scholarly journals Understanding False Negative in Prenatal Testing

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 888
Author(s):  
Mark I. Evans ◽  
Ming Chen ◽  
David W. Britt
Keyword(s):  
Prenatal Screening ◽  
False Negative ◽  
Prenatal Testing ◽  
Quality Service ◽  
False Negatives ◽  
Affected Child ◽  
Medical Tests ◽  
Trade Offs ◽  
Shed Light ◽  
Screening And Diagnosis

A false negative can happen in many kinds of medical tests, regardless of whether they are screening or diagnostic in nature. However, it inevitably poses serious concerns especially in a prenatal setting because its sequelae can mark the birth of an affected child beyond expectation. False negatives are not a new thing because of emerging new tests in the field of reproductive, especially prenatal, genetics but has occurred throughout the evolution of prenatal screening and diagnosis programs. In this paper we aim to discuss the basic differences between screening and diagnosis, the trade-offs and the choices, and also shed light on the crucial points clinicians need to know and be aware of so that a quality service can be provided in a coherent and sensible way to patients so that vital issues related to a false negative result can be appropriately comprehended by all parties.

Noninvasive prenatal testing for fetal trisomy 9 mosaicism by maternal plasma DNA sequencing

2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Luming Sun ◽  
Lei Zhang ◽  
Jia Zhou ◽  
Xiaonan Yang ◽  
Tao Duan ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Trisomy 21 ◽  
Prenatal Screening ◽  
Detection Efficiency ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Plasma Dna ◽  
Noninvasive Prenatal Testing ◽  
Trisomy 9 ◽  
Screening And Diagnosis

AbstractMaternal plasma DNA sequencing based noninvasive prenatal testing (NIPT) has been proven to be highly accurate in the detection of trisomy 21, 18, 13, X and Y, however, few reports have been made on its detection efficiency of rare complex aneuploidies. Here, we report a case of fetal trisomy 9 mosaicism identified by using NIPT, which may provide useful information for the further integration of NIPT into prenatal screening and diagnosis practice.

Clinically Meaningful Change

Methodology ◽  
2019 ◽  
Vol 15 (3) ◽  
pp. 97-105
Author(s):  
Rodrigo Ferrer ◽  
Antonio Pardo
Keyword(s):  
Effect Size ◽  
False Negative ◽  
False Negative Rate ◽  
Point Of View ◽  
Skewed Distribution ◽  
Effect Sizes ◽  
False Negatives ◽  
Large Size ◽  
Before And After ◽  
Post Test

Abstract. In a recent paper, Ferrer and Pardo (2014) tested several distribution-based methods designed to assess when test scores obtained before and after an intervention reflect a statistically reliable change. However, we still do not know how these methods perform from the point of view of false negatives. For this purpose, we have simulated change scenarios (different effect sizes in a pre-post-test design) with distributions of different shapes and with different sample sizes. For each simulated scenario, we generated 1,000 samples. In each sample, we recorded the false-negative rate of the five distribution-based methods with the best performance from the point of view of the false positives. Our results have revealed unacceptable rates of false negatives even with effects of very large size, starting from 31.8% in an optimistic scenario (effect size of 2.0 and a normal distribution) to 99.9% in the worst scenario (effect size of 0.2 and a highly skewed distribution). Therefore, our results suggest that the widely used distribution-based methods must be applied with caution in a clinical context, because they need huge effect sizes to detect a true change. However, we made some considerations regarding the effect size and the cut-off points commonly used which allow us to be more precise in our estimates.

scholarly journals No evidence of false-negative Plasmodium falciparum rapid diagnostic results in Monrovia, Liberia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mandella King ◽  
Alexander E. George ◽  
Pau Cisteró ◽  
Christine K. Tarr-Attia ◽  
Beatriz Arregui ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
False Negative ◽  
Malaria Diagnosis ◽  
Rapid Diagnostic Tests ◽  
Molecular Testing ◽  
False Negatives ◽  
Gene Deletions ◽  
History Of ◽  
Catholic Hospital ◽  
Or History

Abstract Background Malaria diagnosis in many malaria-endemic countries relies mainly on the use of rapid diagnostic tests (RDTs). The majority of commercial RDTs used in Africa detect the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). pfhrp2/3 gene deletions can therefore lead to false-negative RDT results. This study aimed to evaluate the frequency of PCR-confirmed, false-negative P. falciparum RDT results in Monrovia, Liberia. Methods PfHRP2-based RDT (Paracheck Pf®) and microscopy results from 1038 individuals with fever or history of fever (n = 951) and pregnant women at first antenatal care (ANC) visit (n = 87) enrolled in the Saint Joseph’s Catholic Hospital (Monrovia) from March to July 2019 were used to assess the frequency of false-negative RDT results. True–false negatives were confirmed by detecting the presence of P. falciparum DNA by quantitative PCR in samples from individuals with discrepant RDT and microscopy results. Samples that were positive by 18S rRNA qPCR but negative by PfHRP2-RDT were subjected to multiplex qPCR assay for detection of pfhrp2 and pfhrp3. Results One-hundred and eighty-six (19.6%) and 200 (21.0%) of the 951 febrile participants had a P. falciparum-positive result by RDT and microscopy, respectively. Positivity rate increased with age and the reporting of joint pain, chills and shivers, vomiting and weakness, and decreased with the presence of coughs and nausea. The positivity rate at first ANC visit was 5.7% (n = 5) and 8% (n = 7) by RDT and microscopy, respectively. Out of 207 Plasmodium infections detected by microscopy, 22 (11%) were negative by RDT. qPCR confirmed absence of P. falciparum DNA in the 16 RDT-negative but microscopy-positive samples which were available for molecular testing. Among the 14 samples that were positive by qPCR but negative by RDT and microscopy, 3 only amplified pfldh, and among these 3 all were positive for pfhrp2 and pfhrp3. Conclusion There is no qPCR-confirmed evidence of false-negative RDT results due to pfhrp2/pfhrp3 deletions in this study conducted in Monrovia (Liberia). This indicates that these deletions are not expected to affect the performance of PfHRP2-based RDTs for the diagnosis of malaria in Liberia. Nevertheless, active surveillance for the emergence of PfHRP2 deletions is required.

