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False-positive
Terms modified by False-positive Selected AbstractsUnderdiagnosis of Vertebral Fractures Is a Worldwide Problem: The IMPACT StudyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2005Pierre D Delmas MD Abstract Accurate radiographic diagnosis of vertebral fractures is important. This multicenter, multinational study assessed radiographic diagnoses of vertebral fracture in 2451 postmenopausal women with osteoporosis. Comparison between local and central readings yielded a false-negative rate of 34%. Underdiagnosis of vertebral fracture is a worldwide problem. Introduction: Vertebral fractures are the most common complication of osteoporosis. Although they are associated with significant morbidity, they frequently do not come to clinical attention. Accurate radiographic diagnosis is important. Materials and Methods: In a multicenter, multinational prospective study (the IMPACT trial), the accuracy of radiographic diagnosis of vertebral fracture was evaluated in postmenopausal women 65,80 years of age newly diagnosed with osteoporosis (based on BMD measurement). Lateral radiographs of the thoracolumbar spine were evaluated for identification of vertebral fractures, first locally and subsequently at a central reading center, using a validated semiquantitative method. False-positive and false-negative rates were calculated based on adjudicated discrepancies between the initial interpretation at the local site and the subsequent central reading, considered the "reference standard." Results: Of 2451 women with an evaluable radiograph both centrally and locally, 789 (32%) had at least one vertebral fracture. Adjudicated discrepancies (n = 350 patients) between local and central readings because of undetected vertebral fracture (68%) or equivocal terminology in the local radiology report (32%) yielded a false-negative rate of 34%. Conclusions: Underdiagnosis of vertebral fractures was observed in all geographic regions (false-negative rates: North America, 45.2%; Latin America, 46.5%; Europe/South Africa/Australia, 29.5%). The false-positive rate was 5% globally. Underdiagnosis of vertebral fracture is a worldwide problem attributable in part to a lack of radiographic detection, use of ambiguous terminology in the radiology report, or both. Efforts to improve accuracy and reduce variability in terminology and interpretation may increase the effectiveness of spinal radiography for detecting vertebral fractures in patients with osteoporosis. [source] False-positive liquid chromatography/tandem mass spectrometric confirmation of sebuthylazine residues using the identification points system according to EU directive 2002/657/EC due to a biogenic insecticide in tarragonRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 8 2009Andreas Schürmann In pesticide residue analysis using liquid chromatography/tandem mass spectrometry (LC/MS/MS) the confirmation of a sebuthylazine finding in a tarragon (Artemisia dranunculus) sample was demonstrated to be false positive. A coeluting interfering matrix compound produced product ions in MS/MS analysis, perfectly corresponding to the multiple reaction monitoring (MRM) of two sebuthylazine transitions. Using the EU directive 2002/657/EC which regulates the confirmation of suspected positive findings would have resulted in a false-positive finding. A third LC/MS/MS transition with a deviant ion ratio and a gas chromatography (GC)/MS/MS analysis revealed the false-positive results. With optimized high resolving ultra-performance liquid chromatography (UPLC) conditions it was possible to separate spiked sebuthylazine from the interfering matrix compound. Using its exact mass and isotope ratios from LC/time-of-flight (TOF) MS measurements, the compound was identified as nepellitorine, a , not surprising , endogenous alkamide in tarragon (Arthemisia dranunculus). False-positive results, especially in heavy matrix samples such as herbs, can be dealt with by further confirmatory analysis, e.g. a third transition, GC analysis if possible or more advantageous by an orthogonal criterion like exact mass. Copyright © 2009 John Wiley & Sons, Ltd. [source] A comparison of urinary nuclear matrix protein-22 and bladder tumour antigen tests with voided urinary cytology in detecting and following bladder cancer:the prognostic value of false-positive resultsBJU INTERNATIONAL, Issue 7 2001V. Poulakis Objectives To evaluate the diagnostic and prognostic value of the nuclear matrix protein-22 (NMP22) and bladder tumour antigen (BTAstat) tests compared with voided urinary cytology (VUC) in detecting and following bladder cancer, assessing particularly the prognostic value of false-positive test results in patients followed up for bladder cancer. Patients and methods From 739 patients suspected of having bladder cancer, voided urine samples for the NMP22 and BTAstat tests, and for VUC and urine analysis, were collected before cystoscopy. All patients underwent transurethral resection of bladder lesions or mapping, and were followed for a mean (range) of 27.3 (3,65) months. Results In the 406 patients with bladder cancer, the overall sensitivity was 85% for NMP22, 70% for BTAstat and 62% for VUC. For histological grades 1,3 the sensitivity in detecting transitional cell carcinoma was 82%, 89% and 94% for NMP22, 53%, 76% and 90% for BTAstat, and 38%, 68% and 90% for VUC, respectively. Although the sensitivity in detecting invasive carcinoma was > 85% for all the tests, NMP22 and BTAstat were statistically more sensitive than VUC for superficial tumours. The optimal threshold value for NMP22, calculated using the receiver operating characteristics curve, was 8.25 U/mL. The specificity was 68% for NMP22, 67% for BTAstat, and 96% for VUC. The specificity of VUC remained > 87% and was independent of benign histological findings. In contrast, in patients with no apparent genitourinary disease on histology, NMP22 and BTAstat had significantly higher specificity (94% and 92%, respectively; P = 0.003) than in the group with chronic cystitis (52% for both tests). Forty patients having no bladder cancer at biopsy had a recurrence after a mean (range) follow-up of 7.7 (3,15) months; all had a previous history of bladder cancer. According to subsequent recurrence, the prognostic positive and negative predictive values were 18% and 91% for NMP22, 13% and 88% for BTAstat, and 79% and 91% for VUC. Both false-positive VUC and NMP22 tests predicted recurrence (log-rank test, P < 0.001 and P = 0.004, respectively), but the BTAstat test produced no similar correlation (P = 0.778). Conclusion The NMP22 and BTAstat tests are better than VUC for detecting superficial