Development and validation of a real-world clinicogenomic database.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2514-2514 ◽  
Author(s):  
Gaurav Singal ◽  
Peter Grant Miller ◽  
Vineeta Agarwala ◽  
Jie He ◽  
Anala Gossai ◽  
...  
Keyword(s):  
Real World ◽  
Cancer Genomics ◽  
False Negative ◽  
Genomic Data ◽  
Female Gender ◽  
Driver Mutations ◽  
New Paradigm ◽  
Process Data ◽  
Genomic Databases ◽  
Negative Results

2514 Background: Genomic findings have diagnostic, prognostic, and predictive utility in clinical oncology. Population studies have been limited by reliance on trials, registries, or institutional chart review, which are costly and represent narrow populations. Integrating electronic health record (EHR) and genomic data collected as part of routine clinical practice may overcome these hurdles. Methods: Patients in the Flatiron Health Database with non-small cell lung cancer (NSCLC) who underwent comprehensive genomic profiling (CGP) by Foundation Medicine were included. EHR processing included structured data harmonization and abstraction of variables from unstructured documents. EHR and CGP data were de-identified and linked in a HIPAA-compliant process. Data included clinical characteristics, alterations across > 300 genes, tumor mutation burden (TMB), therapies and associated real-world responses, progression, and overall survival (OS). Results: The cohort (n = 1619) had expected clinical (mean age 66; 75% with smoking hx; 80% non-squamous) and genomic (18% EGFR; 4% ALK; 1% ROS1) properties of NSCLC. Presence of a driver mutation (EGFR, ALK, ROS1, MET, BRAF, RET, or ERBB2; n = 576) was associated with younger age, female gender, non-smoking, improved OS (35 vs 19 mo, LR p < 0.0001), and prolonged survival when treated with NCCN-recommended therapy (42 vs 28 mo, LR p = 0.001). CGP identified false negative results in up to 30% of single-biomarker tests for EGFR, ALK, and ROS1. CGP accuracy was supported by clinical outcomes. For example, 5 patients with prior negative ALK-fusion testing began ALK-directed therapy after positive CGP results. All 5 exhibited at least a partial response as recorded in the EHR by treating clinicians. Immunotherapy was used in 22% of patients (n = 353). TMB predicted response to nivolumab, including in PD-L1 negative populations. We recapitulated known associations with smoking, histology, and driver mutations. Conclusions: We present and validate a new paradigm for rapidly generating large, research-grade, longitudinal clinico-genomic databases by linking genomic data with EHR clinical annotation. This method offers a powerful tool for understanding cancer genomics and advancing precision medicine.

scholarly journals Effect of method of deduplication on estimation of differential gene expression using RNA-seq

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3091 ◽  
Author(s):  
Anna V. Klepikova ◽  
Artem S. Kasianov ◽  
Mikhail S. Chesnokov ◽  
Natalia L. Lazarevich ◽  
Aleksey A. Penin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Cancer Genomics ◽  
False Negative ◽  
Read Length ◽  
Rna Seq ◽  
Negative Results ◽  
Paired Samples ◽  
Highly Expressed Genes ◽  
Differential Gene

BackgroundRNA-seq is a useful tool for analysis of gene expression. However, its robustness is greatly affected by a number of artifacts. One of them is the presence of duplicated reads.ResultsTo infer the influence of different methods of removal of duplicated reads on estimation of gene expression in cancer genomics, we analyzed paired samples of hepatocellular carcinoma (HCC) and non-tumor liver tissue. Four protocols of data analysis were applied to each sample: processing without deduplication, deduplication using a method implemented in samtools, and deduplication based on one or two molecular indices (MI). We also analyzed the influence of sequencing layout (single read or paired end) and read length. We found that deduplication without MI greatly affects estimated expression values; this effect is the most pronounced for highly expressed genes.ConclusionThe use of unique molecular identifiers greatly improves accuracy of RNA-seq analysis, especially for highly expressed genes. We developed a set of scripts that enable handling of MI and their incorporation into RNA-seq analysis pipelines. Deduplication without MI affects results of differential gene expression analysis, producing a high proportion of false negative results. The absence of duplicate read removal is biased towards false positives. In those cases where using MI is not possible, we recommend using paired-end sequencing layout.

scholarly journals Burst Beliefs – Methodological Problems in the Balloon Analogue Risk Task and Implications for Its Use

10.36850/mr1 ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Kristel De Groot
Keyword(s):  
Risk Taking ◽  
Real World ◽  
False Negative ◽  
Risk Propensity ◽  
Balloon Analogue Risk Task ◽  
Negative Results ◽  
False Negative Results ◽  
Custom Made ◽  
Methodological Problems ◽  
Outcome Index

