Increase In False-negative Rate Research Articles

Reinterpretation of the results of randomized clinical trials.

Randomized clinical trials (RCTs) shape our clinical practice. Several studies report a mediocre replicability rate of the studied RCTs. Many researchers believe that the relatively low replication rate of RCTs is attributed to the high p value significance threshold. To solve this problem, some researchers proposed using a lower threshold, which is inevitably associated with a decrease in the study power. The results of 22 500 RCTs retrieved from the Cochrane Database of Systematic Reviews (CDSR) were reinterpreted using 2 fixed p significance threshold (0.05 and 0.005), and a recently proposed flexible threshold that minimizes the weighted sum of errors in statistical inference. With p < 0.05 criterion, 28.5% of RCTs were significant; p < 0.005, 14.2%; and p < flexible threshold, 9.9% (2/3 of significant RCTs based on p < 0.05 criterion, were found not significant). Lowering the p cut-off, although decreases the false-positive rate, is not generally associated with a lower weighted sum of errors; the false-negative rate increases (the study power decreases); important treatments may be left undiscovered. Accurate calculation of the optimal p value thresholds needs knowledge of the variance in each study arm, a posteriori. Lowering the p value threshold, as it is proposed by some researchers, is not reasonable as it might be associated with an increase in false-negative rate. Using a flexible p significance threshold approach, although results in a minimum error in statistical inference, might not be good enough too because only a rough estimation may be calculated a priori; the data necessary for the precise computation of the most appropriate p significance threshold are only available a posteriori. Frequentist statistical framework has an inherent conflict. Alternative methods, say Bayesian methods, although not perfect, would be more appropriate for the data analysis of RCTs.

Cyto-histo correlation and false-negative urine: Before and after the Paris system for reporting urinary cytology.

The impact of implementing the Paris system (TPS) on the rate of discrepant cases in the negative for high-grade urothelial carcinoma (NHGUC) category that had a subsequent diagnosis of high-grade urothelial carcinoma (HGUC) on histology is not well studied. We adopted TPS in May 2019. We searched discrepant cases with negative urine cytology 2017-2019 in our cyto-histo correlation database. The urine cytology and follow-up biopsy/resection were reviewed by a cytopathologist who also did Genitourinary (GU) Pathology subspecialty sign-out. Voided urine and instrumented urine were included in this study. There were total of 70 discrepant cases with negative cytology interpretation but HGUC on the subsequent biopsy or resected specimen. Following the TPS criteria, the rate of discrepant negative cytology cases increased from 6 cases between January 2017 and May 2019 to 64 cases after May 2019 when we adopted TPS. There were 2 discrepant negative cases in 2017, 3 cases in 2018, and 65 cases in 2019. Out of 65 cases in 2019, 64 cases were identified after May 2019. Additional 55 urine cytology slides were reviewed according to the TPS criteria, of which, the diagnoses remained unchanged in 45 (82%) cases and 10 (19%) cases were reassigned to either atypical or suspicious categories. The discrepancy was noted more on the instrumented urine and the upper tract urine. However, the false-negative rate rose faster in voided urine and lower tract urine. The risk of HGUC with the category of NHGUC was 0.03% in 2017, 0.05% in 2018, and 1.06% in 2019 at our institution. The increase in false-negative rate could not be attributed to a single cytopathologist. After adopting TPS for reporting urine cytology, there was an increase in HGUC from negative urine cytology which was subsequently confirmed on histology as cases of HGUC. The quality control of negative urines could be important monitoring the process when implementing TPS.

Increasing False Negative RT-PCR Test in COVID-19 Patients Admitted at Tertiary Care Hospital: A Retrospective Cross-Sectional Study

Background: COVID-19 Pandemic has caused a lot of havoc for the human race, as the urgent need to detect the virus early and fight back stronger, scientists came up with the test RT-PCR, which later on was declared as the gold standard. But lately, an exponential increase in false-negative rates was observed, which calls for an accuracy check of the test and the statistical analysis of the reasons leading false-positive results. With the advent of the COVID-19 Pandemic, RT-PCR testing has become the gold standard for laboratory diagnosis of SARS-CoV-2 infection. But the second wave of COVID-19 in India has reported a high number of false-negative RT-PCR results. This calls for the need to measure the accuracy of the test in diagnosing infection, especially considering rise in variant strains each with its own virulence and infectivity. Imaging methods like HRCT and biochemical tests such as CRP, D-Dimer are being used increasingly by doctors to support the serological diagnostic method of Covid and draft further treatment protocols&#x0D; Objectives: To measure the false negative rates of RT-PCR in COVID-19 Patients. To find the epidemiology of the root cause.&#x0D; Methodology: For this Retrospective Cross-sectional study, sample size of 1998 with prevalence of 7894/million population and confidence interval of 95% we would be analysing patients of Datta Meghe Institute of Medical Sciences TCH admitted in the months of April to June 2021 with suspected COVID-19 Infection.&#x0D; Results: Increasing cases of false negative RT-PCR reports would be found.&#x0D; Conclusion: There is an urgent need for the reality check on efficacy of RT-PCR Test Reports.