and low-grade bladder cancer but they have significantly lower specificity. After excluding diseases with the potential to interfere in these tests the overall specificity of both tests is increased considerably. False-positive results from NMP22 and VUC but not from BTAstat in patients followed up for bladder cancer correlate with future recurrences. [source] Formaldehyde-releasers: relationship to formaldehyde contact allergy.CONTACT DERMATITIS, Issue 2 2009Contact allergy to formaldehyde, inventory of formaldehyde-releasers This is one of series of review articles on formaldehyde and formaldehyde-releasers (others: formaldehyde in cosmetics, in clothes and in metalworking fluids and miscellaneous). Thirty-five chemicals were identified as being formaldehyde-releasers. Although a further seven are listed in the literature as formaldehyde-releasers, data are inadequate to consider them as such beyond doubt. Several (nomenclature) mistakes and outdated information are discussed. Formaldehyde and formaldehyde allergy are reviewed: applications, exposure scenarios, legislation, patch testing problems, frequency of sensitization, relevance of positive patch test reactions, clinical pattern of allergic contact dermatitis from formaldehyde, prognosis, threshold for elicitation of allergic contact dermatitis, analytical tests to determine formaldehyde in products and frequency of exposure to formaldehyde and releasers. The frequency of contact allergy to formaldehyde is consistently higher in the USA (8,9%) than in Europe (2,3%). Patch testing with formaldehyde is problematic; the currently used 1% solution may result in both false-positive and false-negative (up to 40%) reactions. Determining the relevance of patch test reactions is often challenging. What concentration of formaldehyde is safe for sensitive patients remains unknown. Levels of 200,300 p.p.m. free formaldehyde in cosmetic products have been shown to induce dermatitis from short-term use on normal skin. [source] Respiratory cytology: Differential diagnosis and pitfallsDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2010F.R.C.P.C., Ph.D., Reda S. Saad M.D. Abstract Pulmonary cytology can be challenging and has its share of diagnostic pitfalls. Reactive atypia can occasionally be alarming, leading to diagnostic pitfall for a false-positive diagnosis of malignancy, even for experienced cytopathologists (Naryshkin and Young, Diagn Cytopathol 1993;9:89,97). In addition, cytologic preparations can show an absence of architectural clues, leading to diagnostic difficulties. Some conditions can cytologically as well as clinically and radiographically mimic malignancies, making these pitfalls even more frequent (Bedrossian et al., Lab Med 1983;14:86,95). A recent report stated that "no laboratory that aims to make definitive diagnoses in pulmonary cytology can be spared from false-positive results"(Policarpio-Nicolas and Wick, Diagn Cytopathol 2008;36:13,19). A false-positive finding could produce unnecessary treatment and morbidity, whereas false-negative diagnosis could result in delayed diagnosis and treatment. This review analyzes and illustrates cellular changes and benign entities that can mimic malignancy in respiratory cytology as well as neoplasms that could lead to a false-negative diagnosis. In addition, some specific challenging and difficult aspects in classification of pulmonary malignancies will be discussed. Guidelines and clues are presented to avoid such pitfalls. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] Bone lesions: Role of sediment cytologyDIAGNOSTIC CYTOPATHOLOGY, Issue 6 2009Surbhi Shah M.B.B.S. Abstract This study was conducted to evaluate the role of sediment cytology of biopsy specimen fixatives, which is usually discarded, in early diagnosis of bone lesions. Cytological smears prepared from sediments of biopsy specimen fixatives (sediment cytology) were used to study 65 bone specimens biopsied with suspicion of malignancy. The cytological diagnosis was then compared with histological diagnosis, taking the latter as gold standard. Smears were adequately cellular and showed good preservation of cellular morphology. Some of the smears showed microfragments of tissue. Cytology labeled 29 lesions as malignant, 26 lesions as benign, 3 as inflammatory, and 7 smears as inconclusive because of low cell yield. Sediment cytology was able to correctly diagnose 58 of 65 lesions. There was no false-positive or false-negative case. The sediment cytology could be considered as an easy and effective diagnostic tool that can provide early diagnosis for the lesion of bone. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Impact of Valvular Calcification on the Diagnostic Accuracy of Transesophageal Echocardiography for the Detection of Congenital Aortic Valve MalformationECHOCARDIOGRAPHY, Issue 7 2007Akash Makkar M.D. Background: Degeneration of congenital bicuspid or unicuspid aortic valves can progress more rapidly than that of tricuspid valves, and an early diagnosis significantly impacts decision making and outcome. We hypothesized that the extent of valvular calcification would negatively influence the diagnostic accuracy of multiplane transesophageal echocardiography (TEE) for the diagnosis of congenital aortic valve disease. Methods: TEE was performed in 57 patients undergoing aortic valve replacement surgery for aortic stenosis (n = 46), pure regurgitation (n = 9), or significant regurgitation with less than severe aortic stenosis (n = 2). The degree of aortic valve calcification and the number of valve cusps were determined at surgery. Results: Surgical inspection confirmed 14 bicuspid and 43 tricuspid aortic valves. Sensitivity and specificity of TEE for the diagnosis of congenital aortic valve malformation was 93% (13/14) and 91% (39/43) (P = 0.0001), respectively. In patients with no or mild aortic valve calcification (n = 13), sensitivity and specificity of TEE for the diagnosis of congenitally malformed aortic valve was 100% (5/5) and 100% (8/8) (P = 0.001), respectively. In patients with moderate or marked aortic valve calcification (n = 44), sensitivity and specificity of TEE for the diagnosis of congenitally malformed aortic valve was 89% (8/9) and 89% (31/35) (P<0.0001), respectively. In this subgroup of 44 patients, there were four false-positive and one false-negative diagnoses due to valvular calcification. Conclusions: Although TEE is highly sensitive and specific for the detection of congenital aortic valve malformations, presence of moderate or marked calcification of the aortic valve may result in false positive and false negative diagnoses. [source] Gene,environment interactions and alcohol use and