Studies in the field of psychology often employ (computerized) behavioral tasks, aimed at mimicking real-world situations that elicit certain actions in participants. Such tasks are for example used to study risk propensity, a trait-like tendency towards taking or avoiding risk. One of the most popular tasks for gauging risk propensity is the Balloon Analogue Risk Task (BART; Lejuez et al., 2002), which has been shown to relate well to self-reported risk-taking and to real-world risk behaviors. However, despite its popularity and qualities, the BART has several methodological shortcomings, most of which have been reported before, but none of which are widely known. In the present paper, four such problems are explained and elaborated on: a lack of clarity as to whether decisions are characterized by uncertainty or risk; censoring of observations; confounding of risk and expected value; and poor decomposability into adaptive and maladaptive risk behavior. Furthermore, for every problem, a range of possible solutions is discussed, which overall can be divided into three categories: using a different, more informative outcome index than the standard average pump score; modifying one or more task elements; or using a different task, either an alternative risk-taking task (sequential or otherwise), or a custom-made instrument. It is important to make use of these solutions, as applying the BART without accounting for its shortcomings may lead to interpretational problems, including false-positive and false-negative results. Depending on the research aims of a given study, certain shortcomings are more pressing than others, indicating the (type of) solutions most needed. By combining solutions and openly discussing shortcomings, researchers may be able to modify the BART in such a way that it can operationalize risk propensity without substantial methodological problems.

scholarly journals Real world assessment of SARS-CoV-2 nasopharyngeal swab testing in a high burden COVID-19 region

2021 ◽  
pp. 1-10
Author(s):  
Rohit B. Sangal ◽  
David R. Peaper ◽  
Craig Rothenberg ◽  
Hasan Fadlallah ◽  
Motunrayo Mobolaji-Lawal ◽  
...  
Keyword(s):  
Real World ◽  
False Negative ◽  
False Negative Rate ◽  
Healthcare Systems ◽  
Nasopharyngeal Swab ◽  
High Burden ◽  
Negative Results ◽  
Negative Rate ◽  
False Negative Results ◽  
True False

Abstract Concerns persist regarding possible false negative results that may compromise COVID-19 containment. While obtaining a true false negative rate is infeasible, using real world observation these data suggest a possible false negative rate to be approximately 2.3%. Use of a sensitive, amplified RNA platform should reassure healthcare systems.

Critical Evaluation of Impedance Phlebography for the Diagnosis of Deep Vein Thrombosis

1974 ◽  
Vol 31 (02) ◽  
pp. 273-278
Author(s):  
Kenneth K Wu ◽  
John C Hoak ◽  
Robert W Barnes ◽  
Stuart L Frankel
Keyword(s):  
Deep Vein Thrombosis ◽  
False Positive ◽  
False Negative ◽  
Critical Evaluation ◽  
Original Method ◽  
Vein Thrombosis ◽  
Negative Results ◽  
False Negative Results ◽  
Deep Vein ◽  
Positive Results

SummaryIn order to evaluate its daily variability and reliability, impedance phlebography was performed daily or on alternate days on 61 patients with deep vein thrombosis, of whom 47 also had 125I-fibrinogen uptake tests and 22 had radiographic venography. The results showed that impedance phlebography was highly variable and poorly reliable. False positive results were noted in 8 limbs (18%) and false negative results in 3 limbs (7%). Despite its being simple, rapid and noninvasive, its clinical usefulness is doubtful when performed according to the original method.

The role of serum periostin in the diagnosis of asthma: A meta-analysis

2020 ◽  
Vol 41 (4) ◽  
pp. 240-247
Author(s):  
Lei Yang ◽  
Qingtao Zhao ◽  
Shuyu Wang
Keyword(s):  
Diagnostic Accuracy ◽  
Meta Analysis ◽  
Characteristic Curve ◽  
False Negative ◽  
Summary Receiver Operating Characteristic ◽  
True Negative ◽  
Negative Results ◽  
Noninvasive Biomarker ◽  
Sensitivity Specificity ◽  
Serum Periostin

