scholarly journals False Positive Cardiotoxicity Events in Cancer-Related Clinical Trials: Risks Related to Imperfect Noninvasive Parameters

Chemotherapy ◽  
2018 ◽  
Vol 63 (6) ◽  
pp. 324-329 ◽  
Author(s):  
Michael S. Ewer ◽  
Jay Herson

Purpose: Cardiac ultrasound provides important structural and functional information that makes identification of cardiac abnormalities possible. Left ventricular ejection fraction (LVEF) provides the most commonly used parameter for recognition of treatment-related cardiac dysfunction. Random reading variance and physiologic factors influence LVEF and make the reported value imperfect. We attempt to quantitate the likelihood of false positive events by computer simulation. Methods: We simulated four visits on hypothetical trials. We assumed a baseline LVEF of 55% and normal distribution with regard to reading error and physiologic variation. 1,000 trials of sample size 1,500 were simulated. In a separate simulation, 1,000 patients entered with LVEFs of 45, 43, and 41% to estimate true positive incidence. Results: At each examination, less than 1.0% of false positives were noted. The cumulative false positive rate over four visits was 3.60%. True cardiotoxicity identification is satisfactory only when LVEF declines substantially. Conclusion: A 3.60% false positive rate in trials where the expected level of toxicity is low suggests that false positives are troubling and may exceed true positive results. Strategies to reduce the number of false positive results include making confirmatory studies mandatory. Evaluating increases along with decreases obtains some estimation of variance.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1900-1900
Author(s):  
Jennifer Rhamy ◽  
Mark Beltz ◽  
Karla John ◽  
David Feria ◽  
Dan Waxman ◽  
...  

Abstract Introduction: Donors of cord blood (CBD) are screened similarly to whole blood donors (WBD). It has been reported that CBD have a higher incidence of both true positive and false positive disease markers tested by EIA[1]. This abstract compares the rate of positive results for viral RNA (NAT) in CBD vs. WBD in a large cohort of donors. Methods: NAT was performed using the Chiron Procleix MPX or discriminatory assays. EIA testing was performed using Abbott bead methodology following manufacturer’s instructions. Confirmatory results for EIA were performed with Chiron RIBA. Results from 12/17/04 to 6/30/05 were collated. Results EIA HIV EIA HCV NAT HIV/HCV HIV EIA POS(%) HCV EIA POS (%) HIV NAT POS HCV NAT POS WBD 74299 74299 74299 75(0.10) 107(0.14) 1 (0) 31(0.04) CBD 11996 12001 12007 50(0.42) 46(0.38) 0 13 (0.11) A higher percentage of CBD were positive for HIV and HCV EIA as previously reported1. HIV NAT positive donors were 0.00% for both populations. The ratio of HCV EIA positive to HCV NAT positive donors was 28.97% for WBD and 28.26% in CBD. The ratio of CBD HCV EIA positives to WBD HCV EIA positives is 2.71 and the ratio of WBD HCV NAT positives to WBD HCV NAT positives is 2.75. The ratio of HIV CBD EIA positives to HIV WBD EIA positives is 4.10, which is significantly higher (p=<0.01). Conclusions Both CBD and WBD have a low rate (0%) of HIV NAT positive donors, but CBD have a 4x higher rate of HIV EIA. This suggests a 4x higher donor loss to false positive antibody results. The CBD donors have a 2.7x higher rate for both EIA and NAT positive results, showing a higher rate of viremic donors in CBD. The similar ratios for EIA positive to NAT positive donors in the two populations suggest that the false positive rate is not elevated in CBD versus WBD. The higher incidence of HCV infection in CBD could be geographic or ethnic in origin. More study is needed to determine the reasons and further predict donor loss. The HIV EIA results are not predictive of actual infection in this population. A more aggressive logarithm for reentry than used for WBD may be merited.


Electronics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1894
Author(s):  
Chun Guo ◽  
Zihua Song ◽  
Yuan Ping ◽  
Guowei Shen ◽  
Yuhei Cui ◽  
...  

Remote Access Trojan (RAT) is one of the most terrible security threats that organizations face today. At present, two major RAT detection methods are host-based and network-based detection methods. To complement one another’s strengths, this article proposes a phased RATs detection method by combining double-side features (PRATD). In PRATD, both host-side and network-side features are combined to build detection models, which is conducive to distinguishing the RATs from benign programs because that the RATs not only generate traffic on the network but also leave traces on the host at run time. Besides, PRATD trains two different detection models for the two runtime states of RATs for improving the True Positive Rate (TPR). The experiments on the network and host records collected from five kinds of benign programs and 20 famous RATs show that PRATD can effectively detect RATs, it can achieve a TPR as high as 93.609% with a False Positive Rate (FPR) as low as 0.407% for the known RATs, a TPR 81.928% and FPR 0.185% for the unknown RATs, which suggests it is a competitive candidate for RAT detection.