dependence: current status and future challengesADDICTION, Issue 6 2009Carmen S. Van Der Zwaluw ABSTRACT Aim To discuss the current status of gene,environment interaction research with regard to alcohol use and dependence. Further, we highlight the difficulties concerning gene,environment studies. Methods Overview of the current evidence for gene,environment interactions in alcohol outcomes, and of the associated challenges in gene,environment studies. Results Attention to the causative roles of gene,environment interactions in alcohol use and dependence is increasing. Studies with twin designs are beginning to examine gene-shared environment effects, and animal studies have investigated gene,environment interaction effects on alcohol intake in primates. Thirteen studies incorporated gene,environment interactions in examining alcohol use or dependence in humans. These studies held a variety of candidate genes and environmental risk factors and their heterogeneity made it impossible to draw firm general conclusions. Conclusions Challenges for future gene,environment studies are abundant, and consist of, for example, the development of clear theoretical assumptions about neurobiological mechanisms and the recruitment of large longitudinal samples that already start in childhood. Replication is essential to prevent an overload of false-positive results. Despite the difficulties, it is crucial to include gene,environment interactions in future studies in order to unravel the aetiological factors of human alcohol outcomes. [source] Is my antibody-staining specific?EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008How to deal with pitfalls of immunohistochemistry Abstract Immunohistochemistry is a sensitive and versatile method widely used to investigate the cyto- and chemoarchitecture of the brain. It is based on the high affinity and selectivity of antibodies for a single epitope. However, it is now recognized that the specificity of antibodies needs to be tested in control experiments to avoid false-positive results due to non-specific binding to tissue components or recognition of epitopes shared by several molecules. This ,Technical Spotlight' discusses other pitfalls, which are often overlooked, although they can strongly influence the outcome of immunohistochemical experiments. It also recapitulates the minimal set of information that should be provided in scientific publications to allow proper evaluation and replication of immunohistochemical experiments. In particular, tissue fixation and processing can have a strong impact on antigenicity by producing conformational changes to the epitopes, limiting their accessibility (epitope masking) or generating high non-specific background. These effects are illustrated for an immunoperoxidase staining experiment with three antibodies differing in susceptibility to fixation, using tissue from mice processed under identical conditions, except for slight variations in tissue fixation. In these examples, specific immunostaining can be abolished depending on fixation strength, or detected only after prolonged postfixation. As a consequence, antibody characterization in immunohistochemistry should include their susceptibility towards fixation and determination of the optimal conditions for their use. [source] Detection of marginal defects of composite restorations with conventional and digital radiographsEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2002Rainer Haak The purpose of this study was to determine the validity of detecting approximal imperfections of composite fillings using three intraoral radiographic systems in vitro. Class II composite resin restorations (108) with three radiopacities (264, 306, 443% Al 99.5) of which 27 had marginal openings or overhangs, respectively, were conventionally (Ektaspeed plus) and digitally (Dexis, Digora) radiographed. Images were assessed by 10 observers for the presence of marginal gaps and overhangs, as well as for their need of restorative treatment according to a five-point confidence rating scale. The validity of the observations were expressed as areas under receiver operating characteristic (ROC) curves (Aroc). Repeated measures analysis of variance revealed significant effects of ,radiographic system' and ,diagnostic purpose'. Marginal overhangs (Aroc = 0.90) were significantly easier to diagnose than openings (Aroc = 0.63). Marginal gaps were better detected on conventional and Dexis radiographs than on Digora images. the range of sensitivities and specificities of the treatment decision was 0.53,0.56 and 0.87,0.88, respectively. It was concluded that the validity of detecting marginal defects of composite resin restorations based on radiographs was only slightly affected by the radiographic system being used. The diagnosis of marginal gaps frequently resulted in false-positive and false-negative decisions. [source] Case-control association testing in the presence of unknown relationshipsGENETIC EPIDEMIOLOGY, Issue 8 2009Yoonha Choi Abstract Genome-wide association studies result in inflated false-positive results when unrecognized cryptic relatedness exists. A number of methods have been proposed for testing association between markers and disease with a correction for known pedigree-based relationships. However, in most case-control studies, relationships are generally unknown, yet the design is predicated on the assumption of at least ancestral relatedness among cases. Here, we focus on adjusting cryptic relatedness when the genealogy of the sample is unknown, particularly in the context of samples from isolated populations where cryptic relatedness may be problematic. We estimate cryptic relatedness using maximum-likelihood methods and use a corrected ,2 test with estimated kinship coefficients for testing in the context of unknown cryptic relatedness. Estimated kinship coefficients characterize precisely the relatedness between truly related people, but are biased for unrelated pairs. The proposed test substantially reduces spurious positive results, producing a uniform null distribution of P -values. Especially with missing pedigree information, estimated kinship coefficients can still be used to correct non-independence among individuals. The corrected test was applied to real data sets from genetic isolates and created a distribution of P -value that was close to uniform. Thus, the proposed test corrects the non-uniform distribution of P -values obtained with the uncorrected test and illustrates the advantage of the approach on real data. Genet. Epidemiol. 