensitive and specific for the genotyping of HPV. It has the advantage that it specifically detects HPV-52, which overcomes a limitation of the LA assay, and hence, it has potential value for use for genotyping, especially in regions where HPV-52 has a high prevalence.

Clinical analysis of 50 cases with pulmonary inflammatory pseudotumor

Objective To explore the clinical diagnosis and surgical treatment of inflammatory pseudotumor of the lung. Methods From January 2002 to December 2008,the clinical data of 50 cases with pulmonary inflammatory pseudotumor were retospectively analyzed. Result 18 cases of preoperative diagnosis, the four cases of lobectomy, pulmonary wedge resection in 13 cases, and the rest are mass surgery, intraoperative tumor mostly see substantive, tumor visceral pleural surface without sag and shrinkage, tumor palpation There are hard and soft white felt, with incomplete tumor capsule, easily stripped. Resection of the pathological specimens were confirmed to be inflammatory pseudotumor, no operative complications and death in patients with follow-up 1～8 years, both curvived, without recurrence. Conclusion Inflammatory pseudotumor of their clinical performance and imaging characteristics of the lack of change in the low rate of preoperative diagnosis, surgical treatment of the main diagnostic, intraoperative frozen biopsy to determine pathology surgery, surgical approach to the limitations of pneumonectomy or lobectomy excision. Key words: Lung neoplasms; diagnosis

Recommended Principles and Practices for Validating Clinical Molecular Pathology Tests

The use of DNA- and RNA-based tests continues to grow for applications as varied as inherited disease, infectious disease, cancer, identity testing, human leukocyte antigen typing, and pharmacogenetics. Progress is driven in part by the huge growth in knowledge about the molecular basis of disease coupled with advancements in technologic capabilities. In addition to requirements for clinical utility, every molecular test also may have limitations that must be carefully considered before clinical implementation. Analytic and clinical performance characteristics as well as test limitations are established and documented through the process of test validation. To describe the established principles of test validation, along with relevant regulations in the United States, in order to provide a rational approach to introducing molecular tests into the clinical laboratory. PubMed review of published literature, published guidelines, and online information from national and international professional organizations. These resources and recommendations provide a framework for validating clinical tests.

Detection of Cytomegalovirus in Whole Blood Using Three Different Real-Time PCR Chemistries

Several different primer-probe chemistries have been produced commercially for real-time PCR detection and quantification of cytomegalovirus, but there are few studies evaluating their relative performance. We assessed three such commercial reagents with respect to analytical and clinical operating characteristics. The samples included 149 clinical whole blood specimens that were de-identified and assayed in parallel with all primer-probe systems. Individual methods used TaqMan, dual fluorescence resonance energy transfer hybridization probes, and labeled primer chemistries. Method comparability was determined both qualitatively, based on pair-wise assessment of concordance, and quantitatively, based on pair-wise linear regression analysis. Analytical sensitivity and the lower end of the linear dynamic range reached 10 target copies per reaction for the TaqMan and labeled primer systems and 100 target copies per reaction for the dual fluorescence resonance energy transfer probe system. Quantitative linearity reached an upper limit of 10(5) copies per reaction for all methods. No assay cross-reactivity was seen with other common viral pathogens (100% analytical specificity). Pair-wise analysis of qualitative results from clinical samples showed no significant differences in sensitivity between the three sets of reagents, and linear regression analysis indicated that the quantitative values achieved were comparable in all positive specimens. The findings demonstrate that similar analytical and clinical performance characteristics can be demonstrated for quantitative detection of cytomegalovirus in clinical whole blood extracts using a wide variety of real-time PCR chemistries.

Evidence-based laboratory medicine. Application in autoimmunity

Concepts of evidence based laboratory medicine are increasingly utilised in routine clinical and laboratory practice. Some basic concepts of evidence based laboratory medicine, such as likelihood ratios, are not fully comprehended by laboratory professionals and clinicians. This lecture aims to make laboratory professionals and clinicians more familiar with the basic concepts that deal with clinical performance characteristics of a laboratory test. Basic measures of the clinical performance characteristics of a laboratory test, such as sensitivity, specificity, likelihoods, likelihood ratio, post-test probability, odds, and Bayes theorem will be explained. The concepts will be illustrated with serological markers for autoimmune diseases (anti-tissue transglutaminase, anti-CCP antibodies, ASCA, anti-neutrophil cytoplasmic antibodies). The lecture seeks to provide the audience with a better understanding of the clinical performance characteristics of a laboratory test and of evidence-based laboratory medicine. Concepts of evidence based laboratory medicine are increasingly utilised in routine clinical and laboratory practice. Some basic concepts of evidence based laboratory medicine, such as likelihood ratios, are not fully comprehended by laboratory professionals and clinicians. This lecture aims to make laboratory professionals and clinicians more familiar with the basic concepts that deal with clinical performance characteristics of a laboratory test. Basic measures of the clinical performance characteristics of a laboratory test, such as sensitivity, specificity, likelihoods, likelihood ratio, post-test probability, odds, and Bayes theorem will be explained. The concepts will be illustrated with serological markers for autoimmune diseases (anti-tissue transglutaminase, anti-CCP antibodies, ASCA, anti-neutrophil cytoplasmic antibodies). The lecture seeks to provide the audience with a better understanding of the clinical performance characteristics of a laboratory test and of evidence-based laboratory medicine.