2014 ◽  
Vol 644-650 ◽  
pp. 3338-3341 ◽  
Author(s):  
Guang Feng Guo

During the 30-year development of the Intrusion Detection System, the problems such as the high false-positive rate have always plagued the users. Therefore, the ontology and context verification based intrusion detection model (OCVIDM) was put forward to connect the description of attack’s signatures and context effectively. The OCVIDM established the knowledge base of the intrusion detection ontology that was regarded as the center of efficient filtering platform of the false alerts to realize the automatic validation of the alarm and self-acting judgment of the real attacks, so as to achieve the goal of filtering the non-relevant positives alerts and reduce false positives.


2018 ◽  
Vol 5 (1) ◽  
pp. 171511 ◽  
Author(s):  
David Robert Grimes ◽  
Chris T. Bauch ◽  
John P. A. Ioannidis

Scientific publication is immensely important to the scientific endeavour. There is, however, concern that rewarding scientists chiefly on publication creates a perverse incentive, allowing careless and fraudulent conduct to thrive, compounded by the predisposition of top-tier journals towards novel, positive findings rather than investigations confirming null hypothesis. This potentially compounds a reproducibility crisis in several fields, and risks undermining science and public trust in scientific findings. To date, there has been comparatively little modelling on factors that influence science trustworthiness, despite the importance of quantifying the problem. We present a simple phenomenological model with cohorts of diligent, careless and unethical scientists, with funding allocated by published outputs. This analysis suggests that trustworthiness of published science in a given field is influenced by false positive rate, and pressures for positive results. We find decreasing available funding has negative consequences for resulting trustworthiness, and examine strategies to combat propagation of irreproducible science.


Author(s):  
Gregory A Kline ◽  
Jessica Boyd ◽  
Brenda Polzin ◽  
Adrian Harvey ◽  
Janice L Pasieka ◽  
...  

Abstract Context False positive results are common for pheochromocytoma/paraganglioma(PPGL) real-world screening. Objective Determine the correlation between screening urine and seated plasma metanephrines in outpatients where PPGL was absent, compared to meticulously prepared and supine-collected plasma metanephrines with age-adjusted references. Design Retrospective cohort study Setting Databases from a single-provider provincial laboratory(2012-2018), a validated PPGL registry and a manual chart review from a specialized endocrine testing unit. Patients PPGL registry data excluded known PPGL cases from the laboratory database. Outpatients having both urine and plasma metanephrines &lt;90 days apart. Methods The correlation between urine and seated plasma measures along with the total positivity rate. All cases of plasma metanephrines drawn in the endocrine unit were reviewed for test indication and test positivity rate. Results There were 810 non-PPGL pairs of urine and plasma metanephrines in the laboratory database; 46.1% of urine metanephrines were reported high. Of seated outpatient plasma metanephrines drawn a median of 5.9 days later, 19.2% were also high (r=0.33 and 0.50 for normetanephrine and metanephrine, respectively). In contrast, the meticulously prepared and supine collected patients(n=139, 51% prior high urine metanephrines) had &lt;3% rate of abnormal high results in patients without known PPGL/adrenal mass. Conclusions There was a poor-to-moderate correlation between urine and seated plasma metanephrines. Up to 20% of those with high urine measures also had high seated plasma metanephrines in the absence of PPGL. Properly prepared and collected supine plasma metanephrines had a false positive rate of &lt;3% in the absence of known PPGL/adrenal mass.


1979 ◽  
Vol 25 (12) ◽  
pp. 2034-2037 ◽  
Author(s):  
L B Sheiner ◽  
L A Wheeler ◽  
J K Moore

Abstract The percentage of mislabeled specimens detected (true-positive rate) and the percentage of correctly labeled specimens misidentified (false-positive rate) were computed for three previously proposed delta check methods and two linear discriminant functions. The true-positive rate was computed from a set of pairs of specimens, each having one member replaced by a member from another pair chosen at random. The relationship between true-positive and false-positive rates was similar among the delta check methods tested, indicating equal performance for all of them over the range of false-positive rate of interest. At a practical false-positive operating rate of about 5%, delta check methods detect only about 50% of mislabeled specimens; even if the actual mislabeling rate is moderate (e.g., 1%), only abot 10% of specimens flagged a by a delta check will actually have been mislabeled.