33:668,678, 2009. © 2009 Wiley-Liss, Inc. [source] Haplotype analysis in the presence of informatively missing genotype dataGENETIC EPIDEMIOLOGY, Issue 4 2006Nianjun Liu Abstract It is common to have missing genotypes in practical genetic studies, but the exact underlying missing data mechanism is generally unknown to the investigators. Although some statistical methods can handle missing data, they usually assume that genotypes are missing at random, that is, at a given marker, different genotypes and different alleles are missing with the same probability. These include those methods on haplotype frequency estimation and haplotype association analysis. However, it is likely that this simple assumption does not hold in practice, yet few studies to date have examined the magnitude of the effects when this simplifying assumption is violated. In this study, we demonstrate that the violation of this assumption may lead to serious bias in haplotype frequency estimates, and haplotype association analysis based on this assumption can induce both false-positive and false-negative evidence of association. To address this limitation in the current methods, we propose a general missing data model to characterize missing data patterns across a set of two or more markers simultaneously. We prove that haplotype frequencies and missing data probabilities are identifiable if and only if there is linkage disequilibrium between these markers under our general missing data model. Simulation studies on the analysis of haplotypes consisting of two single nucleotide polymorphisms illustrate that our proposed model can reduce the bias both for haplotype frequency estimates and association analysis due to incorrect assumption on the missing data mechanism. Finally, we illustrate the utilities of our method through its application to a real data set. Genet. Epidemiol. 2006. © 2006 Wiley-Liss, Inc. [source] Accuracy of 18F-FDG-PET/CT for staging of oral squamous cell carcinoma,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2008MSci, Monica Pentenero DDS Abstract Background. This study prospectively assessed 2-[F18]-fluoro-2-deoxy- D -glucose,positron emission tomography (18F-FDG-PET)/CT (PET/CT) in oral squamous cell carcinoma. Methods. Twenty-three patients completed preoperative TNM staging (CT, MR, whole-body fusion imaging PET/CT). In patients who underwent surgical therapy (19 of 23), TNM staging based on PET/CT scan was compared with pTNM. Results. PET/CT correctly staged 16 of 19 primary tumors (accuracy 84.2%, sensitivity 84.2%, positive predictive value 100%) and correctly ruled out bone invasion in 3 patients with false-positive results according to CT and/or MR. PET/CT incorrectly identified neck involvement in 5 of 15 patients (3 false positives, 2 false negatives) who underwent neck dissection (accuracy 66.7%, specificity 76.9%, negative predictive value 83.3%). False-negative cases showed a nodal size not exceeding 10 mm. One patient with a bronchial synchronous primary tumor was identified. Conclusion. PET/CT scan showed good accuracy in determining the extension and/or depth of invasion of the primary tumor. Nevertheless, PET/CT was not accurate to rule out nodal metastases. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] The value of frozen section in intraoperative surgical management of thyroid follicular carcinoma,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2003Danijel Do, en MD Abstract Background. Preoperative and intraoperative diagnosis of follicular carcinoma (FC), resulting in one-stage surgical treatment of follicular thyroid tumors, is an important issue in thyroid surgery. Methods. In the 10-year period there were 4158 operations performed on thyroid gland. There were 1559 patients with follicular tumors, 70 (4.4%) of them having FC. We analyzed the groups of patients with FC determined on frozen section (FS) and permanent section (PS) according to duration of clinical symptoms, ultrasound (US) examination, tumor size, patient gender and age, intensity of invasion, localization, and multiple or solitary occurrence of tumor. Results. FC was diagnosed in 39 (55.7%) patients on frozen section (FS). Among the encapsulated (minimal invasion) carcinomas, the FS was accurate in 19 of 33 (57.6%) FC and in 5 of 15 (27.8%) Hürthle cell carcinomas (HCC); among extensively invasive carcinoma in 11 of 14 (78.6%) FC and in 4 of 5 (80.0%) HCC. FC was significantly more common in men (p < .001) and in the right lobe (p < .05). We did not find statistically significant differences concerning duration of symptoms, US examination, tumor size, patient age, and multiple or solitary occurrence of the tumor between the patients with FC diagnosed on FS and the patients with FC diagnosed on PS. Conclusions. The intraoperative diagnosis of FC is difficult. Although the percentage of false-negative results was relatively high (44.3%), there were no false-positive results. This means that the second operation was avoided in 55.7% of the patients, and no unnecessary thyroidectomies were performed. FS biopsy is an important method in surgery of follicular tumors. Improved technical support and the ability to analyze a greater number of slides will increase the accuracy of the method. © 2003 Wiley Periodicals, Inc. Head Neck 25: 521,528, 2003 [source] F-18-fluoro-deoxy-glucose positron-emission tomography scanning in detection of local recurrence after radiotherapy for laryngeal/ pharyngeal cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2001Chris H. Terhaard MD Abstract Background The objective of this investigation was to determine whether F18-fluoro-deoxy-glucose (FDG) positron-emission tomography (PET) could differentiate between local recurrence and late radiation effects after radiotherapy for laryngeal/pharyngeal cancer. Methods In a prospective study of 75 patients (67 larynx, eight oro/hypopharynx), 160 laryngoscopies and 109 FDG PET scans were performed on the head and neck region. The mean follow-up time after the first FDG PET scan was 23 months (minimum 1 year). Results Local recurrence was diagnosed in 37 patients: 19 after the first biopsy and 18 after follow-up biopsies. For all of the negative initial FDG scans (27), the biopsies that were taken at the same time were negative and no recurrence was seen for at least 1 year. The first FDG scan was a true positive in 34 of 48 patients. In 12 of the 14 patients with false-positive results, FDG scans were repeated; a decreased FDG uptake was found in 9 of the 12. The sensitivity and specificity of the first scan were respectively 92% and 63%; including subsequent FDG scans, the rates were 97% and 82%, respectively. Conclusions When a local recurrence is suspected after radiotherapy for cancer of the larynx/pharynx, an FDG PET scan should be the first diagnostic step. No biopsy is needed