scholarly journals Testing Segmentation Popular Loss and Variations in Three Multiclass Medical Imaging Problems

2021 ◽  
Vol 7 (2) ◽  
pp. 16
Author(s):  
Pedro Furtado
Keyword(s):  
False Negative ◽  
Magnetic Resonance Images ◽  
Medical Image Segmentation ◽  
Cross Entropy ◽  
Loss Functions ◽  
Optic Disk ◽  
False Negatives ◽  
Convolutional Network ◽  
Percentage Points ◽  
Class Background

Image structures are segmented automatically using deep learning (DL) for analysis and processing. The three most popular base loss functions are cross entropy (crossE), intersect-over-the-union (IoU), and dice. Which should be used, is it useful to consider simple variations, such as modifying formula coefficients? How do characteristics of different image structures influence scores? Taking three different medical image segmentation problems (segmentation of organs in magnetic resonance images (MRI), liver in computer tomography images (CT) and diabetic retinopathy lesions in eye fundus images (EFI)), we quantify loss functions and variations, as well as segmentation scores of different targets. We first describe the limitations of metrics, since loss is a metric, then we describe and test alternatives. Experimentally, we observed that DeeplabV3 outperforms UNet and fully convolutional network (FCN) in all datasets. Dice scored 1 to 6 percentage points (pp) higher than cross entropy over all datasets, IoU improved 0 to 3 pp. Varying formula coefficients improved scores, but the best choices depend on the dataset: compared to crossE, different false positive vs. false negative weights improved MRI by 12 pp, and assigning zero weight to background improved EFI by 6 pp. Multiclass segmentation scored higher than n-uniclass segmentation in MRI by 8 pp. EFI lesions score low compared to more constant structures (e.g., optic disk or even organs), but loss modifications improve those scores significantly 6 to 9 pp. Our conclusions are that dice is best, it is worth assigning 0 weight to class background and to test different weights on false positives and false negatives.

scholarly journals Performance of Cell-Free DNA Screening for Fetal Common Aneuploidies and Sex Chromosomal Abnormalities: A Prospective Study from a Less Developed Autonomous Region in Mainland China

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 478
Author(s):  
Yunli Lai ◽  
Xiaofan Zhu ◽  
Sheng He ◽  
Zirui Dong ◽  
Yanqing Tang ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
False Negative ◽  
Prenatal Testing ◽  
Read Depth ◽  
Trisomy 13 ◽  
Prognostic Information ◽  
Aneuploidy Screening ◽  
Predictive Values ◽  
Risk Result

To evaluate the performance of noninvasive prenatal screening (NIPS) in the detection of common aneuploidies in a population-based study, a total of 86,262 single pregnancies referred for NIPS were prospectively recruited. Among 86,193 pregnancies with reportable results, follow-up was successfully conducted in 1160 fetuses reported with a high-risk result by NIPS and 82,511 cases (95.7%) with a low-risk result. The screen-positive rate (SPR) of common aneuploidies and sex chromosome abnormalities (SCAs) provided by NIPS were 0.7% (586/83,671) and 0.6% (505/83,671), respectively. The positive predictive values (PPVs) for Trisomy 21, Trisomy 18, Trisomy 13 and SCAs were calculated as 89.7%, 84.0%, 52.6% and 38.0%, respectively. In addition, less rare chromosomal abnormalities, including copy number variants (CNVs), were detected, compared with those reported by NIPS with higher read-depth. Among these rare abnormalities, only 23.2% (13/56) were confirmed by prenatal diagnosis. In total, four common trisomy cases were found to be false negative, resulting in a rate of 0.48/10,000 (4/83,671). In summary, this study conducted in an underdeveloped region with limited support for the new technology development and lack of cost-effective prenatal testing demonstrates the importance of implementing routine aneuploidy screening in the public sector for providing early detection and precise prognostic information.

scholarly journals Characteristics of patients who had a stroke not initially identified during emergency prehospital assessment: a systematic review