Consecutive Case Series of Melanoma Sentinel Node Biopsy for Lymphoseek Compared to Sulfur Colloids

BackgroundSentinel lymph node biopsy (SLNB) is an important adjunct in the staging of patients with melanoma. Preoperative lymphoscintigraphy with radiolabeled isotopes is essential to localize sentinel nodes for removal. Our study compared the effectiveness of Lymphoseek to standard sulfur colloids in patients with melanoma undergoing SLNB. MethodsWe queried our IRB-approved melanoma database to identify 370 consecutive patients who underwent SLNB from 2012 to 2016 with at least 1 y of follow-up. There were 185 patients in each group. Data points included characteristics of the primary melanoma lymphoscintigraphy and SLNB. Student's t-test and chi-square were used to analyze the data with a P value of <0.05 being considered significant. ResultsPatients were equally matched in regard to age, sex, and primary characteristics of their melanoma. In comparison to sulfur colloid, Lymphoseek required lower radiation dosages (P < 0.001), shorter mapping times (P = 0.008), and decreased number of sentinel nodes removed (P = 0.03). There was no difference in the number of patients with positive nodes (P = 0.5). In addition, there were no statistical differences between the two radioactive tracers in regard to the number of patients with false-negative SLNB. ConclusionLymphoseek has the potential to decrease radioactivity and mapping time in patients who need SLNB. With a decrease in the number of nodes removed without loss of sensitivity, there is a potential to avoid unnecessary node removal and thus complications such as lymphedema. Longer follow-up will help to determine if there is any increase in false-negative rates despite fewer nodes removed.

Integrative analysis with ChIP-seq advances the limits of transcript quantification from RNA-seq.

RNA-seq is currently the technology of choice for global measurement of transcript abundances in cells. Despite its successes, isoform-level quantification remains difficult because short RNA-seq reads are often compatible with multiple alternatively spliced isoforms. Existing methods rely heavily on uniquely mapping reads, which are not available for numerous isoforms that lack regions of unique sequence. To improve quantification accuracy in such difficult cases, we developed a novel computational method, prior-enhanced RSEM (pRSEM), which uses a complementary data type in addition to RNA-seq data. We found that ChIP-seq data of RNA polymerase II and histone modifications were particularly informative in this approach. In qRT-PCR validations, pRSEM was shown to be superior than competing methods in estimating relative isoform abundances within or across conditions. Data-driven simulations suggested that pRSEM has a greatly decreased false-positive rate at the expense of a small increase in false-negative rate. In aggregate, our study demonstrates that pRSEM transforms existing capacity to precisely estimate transcript abundances, especially at the isoform level.

Empirical extensions of the lasso penalty to reduce the false discovery rate in high-dimensional Cox regression models.

Correct selection of prognostic biomarkers among multiple candidates is becoming increasingly challenging as the dimensionality of biological data becomes higher. Therefore, minimizing the false discovery rate (FDR) is of primary importance, while a low false negative rate (FNR) is a complementary measure. The lasso is a popular selection method in Cox regression, but its results depend heavily on the penalty parameter λ. Usually, λ is chosen using maximum cross-validated log-likelihood (max-cvl). However, this method has often a very high FDR. We review methods for a more conservative choice of λ. We propose an empirical extension of the cvl by adding a penalization term, which trades off between the goodness-of-fit and the parsimony of the model, leading to the selection of fewer biomarkers and, as we show, to the reduction of the FDR without large increase in FNR. We conducted a simulation study considering null and moderately sparse alternative scenarios and compared our approach with the standard lasso and 10 other competitors: Akaike information criterion (AIC), corrected AIC, Bayesian information criterion (BIC), extended BIC, Hannan and Quinn information criterion (HQIC), risk information criterion (RIC), one-standard-error rule, adaptive lasso, stability selection, and percentile lasso. Our extension achieved the best compromise across all the scenarios between a reduction of the FDR and a limited raise of the FNR, followed by the AIC, the RIC, and the adaptive lasso, which performed well in some settings. We illustrate the methods using gene expression data of 523 breast cancer patients. In conclusion, we propose to apply our extension to the lasso whenever a stringent FDR with a limited FNR is targeted. Copyright © 2016 John Wiley & Sons, Ltd.

