False-positive Test Results Research Articles

Content and specificity of the Anti-SARS-CoV-2 antibodies in solutions for immunoglobulin replacement therapy

BackgroundSpecific antibodies are important for post-vaccination and post-infection immune responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The role of antibodies in preventing and treating Coronavirus disease 2019 (COVID-19) in high-risk populations has been highlighted through the use of virus-specific monoclonal antibodies, which has raised the question of immunoglobulin replacement therapy (IRT) used in immunocompromised patients. MethodsVirus-specific anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NCAP) antibodies (assessed using a chemiluminescence assay and virus-neutralizing antibodies (virus neutralization test against Delta and Omicron variants)) were analyzed in 20 batches of 10 % (100 mg/mL) immunoglobulin solutions for intravenous IRT from two commercially available producers between January 2022 and March 2023 for clinical use. ResultsAnti-RBD and anti-NCAP antibodies were detected in all 20 batches of assessed IRT solutions (mean concentrations of 2817 IU/mL and 2380 IU/mL, respectively). Notably, the concentration of the virus-specific antibodies increased continuously during the follow-up period (from 822.5 IU/mL to 4066.4 IU/mL and 102 IU/mL to 3455.9 IU/mL). These antibodies demonstrated high virus-neutralizing activity against the Delta variant (mean titers of 436 and 325) but were limited to the Omicron variant (mean titers 78 and 70). The differences observed between the two brands were not statistically significant. ConclusionIRT solutions contain high concentrations of anti-SARS-CoV-2 specific antibodies, which may prevent COVID-19; however, the efficacy can be influenced by variable virus-neutralizing activities against different viral strains. Therefore, appropriate IRT should be combined with other approaches, such as vaccination or pre- and post-exposure prophylaxis. Passively transmitted specific antibodies may also lead to false-positive serological test results.

'Pitfalls for differentiating basal cell carcinoma from non-basal cell carcinoma on optical coherence tomography: A clinical series'.

Optical coherence tomography (OCT), a non-invasive diagnostic modality, may replace biopsy for diagnosing basal cell carcinoma (BCC) if a high-confidence BCC diagnosis can be established. In other cases, biopsy remains necessary to establish a histopathological diagnosis and treatment regimen. It is, therefore, essential that OCT assessors have a high specificity for differentiating BCC from non-BCC lesions. To establish high-confidence BCC diagnoses, specific morphological BCC characteristics on OCT are used. This study aimed to review several cases of non-BCC lesions that were misclassified as BCC by experienced OCT assessors, thereby providing insight into the causes of these misclassifications and how they may be prevented. The study population consisted of patients who had a histopathologically-verified non-BCC lesion. Patients from Maastricht University Medical Center+ from February 2021 to April 2021 were included in the study. Two independent OCT assessors assessed OCT scans. One OCT assessor recorded the presence or absence of validated morphological BCC characteristics. A false-positive OCT test result was defined as certainty of BCC presence in a non-BCC lesion. The frequency of misclassifications and the presence or absence of morphological BCC features are discussed. A total of 124 patients with non-BCC lesions were included. Six patients were misclassified by both OCT assessors and are discussed in more detail. Histopathological diagnoses were squamous cell carcinoma (n = 2/21), actinic keratosis (n = 2/29), squamous cell carcinoma insitu/Bowen's disease (n = 1/16), or interphase dermatitis (n = 1/4). In all misclassified cases, multiple, apparent morphological BCC characteristics on OCT were present. Most non-BCC lesions are recognized as such by OCT assessors. However, there remains a small risk that a high-confidence BCC diagnosis is established in non-BCC lesions wherein features mimicking validated BCC characteristics are present. Misclassification may be prevented by careful delineation of epidermal layers and good differentiation between dermal ovoid structures typical of BCC versus squamous cell carcinoma.