Rapid Group B Streptococci Screening Using a Real-Time Polymerase Chain Reaction Assay

To estimate the clinical performance characteristics of a real-time polymerase chain reaction (PCR) assay using vaginal/rectal swabs from antepartum (35-37 weeks of gestation) and intrapartum women. The assay evaluated is a qualitative, automated, real-time PCR test for the detection of group B streptococci, with results available in approximately 75 minutes. Enrollment in this multicenter clinical study occurred between October 2005 and January 2006. Vaginal/rectal swabs were analyzed by nursing personnel (intrapartum tests) or by laboratory technologists (all others). Polymerase chain reaction assay results were compared with culture using standard methods, including selective broth medium, and to a predicate nucleic acid amplification test. Of 1,028 enrolled women, 234 were deemed ineligible, and 10 had unresolved test results. Of the 784 remaining women, valid PCR assay results were obtained on the first test attempt for 93.0%. Performance characteristics relative to culture were sensitivity 91.1%, specificity 96.0%, positive predictive value 87.8%, negative predictive value 97.1%, and accuracy 94.8%. These results exceeded those obtained using the predicate nucleic acid amplification test. Performance characteristics of the PCR assay exceed the threshold recommended by the Centers for Disease Control and Prevention when compared with culture. The test is sufficiently robust to be performed for intrapartum patients in a point-of-care setting by medical professionals. II.

Clinical performance and wear characteristics of veneered lithia-disilicate-based ceramic crowns

Objectives The objectives of this study were to characterize the clinical performance and wear characteristics of lithia-disilicate-based ceramic crowns. Methods Thirty posterior crowns were made using the heat-pressing technique and lithia-disilicate-based core ceramic. Subjects were recalled annually. The quality of crowns and adjacent gingival tissues were examined using nine criteria for acceptability. All crowns were examined and ranked from 4 (Excellent) to 1 (Unacceptable) for each criterion. Impressions were made for replica models at each appointment. Wear characteristics of dental ceramic and enamel were obtained by comparing the surface of the original model with the follow-up model using a laser scanner. Results Twenty-nine subjects returned for the 1-year recall examination. The maximum clenching force for the 30 subjects ranged from 125 to 815 N. All clinical criteria were ranked good to excellent at the 1-year recall exam and no fractures were observed. The mean occlusal wear volumes for the ceramic crowns after 1 year were 0.19 (0.065) mm 3 for premolar sites and 0.34 (0.08) mm 3 for molar sites. The mean occlusal wear volumes of opposing enamel after 1 year were 0.21 (0.06) mm 3 for premolar teeth and 0.50 (0.22) mm 3 for molar teeth. The mean occlusal wear volume of ceramic molar crowns was significantly lower than the volume of enamel wear of the opposing teeth ( p ≤ 0.05). Conclusions The quality of the overall prostheses and the gingival tissues were acceptable after 1 year. The mean occlusal wear volume of ceramic molar crowns was significantly lower than the enamel wear volume of the opposing teeth.

A Novel Use of Radar Graphs in Evaluating the Operational Performance Characteristics of Laboratory Instruments

The evaluation of new laboratory instruments as potential replacements for existing instruments occurs frequently in most clinical laboratories. Typically, considerable attention is paid to the evaluation of the analytical performance characteristics (eg, precision, accuracy, reportable range, reference interval) of the methods for the various analytes that can be quantified using these instruments, some or no attention is paid to the clinical performance characteristics [eg, diagnostic accuracy (sensitivity and specificity), negative and positive predictive value] of these methods, and little attention may be paid to the operational performance characteristics (eg, acceptable specimen types and volume requirements, completeness of test menu, maximum run size) of the new instrument compared to the existing or competitor instruments. The rationale for this difference in attention paid by laboratory professionals to the aforementioned performance characteristics of laboratory methods/instruments is most likely