if the scan is negative. If the scan is positive and the biopsy negative, a decreased FDG uptake measured in a follow-up scan indicates that a local recurrence is unlikely. © 2001 John Wiley & Sons, Inc. Head Neck 23: 933,941, 2001. [source] A panel of ancestry informative markers for estimating individual biogeographical ancestry and admixture from four continents: utility and applications,HUMAN MUTATION, Issue 5 2008Indrani Halder Abstract Autosomal ancestry informative markers (AIMs) are useful for inferring individual biogeographical ancestry (I-BGA) and admixture. Ancestry estimates obtained from Y and mtDNA are useful for reconstructing population expansions and migrations in our recent past but individual genomic admixture estimates are useful to test for association of admixture with phenotypes, as covariate in association studies to control for stratification and, in forensics, to estimate certain overt phenotypes from ancestry. We have developed a panel of 176 autosomal AIMs that can effectively distinguish I-BGA and admixture proportions from four continental ancestral populations: Europeans, West Africans, Indigenous Americans, and East Asians. We present allele frequencies for these AIMs in all four ancestral populations and use them to assess the global apportionment of I-BGA and admixture diversity among some extant populations. We observed patterns of apportionment similar to those described previously using sex and autosomal markers, such as European admixture for African Americans (14.3%) and Mexicans (43.2%), European (65.5%) and East Asian affiliation (27%) for South Asians, and low levels of African admixture (2.8,10.8%) mirroring the distribution of Y E3b haplogroups among various Eurasian populations. Using simulation studies and pedigree analysis we show that I-BGA estimates obtained using this panel and a four-population model has a high degree of precision (average root mean square error [RMSE]=0.026). Using ancestry,phenotype associations we demonstrate that a large and informative AIM panel such as this can help reduce false-positive and false-negative associations between phenotypes and admixture proportions, which may result when using a smaller panel of less informative AIMs. Hum Mutat 29(5), 648,658, 2008. © 2008 Wiley-Liss, Inc. [source] Virtual colonoscopy compared with conventional colonoscopy for stricturing postoperative recurrence in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 6 2003Dr. Livia Biancone Abstract Background The place of virtual colonoscopy (VC) in patients with Crohn's disease (CD) requiring endoscopic follow-up after surgery is unknown. The authors compared findings from VC versus conventional colonoscopy (CC) for assessing the postoperative recurrence of CD. Methods Sixteen patients with ileocolonic anastomosis for CD were prospectively enrolled from January 2001 to January 2002. Recurrence was assessed by CC according to Rutgeerts et al. VC was performed with a computed tomography scanner, with images examined by three radiologists who were unaware of the endoscopic findings. Results CC showed perianastomotic recurrence in 15 of 16 patients. Perianastomotic narrowing or stenosis was detected by VC in 11 of these 15 patients. There were 11 true positive, 1 true negative, 0 false-positive, and 4 false-negative findings (73% sensitivity, 100% specificity, 100% positive predictive value, 20% negative predictive value, 75% accuracy). Among the eight patients showing a rigid stenosis of the anastomosis not allowing passage of the colonoscope, VC detected narrowing or stenosis in seven patients. Conclusions The current findings suggest that although the widespread use of VC in CD is currently not indicated because of possible false-negative findings, this technique may represent an alternative to CC in noncompliant postsurgical patients with a rigid stenosis not allowing passage of the endoscope. [source] Multicenter Blinded Analysis of RT-PCR Detection Methods for Paramyxoviruses in Relation to Paget's Disease of Bone,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2007Stuart H Ralston MD Abstract Conflicting results have been reported on the detection of paramyxovirus transcripts in Paget's disease, and a possible explanation is differences in the sensitivity of RT-PCR methods for detecting virus. In a blinded study, we found no evidence to suggest that laboratories that failed to detect viral transcripts had less sensitive RT-PCR assays, and we did not detect measles or distemper transcripts in Paget's samples using the most sensitive assays evaluated. Introduction: There is conflicting evidence on the possible role of persistent paramyxovirus infection in Paget's disease of bone (PDB). Some workers have detected measles virus (MV) or canine distemper virus (CDV) transcripts in cells and tissues from patients with PDB, but others have failed to confirm this finding. A possible explanation might be differences in the sensitivity of RT-PCR methods for detecting virus. Here we performed a blinded comparison of the sensitivity of different RT-PCR,based techniques for MV and CDV detection in different laboratories and used the most sensitive assays to screen for evidence of viral transcripts in bone and blood samples derived from patients with PDB. Materials and Methods: Participating laboratories analyzed samples spiked with known amounts of MV and CDV transcripts and control samples that did not contain viral nucleic acids. All analyses were performed on a blinded basis. Results: The limit of detection for CDV was 1000 viral transcripts in three laboratories (Aberdeen, Belfast, and Liverpool) and 10,000 transcripts in another laboratory (Manchester). The limit of detection for MV was 16 transcripts in one laboratory (NIBSC), 1000 transcripts in two laboratories (Aberdeen and Belfast), and 10,000 transcripts in two laboratories (Liverpool and Manchester). An assay previously used by a U.S.