The dexamethasone assay as a useful tool to identify false positive dexamethasone screening test results

The dexamethasone assay as a useful tool to identify false positive dexamethasone screening test results

False-positive Aspergillus galactomannan immunoassay in the glucose component of total parenteral nutrition products.

In October 2022, we experienced a significant increase in samples showing high galactomannan (GM) indexes ranging from 6.22 to 10.58, as determined by the Platelia Aspergillus antigen immunoassay, also known as the GM test. After reviewing the medical records of nine GM antigenemia cases that did not show evidence of invasive aspergillosis, we found that these patients had received total parenteral nutrition (TPN) products from the same manufacturer, whose supplier of the glucose component had recently changed. The TPN products supplied by the specific manufacturer in October were subjected to a GM assay. The glucose component of the products from three different lot numbers exhibited strong positive results in the GM assay. Microbiological investigations through fungal culture and PCR on the TPN products were negative. The present study demonstrated that the glucose component of the TPN products contained a high level of GM antigen, which caused false-positive GM test results. The source of GM in the glucose component was glucoamylase, which was produced from Aspergillus niger to obtain glucose monohydrate from starch. Investigation of three commercially available glucoamylase products exhibited positive GM and 1,3-β-D-glucan tests with various titers positive up to 1:1,000 dilutions, while fungal cultures were all negative. Quality assurance measures of TPN products to prevent GM contamination should be emphasized during the manufacturing process to avoid unnecessary additional diagnostic procedures and overtreatment of invasive aspergillosis due to false-positive GM tests.IMPORTANCEThis manuscript describes an occurrence of false-positive GM tests in patients receiving TPN products from a manufacturer who had recently changed the supplier of the glucose component. We describe the clinical presentation of nine false-positive cases and the results of serologic and microbiological investigations of the TPN products suspected of contamination with GM. Attempts to detect GM in parenteral nutrition products were made since the detection of GM in sodium gluconate-containing solutions in 2007, but none of them identified the source of elevated GM indexes in TPN products. However, the present study demonstrated that the glucose component of the TPN products contained a high level of GM antigen, which caused false-positive GM assay results. The source of GM was glucoamylase, which was derived from A. niger in the manufacturing process. Physicians and clinical microbiology laboratories should be aware of this issue to improve interpretation and patient care.

Common Causes of False Positive and False Negative Results in Amphetamine Screening Tests

Abstract: The need for toxicological screening of amphetamine users is growing in parallel with its increasing abuse. At the same time, it turns out that these substances most often give false results in rapid drug immunoassay. Therefore, the aim of the present work was to investigate the sources of false positive or false negative results. For this purpose, an analysis of the literature sources in the databases of Google Scholar, PubMed, and Science Direct, was made. The results showed that a number of prescription or OTC medications can cause false positive results due to cross-reactivity (ephedrine, pseudoephedrine, labetalol, metoprolol, some antidepressants, metformin, ranitidine, ofloxacin, selegiline, etc.). In this regard, alternative medications for patients who often have to undergo such screening have been proposed. Some possibilities of unintentionally or intentionally inducing false negative results have also been highlighted. Popular approaches to fooling the screening test are diluting the urine, adding adulterants (marketed products or homemade chemicals), and providing foreign or synthetic urine. Summarizing the possible sources of errors in drug screening is expected to objectify the interpretation of the obtained results.

A-014 Analytical Outlier Occurrence and False Positivity Rate of the Beckman Coulter Access High-sensitivity Cardiac Troponin I Assay