Diagnostic accuracy of coeliac serological tests: a prospective study

The best way to test serologically for coeliac disease (CD) remains controversial, with endomysial (EMA), transglutaminase (TTG), and gliadin antibodies (AGA) being assessed in various combinations with no apparent standardization. The objective of this study was to evaluate whether TTG-IgA+/-TTG-IgG could be used as a replacement for endomysial antibodies as a reliable screen for CD in patients presenting to a major Australian tertiary referral hospital for assessment of symptoms consistent with CD. Individuals referred for gastroscopic assessment of possible CD were prospectively evaluated by duodenal biopsy assessment. The following diagnostic methods were compared: dual-isotype transglutaminase (TTG-dual), combined-isotype transglutaminase (TTG-IgA+G), TTG-IgA, combined-isotype gliadin antibodies (AGA-IgA+G), AGA-IgA, and endomysial antibody assays. Clinical performance characteristics (sensitivity, specificity, area under the curve for receiver-operating characteristic analysis; AUROC) were assessed for all kits. The correlation between transglutaminase kits was generally good, with the best transglutaminase kit demonstrating high correlation (r=0.86) with endomysial antibodies. A comparison of different types of endomysial antibody assays displayed variable diagnostic performance (sensitivity 61.90-68.42%; specificity 80.00-98.57%; AUROC 0.71-0.83). Sensitivity (90.48-92.31%), specificity (80.77-82.89%) and AUROC values (0.92-0.94) for dual-isotype transglutaminase kits displayed narrow ranges. AGA assays were less sensitive (AGA-IgA: 42.31-46.15%; AGA-IgG: 61.54%) and less specific (AGA-IgA: 85.09-87.73%; AGA-IgG: 82.46-84.09%). Dual-isotype transglutaminase testing was diagnostically equivalent to transglutaminase-IgA (AUROC 0.92 versus 0.91, P=0.33). Our study suggests that transglutaminase screening (using the IgA+/-IgG isotype) is a sensitive and specific alternative to endomysial antibody testing in the serological assessment of CD. On the basis of our findings, AGA antibody testing no longer appears to be an essential part of the diagnostic strategy for adult CD.

Prostate-specific antigen: bias and molarity of commercial assays for PSA in use in England

The UK Prostate Cancer Risk Management Programme has recommended that all assays for prostate-specific antigen (PSA) should be both equimolar in their response to free and complexed PSA and calibrated to the World Health Organization (WHO) First International Standard for PSA (90:10). To determine which assays currently being used by diagnostic laboratories in England fulfil these criteria, a PSA recovery experiment was performed. In all, 15 samples containing varying mixtures and concentrations of the WHO International Standards for PSA and free PSA were sent to 223 laboratories in England who participate in the UK National External Quality Assessment Service (UK NEQAS) scheme for analysis. Analytical platforms were assigned to one of 11 methods, and the results were converted into recovery percentages and analysed by means of a linear random intercept model. No method was both unbiased and equimolar; estimates of bias ranged from -5% to 22% and estimates of non-equimolarity (change in bias per percent increase in free PSA) ranged from -0.18% to 0.28%. Analytical methods currently in use for PSA in England have inter-method differences; some methods have estimated biases over 10% which can result in unacceptable clinical performance characteristics. Methods for PSA should be equimolar and calibrated to the international standard to minimize the likelihood of clinical errors.

Analytical and clinical evaluation of the Bayer ADVIA Centaur automated B-type natriuretic peptide assay in patients with heart failure: a multisite study.

B-Type natriuretic peptide (BNP) is released from the left ventricle of the heart into the circulation in response to ventricular stretching and volume overload. Increased BNP concentrations are associated with heart failure (HF). We evaluated the analytical and clinical performance of the Bayer ADVIA Centaur BNP assay. Studies included precision, analytical correlation (against the Shionogi ShionoRIA and Biosite Triage BNP assays), BNP results for blood collected in plastic tubes containing EDTA vs other collection tubes, high-dose hook effect, detection limits, and interferences. The clinical performance was tested on 2243 blood samples collected from 983 apparently healthy individuals, 538 patients with chronic disease but without HF (renal insufficiency, chronic obstructive pulmonary disease, diabetes, and hypertension), and 722 patients with HF (New York Heart Association classes I-IV). The ADVIA Centaur assay had total imprecision (CV) of 3.4%, 2.9%, and 2.4% at BNP concentrations of 48, 461, and 1768 ng/L, respectively. The Passing-Bablok correlations to the ShionoRIA and Triage were as follows: ADVIA Centaur = 1.11(ShionoRIA) - 1.19 ng/L (r = 0.98); ADVIA Centaur = 0.78(Triage) + 5.89 ng/L (r = 0.92), respectively. Of the different blood collection tubes, only EDTA plastic tubes (with and without the barrier gel) were acceptable. The lower detection limit was 0.5 ng/L, and there were no interferences from common analytes, other neuropeptides, or unusual antibodies. BNP exhibited different reference intervals according to age and gender. BNP concentrations increased progressively as the severity of HF increased. The ADVIA Centaur is the first commercially available BNP assay for use on an automated immunochemistry platform. This assay has good analytical and clinical performance characteristics for diagnosing HF.