-based group to detect MV transcripts in PDB had a sensitivity of 1000 transcripts. One laboratory (Manchester) detected CDV transcripts in a negative control and in two samples that had been spiked with MV. None of the other laboratories had false-positive results for MV or CDV, and no evidence of viral transcripts was found on analysis of 12 PDB samples using the most sensitive RT-PCR assays for MV and CDV. Conclusions: We found that RT-PCR assays used by different laboratories differed in their sensitivity to detect CDV and MV transcripts but found no evidence to suggest that laboratories that previously failed to detect viral transcripts had less sensitive RT-PCR assays than those that detected viral transcripts. False-positive results were observed with one laboratory, and we failed to detect paramyxovirus transcripts in PDB samples using the most sensitive assays evaluated. Our results show that failure of some laboratories to detect viral transcripts is unlikely to be caused by problems with assay sensitivity and highlight the fact that contamination can be an issue when searching for pathogens by sensitive RT-PCR,based techniques. [source] Evaluation of the Ortho-Clinical Diagnostics Vitros ECi Anti-HCV test: comparison with three other methodsJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2007Jeannette M. Watterson Abstract After observing a high incidence of low positive hepatitis C virus (HCV) antibody screens by the Ortho-Clinical Vitros ECi test (Orthoclinical Diagnostics, Raritan, NJ), we compared results against those obtained using another chemiluminescent analyzer, as well as two U.S. Food and Drug Administration (FDA)-approved confirmatory methodologies. To ascertain the true anti-HCV status of samples deemed low-positive by the Ortho-Clinical Vitros ECi test, we tested samples using the ADVIA Centaur HCV screen test (Siemens Medical Solutions Diagnostics), the Chiron recombinant immunoblot assay (RIBA) test (Chiron Corp., Emeryville, CA), and the Roche COBAS Amplicor HCV qualitative test (Roche Diagnostics, Indianapolis, IN) in a series of studies. Of 94 specimens positive by Vitros ECi, 19% were observed to be negative by Centaur. A separate study of 91 samples with signal-to-cutoff (s/co) values less than 8.0 showed that all but one was negative for HCV ribonucleic acid (RNA). In comparison with RIBA, 100% (77) samples positive by the Vitros ECi test with s/co values less than 12.0 were negative or indeterminate by RIBA. A final study comparing all four methods side-by-side showed 63% disagreement by Centaur for Vitros ECi low-positive samples, 75% disagreement by RIBA, and 97% disagreement by polymerase chain reaction (PCR). In conclusion, the Ortho-Clinical Vitros ECi Anti-HCV test yields a high rate of false-positive results in the low s/co range in our patient population. J. Clin. Lab. Anal. 21:162,166, 2007. © 2007 Wiley-Liss, Inc. [source] Sonographically guided fine needle aspiration of thyroid nodule: Discrepancies between cytologic and histopathologic findingsJOURNAL OF CLINICAL ULTRASOUND, Issue 1 2008Young Hen Lee MD Abstract Purpose To analyze the discrepancies between the cytologic results of sonographically (US)-guided fine needle aspiration (FNA) of thyroid nodules and final histopathologic results and to discuss the limitations of US-guided FNA. Materials and Methods The results of US-guided FNAs performed by a single experienced radiologist in 315 thyroid nodules in 292 patients (246 women, 46 men aged 12,79 years) were retrospectively correlated with their surgical pathologic results. The FNA results were classified as nondiagnostic, indeterminate, negative, or positive, whereas final pathologic diagnoses were classified as malignant or benign. Results The FNA results were nondiagnostic in 31 cases (9.8%), indeterminate in 97 cases (30.8%), and determinate in 187 cases (59.4%). Of the 187 conclusive cases, 169 (90.4%) were concordant with the final pathologic results, whereas 18 (9.6%) were discordant with 14 false-positive and 4 false-negative results. These discrepancies were caused by atypical nuclear features. Among the 97 indeterminate and 31 nondiagnostic cases, a malignancy was found in 14 (14.4%) and 8 (25.8%) cases, respectively. In addition, 10 papillary carcinomas, which were not visualized on sonograms, were detected incidentally in thyroidectomy specimens. Conclusion The diagnostic accuracy of US-guided FNA of thyroid nodule has limitations that should be minimized by careful interpretation of the cytologic findings and accurate sampling. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008 [source] Cystic appearance of cervical lymph nodes is characteristic of metastatic papillary thyroid carcinomaJOURNAL OF CLINICAL ULTRASOUND, Issue 1 2003Ada Kessler MD Abstract Purpose The usefulness of high-resolution sonography in diagnosing cervical lymph node metastases from papillary thyroid carcinoma was investigated. The accuracy of a particular sign, cystic change within a node, in establishing the diagnosis was assessed. Methods The sonographic findings in 63 patients with enlarged cervical lymph nodes were retrospectively reviewed. The patients had undergone high-resolution gray-scale and color Doppler sonography followed by ultrasound-guided fine-needle aspiration (FNA) in all patients and surgical excision in 27 patients. Results Abnormal sonographic features were present in the lymph nodes of all 63 patients. In 14 (70%) of 20 patients with papillary thyroid carcinoma, sonography depicted cystic changes. This pattern was not found in any of the other 43 patients, in whom FNA revealed either metastasis from another malignancy (22 patients) or benign reactive lymphadenopathy (21 patients). Among the 63 patients, there were 43 true-negative, 14 true-positive, 6 false-negative, and no false-positive results in the diagnosis of metastatic papillary thyroid carcinoma using the presence or absence of an intranodal cystic area on sonography. These results yielded a 70% sensitivity, 100% specificity, 100% positive predictive value, 88% negative predictive value, and 90% overall accuracy for this criterion. Conclusions Cystic changes within a cervical lymph node are highly suggestive of metastatic papillary thyroid carcinoma. © 2002 Wiley Periodicals, Inc. J Clin Ultrasound 31:21,25, 2003 [source] At what degree of belief in a research hypothesis is a trial in humans justified?JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 2 2002Benjamin Djulbegovic MD Abstract Rationale, aims and objectives,Randomized controlled trials (RCTs) have emerged as the most reliable method of assessing the effects of health care interventions in clinical medicine. However, RCTs should be undertaken only if there is substantial uncertainty about which of the trial treatments would benefit a patient most. The purpose of this study is to determine the degree of uncertainty in a research hypothesis before it can empirically be tested in an RCT. Methods,We integrated arguments from three independent lines of research , on ethics, principles of the design and conduct of clinical trials, and medical decision making , to develop a decision model to help solve the dilemma of under which circumstances innovative treatments should be tested in an RCT. Results,We showed that RCTs are the preferable option to resolve uncertainties about competing treatment alternatives whenever we desire reliable, undisputed, high-quality evidence with a low likelihood