2020 ◽  
Vol 30 (12) ◽  
pp. 1851-1855
Author(s):  
Sruti Rao ◽  
M. B. Goens ◽  
Orrin B. Myers ◽  
Emilie A. Sebesta

AbstractAim:To determine the false-positive rate of pulse oximetry screening at moderate altitude, presumed to be elevated compared with sea level values and assess change in false-positive rate with time.Methods:We retrospectively analysed 3548 infants in the newborn nursery in Albuquerque, New Mexico, (elevation 5400 ft) from July 2012 to October 2013. Universal pulse oximetry screening guidelines were employed after 24 hours of life but before discharge. Newborn babies between 36 and 36 6/7 weeks of gestation, weighing >2 kg and babies >37 weeks weighing >1.7 kg were included in the study. Log-binomial regression was used to assess change in the probability of false positives over time.Results:Of the 3548 patients analysed, there was one true positive with a posteriorly-malaligned ventricular septal defect and an interrupted aortic arch. Of the 93 false positives, the mean pre- and post-ductal saturations were lower, 92 and 90%, respectively. The false-positive rate before April 2013 was 3.5% and after April 2013, decreased to 1.5%. There was a significant decrease in false-positive rate (p = 0.003, slope coefficient = −0.082, standard error of coefficient = 0.023) with the relative risk of a false positive decreasing at 0.92 (95% CI 0.88–0.97) per month.Conclusion:This is the first study in Albuquerque, New Mexico, reporting a high false-positive rate of 1.5% at moderate altitude at the end of the study in comparison to the false-positive rate of 0.035% at sea level. Implementation of the nationally recommended universal pulse oximetry screening was associated with a high false-positive rate in the initial period, thought to be from the combination of both learning curve and altitude. After the initial decline, it remained steadily elevated above sea level, indicating the dominant effect of moderate altitude.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ginette Lafit ◽  
Francis Tuerlinckx ◽  
Inez Myin-Germeys ◽  
Eva Ceulemans

AbstractGaussian Graphical Models (GGMs) are extensively used in many research areas, such as genomics, proteomics, neuroimaging, and psychology, to study the partial correlation structure of a set of variables. This structure is visualized by drawing an undirected network, in which the variables constitute the nodes and the partial correlations the edges. In many applications, it makes sense to impose sparsity (i.e., some of the partial correlations are forced to zero) as sparsity is theoretically meaningful and/or because it improves the predictive accuracy of the fitted model. However, as we will show by means of extensive simulations, state-of-the-art estimation approaches for imposing sparsity on GGMs, such as the Graphical lasso, ℓ1 regularized nodewise regression, and joint sparse regression, fall short because they often yield too many false positives (i.e., partial correlations that are not properly set to zero). In this paper we present a new estimation approach that allows to control the false positive rate better. Our approach consists of two steps: First, we estimate an undirected network using one of the three state-of-the-art estimation approaches. Second, we try to detect the false positives, by flagging the partial correlations that are smaller in absolute value than a given threshold, which is determined through cross-validation; the flagged correlations are set to zero. Applying this new approach to the same simulated data, shows that it indeed performs better. We also illustrate our approach by using it to estimate (1) a gene regulatory network for breast cancer data, (2) a symptom network of patients with a diagnosis within the nonaffective psychotic spectrum and (3) a symptom network of patients with PTSD.


2014 ◽  
Vol 77 (2) ◽  
pp. 308-313 ◽  
Author(s):  
M. C. BELTRÁN ◽  
M. BORRÀS ◽  
O. NAGEL ◽  
R. L. ALTHAUS ◽  
M. P. MOLINA

The suitability of different receptor-binding assays to detect antibiotics in raw goat's milk was investigated. Detection capability of most β-lactams and tetracyclines assessed applying the Betastar Combo, the SNAP Betalactam, the SNAP Tetracycline, and the Twinsensor tests was at or below maximum residue limits established by European legislation. Regarding test specificity, cross-reactions with antibiotics other than β-lactams and tetracyclines were not found, and no false-positive results were obtained for the Betastar Combo and the SNAP tests when bulk samples of goat's milk were analyzed. For the Twinsensor test, the false-positive rate was 1%. The performance of the Betastar Combo and the SNAP tests was practically unaffected by the milk quality parameters using individual samples of goat's milk collected at points throughout the entire lactation period (false-positive rate, ≤5%). However, a larger number of positive results were obtained by the Twinsensor test in this type of milk sample (&gt;10%), especially in the last weeks of lactation. Interferences related to the use of the preservative azidiol were not observed in any case. Neither were any significant differences found in relation to the interpretation method (visual versus instrumental) applied. In general, the response of the Betastar Combo, SNAP, and Twinsensor tests was optimal for the analysis of bulk caprine milk; thus, they may be used to monitor milk for the presence of β-lactam and tetracycline residues in quality control programs.


2007 ◽  
Vol 73 (19) ◽  
pp. 6296-6298 ◽  
Author(s):  
Hui-Zin Tu ◽  
Chiao-Shan Chen ◽  
Tsi-Shu Huang ◽  
Wen-Kuei Huang ◽  
Yao-shen Chen ◽  
...  

ABSTRACT A point-of-use 0.2-μm filter was evaluated for elimination of nontuberculosis mycobacteria in laboratory water to reduce false-positive acid-fast bacillus staining results. Use of the point-of-use filter can significantly reduce the false-positive rate to 1.2% compared to samples treated with tap water (10.7%) and deionized water (8.7%).


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