Abstract Background Cardiac troponin (cTn) is the preferred biomarker for the diagnosis of acute myocardial infarction due to its high sensitivity and specificity relative to other available cardiac markers. Accurate measurement is therefore paramount to proper risk stratification of patients. Analytical outliers and false positive results have been previously reported on various platforms though the exact cause remains unknown. These false positive test results may pose a risk for the misclassification of patients and lead to adverse clinical outcomes. We evaluated the performance of the Beckman Coulter Access high-sensitivity cTn I method by measuring the occurrence of analytical outliers between duplicate results and the false positivity rate (i.e., fliers). Methods We tested 2535 samples from 1879 patients in duplicate on the Beckman Coulter Access hs-cTn I assay. These specimens had initial troponin measurements above the gender-specific 99th percentile of the upper reference limit (URL) cutoff and were immediately aliquoted, re-centrifuged, and re-tested. Non-reproducible results (outliers) were defined as having a concentration difference between the replicates exceeding 10%. Critical outliers were defined as duplicate results with concentrations that differed by greater than 10% from the initial result and the second result was classified in a lower risk stratification category than the original result. Results Approximately 12% (305) of the positive samples tested in duplicate had a percent difference that was >10% and therefore did not meet the recommended precision requirements of the assay. Of these specimens, 33 (10.8%) were classified as critical outliers because the repeat test result crossed a critical decision limit threshold. For sixteen samples the risk classification for the patient was downgraded from high (>50 ng/L) to moderate risk (13–50 ng/L (F); 20–50 ng/L (M)). Seventeen false positive results were identified in which the patients were downgraded from the high to low risk category (<13 ng/L (F); <20 ng/L (M)). Nearly 85% of the samples identified as outliers were lithium heparinized plasma. Conclusion We evaluated the reproducibility of the Beckman Coulter Access hs-cTn I method across 11 hospitals in an integrated healthcare network to characterize the occurrence of analytical outliers and false positive results. Our data indicated an outlier rate of 12% (305/2535) for positive hs-cTn I results; however, the risk category only changed for 1.3% (33/2535) of positive troponin results upon repeat analysis. Overall the false positivity rate was determined to be <0.1% (n = 55 560).

A-315 Pregnant Women Showed Lower Incidence Rates of False-positive Treponemal Antibody Screening Results When Compared with Nonpregnant Women and Men at an Appalachian Academic Medical Center

Abstract Background Screening for syphilis infection is recommended for all pregnant women and any adult or adolescent with increased risk for infection. Many clinical labs have adopted the reverse syphilis serology testing algorithm, that employs an automated and high-throughput treponemal antibody test as the initial screen followed by a non-treponemal antibody test to confirm all reactive samples. For specimens with discordant results, a second treponemal antibody test is used as the adjudicator. Syphilis serological tests can have false-positive results, causing discordant results between screening test and confirmatory test and complicating result interpretation. It is controversial from the literature whether pregnancy is a cause of false-positive results. This study is to determine the incidence rate of false-positive treponemal screening results among pregnant and nonpregnant patients, and to assess whether false-positivity is associated with pregnancy and age. Methods This is a retrospective study of sequential results from two treponemal antibody screening tests, including BioPlex 2200 Syphilis Total immunoassay between May 2020 and Jan 2022, and Alinity i Syphilis TP assay between Feb 2022 and Nov 2022. For each screening test, the incidence rates of false-positive results were calculated based on the reverse algorithm criteria and compared among pregnant women, nonpregnant women and men. The age differences between patients with false-positive results and patients with nonreactive results were also evaluated. Results Overall, 0.32% of 9 575 samples tested by Alinity assay showed false-positive results not confirmed by RPR or TP-PA. This is significantly lower (P < 0.01) than 0.60% of 14 983 samples observed for BioPlex assay. However, the lower incidence rate of false-positive results for Alinity assay relative to the Bioplex assay is only observed in pregnant women (0.18% vs 0.44%, P < 0.01) and nonpregnant women (0.32% vs 0.71%, P = 0.06), but not in men (0.68% vs 0.63%, P = 0.81). For both assays, male patients with false-positive results had an older median age than those with nonreactive results, and female patients showed the opposite trend, although statistical significance was only observed in nonpregnant women for Bioplex assay (median [IQR], 25 [19–35] vs 30 [22–43], P = 0.047). For both assays, pregnant women had lower incidence rates of false-positive results than nonpregnant women, although the differences did not reach statistical significance without age adjustment (Bioplex assay: 0.44% vs 0.71%, P = 0.07; Alinity assay: 0.18% vs 0.32%, P = 0.26). When age is adjusted, binary logistic regression analysis showed that pregnant women had significantly lower incidence rates of false-positive results relative to nonpregnant women for both assays (BioPlex assay: P = 0.049; Alinity assay: P < 0.01). Conclusion Although the incidence rates of false-positive results in BioPlex and Alinity treponemal antibody screening tests were overall within a low range, a significantly lower rate was observed for Alinity assay in pregnant women but not in men. For both assays, pregnant women showed a significantly lower incidence rate of false-positive results in comparison with nonpregnant women after age adjustment.