of false-positive or false-negative results. Conclusions When the expected benefit : risk ratio of a new treatment is small, an RCT is justified to resolve uncertainties over a wide range of prior belief (e.g. 10,90%) in the accuracy of the research hypothesis. Randomized controlled trials represent the best means for resolving uncertainties about health care interventions. [source] Multidetector CT pulmonary angiography features of pulmonary embolusJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 4 2008JK Hoang Summary Pulmonary embolism (PE) is a life-threatening condition. Multidetector CT pulmonary angiography is currently the imaging method of choice for the detection of PE. The aim of this pictorial essay is to review the appearances of PE on multidetector CT pulmonary angiography, including signs that differentiate acute and chronic PE and markers of severity. The features of a non-diagnostic study and pitfalls leading to a false-positive or false-negative study are presented. [source] Screening for Intracranial Stenosis With Transcranial Doppler: The Accuracy of Mean Flow Velocity ThresholdsJOURNAL OF NEUROIMAGING, Issue 1 2002Robert A. Felberg MD ABSTRACT Background. Patients with 50% intracranial arterial stenosis may require more intensive therapies for stroke prevention. Transcranial Doppler (TCD) is a convenient noninvasive screen for intracranial stenosis. The accuracy of different mean flow velocity (MFV) thresholds for determining the degree of stenosis remains uncertain. Methods. The authors prospectively compared the accuracy of TCD criteria and MFV thresholds to magnetic resonance, computed tomography, and digital subtraction angiography in patients with symptoms of recent or remote stroke or transient ischemic attack. Stenosis on angiography was measured as 0%, <50%, or ,50% diameter reduction. Results. Of 136 consecutive patients, 33 (24%) had distal internal carotid artery (ICA), middle cerebral artery (MCA), posterior cerebral artery, or basilar artery stenosis on angiography (14 patients [10%] were excluded due to incomplete TCD examinations, mainly from a lack of temporal windows). TCD showed 31 true-positive, 9 false-positive, 2 false-negative, and 94 true-negative studies. For all vessels, TCD had a sensitivity of 93.9% (confidence interval [CI] = 89%-98%), a specificity of 91.2% (CI = 87%-96%), a positive predictive value (PPV) of 77.5%, and a negative predictive value (NPV) of 97.9%. The trade-off in sensitivity and specificity for MCA MFV thresholds was as follows: MFV ,80 cm/s had a sensitivity of 100%, a specificity of 96.9% (CI = 94%-99%), a PPV of 84%, and an NPV of 100%. MFV,100 cm/s had a sensitivity of 100%, a specificity of 97.9% (CI = 96%-99%), a PPV of 88.8%, and an NPV of 94.9%. MFV,120 cm/s had a sensitivity of 68.7% (CI = 61%-78%), a specificity of 100%, a PPV of 100%, and an NPV of 94.9%. Reasons for false-positive findings include collateralization of flow in the presence of proximal ICA stenosis and prestenotic to stenotic MCA velocity ratios of 1:,2. Conclusion. TCD is both sensitive and specific in identifying ,50% intracranial arterial stenosis. A MFV threshold cutoff of 100 cm/s has an optimal sensitivity and specificity trade-off for ,50% MCA stenosis. To help avoid false-positive results, a prestenotic to stenotic MCA velocity ratio of 1:,2 should be used in addition to the MFV threshold. [source] A prospective comparative study between hysterosalpingography and hysteroscopy in the detection of intrauterine pathology in patients with infertilityJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2003Sangchai Preutthipan Abstract Aim: ,To investigate the accuracy of hysterosalpingography (HSG) in comparison to hysteroscopy in the detection of intrauterine pathology in patients with infertility, where hysteroscopy is the gold standard. Methods: ,A prospective, comparative study included 336 patients undergoing both HSG and diagnostic hysteroscopy. Main outcome measures were sensitivity, specificity, positive and negative predictive value, and accuracy rate of HSG. Results: ,Intrauterine abnormalities were shown on HSG in 286 patients and confirmed in 200 at hysteroscopy. Contrarily intrauterine lesions were detected by hysteroscopy in 4 out of 50 patients in whom HSG were normal. The most common intrauterine finding of 336 patients on hysteroscopy were intrauterine adhesions (IUA) (74), followed by endometrial polyps (56), and submucous myoma, 26 patients. Statistical analysis revealed that HSG in the detection of intrauterine pathology had a sensitivity of 98.0%, specificity of 34.9%, positive predictive value of 69.9%, negative predictive value of 92.0%, and accuracy rate of 73.2% with false-positive and false-negative rates of 30.1% and 8.0%, respectively. The common incorrect diagnoses of HSG were misdiagnosing a condition of cervical stenosis as severe IUA in 24 patients, endometrial polyps as submucous myoma in 22 out of 50 patients, and submucous myoma as endometrial polyps in 12 out of 72 patients. Conclusions: ,Hysterosalpingography is still a useful screening test for the evaluation of the uterine cavity. If a hysterogram demonstrates intrauterine abnormalities, hysteroscopy should be considered to make a definite diagnosis and treatment. Both procedures should be complementary to each other. [source] Insulin resistance is a major determinant of liver stiffness in nondiabetic patients with HCV genotype 1 chronic hepatitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009S. PETTA Summary Background, In patients with chronic hepatitis C (CHC), liver stiffness measurement (LSM) by transient elastography (TE), is closely related to the stage of fibrosis, but may be affected by necroinflammation. Other factors, such as insulin resistance (IR), might influence the performance of LSM. Aims, To evaluate in a cohort of nondiabetic patients with genotype 1 CHC, whether IR and other anthropometric, biochemical, metabolic and histological factors contribute to LSM and to identify the best cut-off values of LSM for predicting different stages of fibrosis. Methods, Nondiabetic patients with genotype 1 CHC (n = 156) were evaluated by liver biopsy (Metavir score), anthropometric, biochemical and metabolic features including IR. Furthermore, all subjects underwent LSM by TE. Results, Severe fibrosis (F3,F4) was associated with LSM (OR 1.291; 95%CI 1.106,1.508). LSM was also independently correlated with low platelets (P = 0.03), high ,GT (P < 0.001) and high HOMA (P = 0.004) levels. A stiffness value ,8 KPa was identified as the best cut-off for predicting severe fibrosis (AUC 0.870); yet this cut-off still failed to rule out F3,F4 fibrosis in 22.7% of