2021 ◽  
pp. emermed-2020-209607
Author(s):  
Stephanie P Jones ◽  
Janet E Bray ◽  
Josephine ME Gibson ◽  
Graham McClelland ◽  
Colette Miller ◽  
...  
Keyword(s):  
Systematic Review ◽  
Diagnostic Accuracy ◽  
False Negative ◽  
Visual Disturbance ◽  
Screening Tools ◽  
False Negatives ◽  
Presenting Symptoms ◽  
Ischaemic Attack ◽  
Stroke Type ◽  
Key Terms

BackgroundAround 25% of patients who had a stroke do not present with typical ‘face, arm, speech’ symptoms at onset, and are challenging for emergency medical services (EMS) to identify. The aim of this systematic review was to identify the characteristics of acute stroke presentations associated with inaccurate EMS identification (false negatives).MethodWe performed a systematic search of MEDLINE, EMBASE, CINAHL and PubMed from 1995 to August 2020 using key terms: stroke, EMS, paramedics, identification and assessment. Studies included: patients who had a stroke or patient records; ≥18 years; any stroke type; prehospital assessment undertaken by health professionals including paramedics or technicians; data reported on prehospital diagnostic accuracy and/or presenting symptoms. Data were extracted and study quality assessed by two researchers using the Quality Assessment of Diagnostic Accuracy Studies V.2 tool.ResultsOf 845 studies initially identified, 21 observational studies met the inclusion criteria. Of the 6934 stroke and Transient Ischaemic Attack patients included, there were 1774 (26%) false negative patients (range from 4 (2%) to 247 (52%)). Commonly documented symptoms in false negative cases were speech problems (n=107; 13%–28%), nausea/vomiting (n=94; 8%–38%), dizziness (n=86; 23%–27%), changes in mental status (n=51; 8%–25%) and visual disturbance/impairment (n=43; 13%–28%).ConclusionSpeech problems and posterior circulation symptoms were the most commonly documented symptoms among stroke presentations that were not correctly identified by EMS (false negatives). However, the addition of further symptoms to stroke screening tools requires valuation of subsequent sensitivity and specificity, training needs and possible overuse of high priority resources.

scholarly journals Validity of negative bone biopsy in suspicious bone lesions

2021 ◽  
Vol 10 (7) ◽  
pp. 205846012110306
Author(s):  
Mine B Lange ◽  
Lars J Petersen ◽  
Michael B Nielsen ◽  
Helle D Zacho
Keyword(s):  
Bone Biopsy ◽  
False Negative ◽  
Exclusion Criterion ◽  
Bone Lesions ◽  
False Negatives ◽  
Patient Morbidity ◽  
Bone Biopsies ◽  
Initial Biopsy ◽  
Valid Criterion

Background The presence of malignant cells in bone biopsies is considered gold standard to verify occurrence of cancer, whereas a negative bone biopsy can represent a false negative, with a risk of increasing patient morbidity and mortality and creating misleading conclusions in cancer research. However, a paucity of literature documents the validity of negative bone biopsy as an exclusion criterion for the presence of skeletal malignancies. Purpose To investigate the validity of a negative bone biopsy in bone lesions suspicious of malignancy. Material and Method A retrospective cohort of 215 consecutive targeted non-malignant skeletal biopsies from 207 patients (43% women, 57% men, median age 64, and range 94) representing suspicious focal bone lesions, collected from January 1, 2011, to July 31, 2013, was followed over a 2-year period to examine any additional biopsy, imaging, and clinical follow-up information to categorize the original biopsy as truly benign, malignant, or equivocal. Standard deviations and 95% confidence intervals were calculated. Results 210 of 215 biopsies (98%; 95% CI 0.94–0.99) showed to be truly benign 2 years after initial biopsy. Two biopsies were false negatives (1%; 95% CI 0.001–0.03), and three were equivocal (lack of imaging description). Conclusion Our study documents negative bone biopsy as a valid criterion for the absence of bone metastasis. Since only 28% had a confirmed diagnosis of prior cancer and not all patients received adequately sensitive imaging, our results might not be applicable to all cancer patients with suspicious bone lesions.

scholarly journals Non-Invasive Prenatal Testing: Current Perspectives and Future Challenges

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 15
Author(s):  
Luigi Carbone ◽  
Federica Cariati ◽  
Laura Sarno ◽  
Alessandro Conforti ◽  
Francesca Bagnulo ◽  
...  
Keyword(s):  
Prenatal Screening ◽  
Prenatal Testing ◽  
Non Invasive ◽  
Fetal Dna ◽  
Cell Free Fetal Dna ◽  
Common Causes ◽  
Future Challenges ◽  
Neurodevelopmental Impairment ◽  
Fetal Aneuploidies ◽  
Made In

Fetal aneuploidies are among the most common causes of miscarriages, perinatal mortality and neurodevelopmental impairment. During the last 70 years, many efforts have been made in order to improve prenatal diagnosis and prenatal screening of these conditions. Recently, the use of cell-free fetal DNA (cff-DNA) testing has been increasingly used in different countries, representing an opportunity for non-invasive prenatal screening of pregnant women. The aim of this narrative review is to describe the state of the art and the main strengths and limitations of this test for prenatal screening of fetal aneuploidies.

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