Background: Serum periostin has been proposed as a noninvasive biomarker for asthma diagnosis and management. However, its accuracy for the diagnosis of asthma in different populations is not completely clear. Methods: This meta-analysis aimed to evaluate the diagnostic accuracy of periostin level in the clinical determination of asthma. Several medical literature data bases were searched for relevant studies through December 1, 2019. The numbers of patients with true-positive, false-positive, false-negative, and true-negative results for the periostin level were extracted from each individual study. We assessed the risk of bias by using Quality Assessment of Diagnostic Accuracy Studies 2. We used the meta-analysis to produce summary estimates of accuracy. Results: In total, nine studies with 1757 subjects met the inclusion criteria. The pooled estimates of sensitivity, specificity, and diagnostic odds ratios for the detection of asthma were 0.58 (95% confidence interval [CI], 0.38‐0.76), 0.86 (95% CI, 0.74‐0.93), and 8.28 (95% CI, 3.67‐18.68), respectively. The area under the summary receiver operating characteristic curve was 0.82 (95% CI, 0.79‐0.85). And significant publication bias was found in this meta‐analysis (p = 0.39). Conclusion: Serum periostin may be used for the diagnosis of asthma, with moderate diagnostic accuracy.

Scoring System for the Diagnosis of COVID-19

2020 ◽  
Vol 13 (1) ◽  
pp. 413-414 ◽  
Author(s):  
Mohamed Farouk Allam
Keyword(s):  
Scoring System ◽  
Clinical Symptoms ◽  
False Negative ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Negative Results ◽  
False Negative Results ◽  
Symptoms And Signs

Due to the international spread of COVID-19, the difficulty of collecting nasopharyngeal swab specimen from all suspected patients, the costs of RT-PCR and CT, and the false negative results of RT-PCR assay in 41% of COVID-19 patients, a scoring system is needed to classify the suspected patients in order to determine the need for follow-up, home isolation, quarantine or the conduction of further investigations. A scoring system is proposed as a diagnostic tool for suspected patients. It includes Epidemiological Evidence of Exposure, Clinical Symptoms and Signs, and Investigations (if available). This scoring system is simple, could be calculated in a few minutes, and incorporates the main possible data/findings of any patient.

Detection of Streptococcus pneumoniae in Sputum Samples by Real- Time PCR.

2020 ◽  
Vol 18 ◽  
Author(s):  
Pegah Shakib ◽  
Mohammad Reza Zolfaghari
Keyword(s):  
Streptococcus Pneumoniae ◽  
Real Time ◽  
Real Time Pcr ◽  
False Negative ◽  
Cross Sectional Study ◽  
Laboratory Culture ◽  
Cross Sectional ◽  
Negative Results ◽  
False Negative Results ◽  
Pcr Method

Background: Conventional laboratory culture-based methods for diagnosis of Streptococcus pneumoniae are time-consuming and yield false negative results. Molecular methods including real-time (RT)-PCR rapid methods and conventional PCR due to higher sensitivity and accuracy have been replaced instead traditional culture assay. The aim of the current study was to evaluate lytA gene for detection of Streptococcus pneumoniae in the cerebrospinal fluid of human patients with meningitis using real-time PCR assay. Material and Methods: In this cross-sectional study, a total of 30 clinical specimens were collected from patients in a period from September to December 2018. In order to evaluate the presence of lytA gene, conventional and real-time PCR methods were used without culture. Results: From 30 sputum samples five (16.66%) isolates were identified as S. pneumoniae by lytA PCR and sequencing. Discussion: In this research, an accurate and rapid real-time PCR method was used, which is based on lytA gene for diagnosis of bacteria so that it can be diagnosed. Based on the sequencing results, the sensitivity for detection of lytA gene was 100% (5/5).

COVID-19: how nuclear medicine can provide a differential diagnosis in very dubious case

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Maria Silvia De Feo ◽  
Viviana Frantellizzi ◽  
Giuseppe De Vincentis
Keyword(s):  
Infectious Disease ◽  
Differential Diagnosis ◽  
Ct Scan ◽  
Imaging Technique ◽  
False Negative ◽  
Clinical Signs ◽  
Negative Results ◽  
Infectious Disease Department ◽  
False Negative Results ◽  
99Mtc Hmpao

Background: We present the case of a 55-year-old woman, admitted to the Infectious Disease Department of Policlinico Umberto I, Rome, in mid-March 2020, with suspicion of COVID-19 infection. Objective: The rRT-PCR was negative and the following CT scan, performed to exclude false-negative results and help diagnosis, was inconclusive. Methods: It was decided to submit the patient to 99mTc-HMPAO-labelled leukocyte scan. Results: This exam led to the diagnosis of infective endocarditis. Conclusion: In the present pandemic scenario, 99mTc-HMPAO-labelled leukocyte scan represents a reliable imaging technique for differential diagnosis with COVID-19 in patients with confusing clinical signs, possible false-negative rRT-PCR results and inconclusive CT scan.

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