patients (false-negative rate) or rule in F3,F4 in 19.6% (false-positive rate). Platelets <200 × 103/mmc and a HOMA of >2.7 were the major determinants of these diagnostic errors in predicting severe fibrosis. Conclusions, In nondiabetic patients with genotype 1 CHC, insulin resistance, ,GT and platelet levels contribute to LSM independently of liver fibrosis. The identification of these three factors contributes to a more correct interpretation of LSM. [source] In Vitro Cyclooxygenase-2 Protein Expression and Enzymatic Activity in Neoplastic CellsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2007David A. Heller Background: Cyclooxygenase-2 (COX-2) and its principle enzymatic metabolite, prostaglandin E2 (PGE2), are implicated in cancer progression. Based upon immunohistochemical (IHC) evidence that several tumor types in animals overexpress COX-2 protein, COX-2 inhibitors are used as anticancer agents in dogs and cats. Hypothesis: IHC is inaccurate for assessing tumor-associated COX-2 protein and enzymatic activity. Methods: Five mammalian cell lines were assessed for COX-2 protein expression by IHC and Western blot analysis (WB), and functional COX-2 activity was based upon PGE2 production. Results: Detection of COX-2 protein by IHC and WB were in agreement in 4 of 5 cell lines. In 1 cell line that lacked COX-2 gene transcription because of promoter hypermethylation (HCT-116), IHC produced false-positive staining for COX-2 protein expression. Functional COX-2 enzymatic activity was dissociated from relative IHC-based COX-2 protein expression in 2 cell lines (RPMI 2650 and SCCF1). The RPMI 2650 cell line demonstrated strong COX-2 protein expression but minimal PGE2 production. Conclusions and Clinical Importance: Western blot is more accurate than IHC for the detection of COX-2 protein in the cell lines studied. Furthermore, the semiquantitative identification of COX-2 protein by IHC or WB does not necessarily correlate with enzymatic activity. Based upon the potential inaccuracy of IHC and dissociation of COX-2 protein expression from enzymatic activity, the practice of instituting treatment of tumors with COX-2 inhibitors based solely on IHC results should be reconsidered. [source] Real-Time Polymerase Chain Reaction: A Novel Molecular Diagnostic Tool for Equine Infectious DiseasesJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2006N. Pusterla The focus of rapid diagnosis of infectious disease of horses in the last decade has shifted from the conventional laboratory techniques of antigen detection, microscopy, and culture to molecular diagnosis of infectious agents. Equine practitioners must be able to interpret the use, limitations, and results of molecular diagnostic techniques, as they are increasingly integrated into routine microbiology laboratory protocols. Polymerase chain reaction (PCR) is the best-known and most successfully implemented diagnostic molecular technology to date. It can detect slow-growing, difficult-to-cultivate, or uncultivatable microorganisms and can be used in situations in which clinical microbiology diagnostic procedures are inadequate, time-consuming, difficult, expensive, or hazardous to laboratory staff. Inherent technical limitations of PCR are present, but they are reduced in laboratories that use standardized protocols, conduct rigid validation protocols, and adhere to appropriate quality-control procedures. Improvements in PCR, especially probe-based real-time PCR, have broadened its diagnostic capabilities in clinical infectious diseases to complement and even surpass traditional methods in some situations. Furthermore, real-time PCR is capable of quantitation, allowing discrimination of clinically relevant infections characterized by pathogen replication and high pathogen loads from chronic latent infections. Automation of all components of PCR is now possible, which will decrease the risk of generating false-positive results due to contamination. The novel real-time PCR strategy and clinical applications in equine infectious diseases will be the subject of this review. [source] Evaluation of Chromocult® enterococci agar for the isolation and selective enumeration of Enterococcus spp. in broilersLETTERS IN APPLIED MICROBIOLOGY, Issue 2 2005J.M. Miranda Abstract Aims:, To investigate the productivity and specificity of a new chromogenic enterococci selective medium (Chromocult® enterococci agar) recently developed by Merck. Methods and Results:, The study was carried out comparing Chromocult® enterococci agar with MRS agar (Merck), a basal lactic acid bacteria medium in current use. A total of 216 faecal samples from poultry were collected and enterococci populations were counted. Likewise, 100 randomly selected strains were identified for each medium. The differences found between the two media were analysed and discussed. Conclusions:, A good sensitivity of 98% was obtained for Chromocult® agar and all false-positive isolates obtained were identified as Leuconostoc spp. However significant differences (P < 0·01) were obtained between the enterococci species isolation rates identified from these two media, suggesting the poor growth of some species in Chromocult® enterococci agar. Viable counts of Enterococcus spp. obtained with MRS agar were significantly higher than those obtained with Chromocult® enterococci agar. Significance and Impact of the Study:, The use of chromogenic media for microbiological analysis is increasing. Independent studies are important to evaluate newly developed chromogenic media. [source] Selective amplification of bacterial RNA: use of a DNA primer containing mismatched bases near its 3, terminus to reduce false-positive signalsLETTERS IN APPLIED MICROBIOLOGY, Issue 3 2000K. Koo A reverse transcription PCR (RT,PCR) method designed to reduce false-positive results due to the co-amplification of contaminating genomic DNA is reported. Feasibility of the method was evaluated using 16S rRNA sequences specific to Bacillus cereus. A DNA oligonucleotide primer, consisting of 22-bases containing three consecutive mismatched bases near its 3, terminus (primer B16RT), was used for reverse transcription and in subsequent cDNA amplification. Specific rRNA was reverse transcribed at low temperature (40 °C or 45 °C) in the presence of primer B16RT. As subsequent PCR using primer B16RT at high (62 °C) annealing temperatures is not nearly as efficient as amplification using the specific primer, amplification of genomic DNA was hindered relative to the amplification of cDNA. The method was readily adapted to the selective amplification of mRNA of the Listeria monocytogenes listeriolysin O (hly) gene. [source] | ||||||||||||||||||||||||||||||||||