Alphas, betas and skewy distributions: two ways of getting the wrong answer

Although many parametric statistical tests are considered to be robust, as recently shown in Methodologist’s Corner, it still pays to be circumspect about the assumptions underlying statistical tests. In this paper I show that robustness mainly refers to α, the type-I error. If the underlying distribution of data is ignored there can be a major penalty in terms of the β, the type-II error, representing a large increase in false negative rate or, equivalently, a severe loss of power of the test.

Syphilis in HIV-infected patients

Syphilis may facilitate the acquisition and transmission of human immunodefieieney virus (HIV).As a result of immune system suppression.the coupe of syphilis in HIV-infected patients difiers from that in non-HIV-infected patients.Syphilis in HIV-infected patients may be associated with some atypical and severe clinical manifestations,a rapid progression and an increase in false-negative rate for syphilis serum reaction,incidence of neurosyphilis,serum recurrence and in treatment failure with benzathine penicillin.Besides,the progression to cardiovascular syphilis may be accelerated in HIV-infected syphilic patients. Key words: Syphilis; HIV; Infection

Performance measures of the illiterate E-chart vision-screening test used in Northern District Israeli school children

To evaluate the screening performance of 6/6 and 6/12 vision cut-offs with an illiterate E-chart implemented by a public health nurse to test children for ocular abnormalities and uncorrected refractive error. The gold standard diagnosis is an eye examination performed by an ophthalmologist. A cross-sectional population-based study was conducted among 2113 students' ages 6-7 and 13-14 years old in 70 Northern District Israeli schools. Students were tested by nurses and ophthalmologists. A nurse examination was carried out using the illiterate E-chart for vision measurement. The medical examination included vision history, clinical eye examination, vision and retinoscopy testing. The Physician's evaluation of whether students needed a referral for diagnostic procedures, treatment and/or follow-up was recorded. Screening test's performance was determined using ophthalmologist's decision regarding referral as the gold standard. Detection rate (DR), false-positive rate (FPR), odds affected positive result (OAPR), positive predictive value (PPV) and negative predictive value (NPV) were estimated overall and by students' demographic characteristics. For vision >6/6 cut-off in at least one eye (eyes tested separately): DR - 71.9% (95% CI 65.8-78.7%), FPR - 22.8% (95% CI 17.9-28.9%), OAPR - 0.98:1 (95% CI 0.84:1-1.15:1), PPV - 52.7% (95% CI 45.4-61.2%), NPV - 90.9% (95% CI 88.7-93.1%). For 6/12 vision cut-off, namely vision 6/12 or worse in both eyes (tested separately): DR - 58.6 (95% CI 51.8-66.4%), FPR - 15.2% (95% CI 10.9-21.1%), OAPR - 1.13:1 (95% CI 0.94:1-1.35:1), PPV - 61.1% (95% CI 52.9-70.6%), NPV - 87.6% (95% CI 84.9-90.4%). Vision-screening test performance measures are mild. It is suggested to change vision cut-off level that denotes vision abnormality from current policy of vision not equal 6/6 in both eyes (tested separately) to vision 6/12 or worse in both eyes (tested separately). This change will result in reduction of FPR from 22% to 15%, concomitant with an increase in false-negative rate from 28% to 41%. Students may be equally screened by either a senior or a less experienced nurse.

A simple method for evaluating the safety of high-yield criteria

High-yield criteria for selecting patients for further investigation or treatment sometimes may be associated with an increase in the false-negative rate (decrease in sensitivity), when compared with conventional methods of selection. A simple method, suitable for use by nonstatisticians, is presented. It enables the determination of the sample size required to measure the false-negative rate to a given degree of precision, or the smallest increase in false-negative rate that a study of a given size is likely to detect. Examples of use are provided.

A Prescreening Device for Cancer of the Uterus

A prescreening device for cancer of the uterus was based on the slower sedimentation rate of cells from a vaginal aspirate in the presence of cancer than in its absence. The apparatus recorded the increase in light transmission through the test tube as the cells fell. This mechanical examination of the rate of fall of vaginal and cervical cells did not diagnose cancer, but it identified the normal specimens free of cancer or infections. The negative specimens comprised the bulk of diagnostic material. There was a small increase in false-negative rate compared with the false-negative rate in standard cytologic tests, but this was counterbalanced by the increase in the number of specimens examined.