Aspergillus-specific IgG antibodies for diagnosing chronic pulmonary aspergillosis compared to the reference standard

ObjectivesTo evaluate the performance of Aspergillus-specific IgG antibodies for diagnosing chronic pulmonary aspergillosis (CPA) by using a cohort of patients with histologically proven CPA as a reference standard. MethodsWe collected Aspergillus-specific IgG antibody titres from patients with histologically proven CPA in collaboration with CPAnet study sites in Denmark, Germany, Belgium, India, Moldova, and Pakistan (N = 47). Additionally, sera from diseased and healthy controls were prospectively collected at the Medical Clinic of the Research Center, Borstel, Germany (n = 303). Aspergillus-specific IgG antibody titres were measured by the ImmunoCAP® assay (Phadia 100, Thermo Fisher Scientific, Uppsala, Sweden). An Aspergillus-specific IgG antibody titre ≥50 mgA/L was considered positive. ResultsUsing patients with histologically proven CPA as the reference standard, the ImmunoCAP® Aspergillus-specific IgG antibody test had a sensitivity and specificity of 85.1% (95% CI: 71.7–93.8%) and 83.6% (95% CI: 78.0–88.3%), respectively. Patients with histologically proven CPA had significantly higher Aspergillus-specific IgG antibody titre with a median of 83.45 mgA/L (interquartile range 38.9–115.5) than all other cohorts (p < 0.001). False-positive test results occurred in one-third of 79 healthy controls. DiscussionOur study results confirm a high sensitivity of the Aspergillus-specific IgG antibody test for the diagnosis of CPA when using patients with histologically proven CPA as a reference standard. However, positive test results should always match radiological findings as false-positive test results limit the interpretation of the test.

IMPACT OF BREAST CANCER SCREENING ON PATIENTS’ SURVIVAL RATE: A LITERATURE REVIEW

Breast cancer is a type of cancer that develops in the breast tissue and is commonly detected, especially in women. Approximately one out of every 10 diagnosed cancer cases is reported as breast cancer. In 2020, there were 2.3 million cases of breast cancer detected, resulting in 685,000 deaths within the same year. Early detection of breast cancer is crucial and can be achieved through various screening programs. These programs utilize different methods, ranging from the simplest and quickest method, which is breast self-examination, to more complex instrument-based methods like mammograms. Screening is the primary tool for detecting breast cancer at an early stage, even before patients experience any symptoms. This early detection allows for more successful and beneficial treatment, increasing the chances of survival and reducing the risk of death from breast cancer. The ultimate goal of breast cancer screening is to detect cancer in its preclinical stage when no symptoms are felt or seen by the patients. This early diagnosis leads to more effective treatment outcomes. According to the American Cancer Society, the 5-year relative survival rate for localized breast cancer, which means the cancer has not spread outside the breast, is 99 percent. It's important to note that different screening options are available, and the choice of the right method depends on factors such as a woman's age, the presence of risk factors, and availability. However, screening also carries some risks, including false-positive test results and overdiagnosis of harmless lesions.

Pre-Operative SARS-CoV-2 Testing in Asymptomatic Heart Transplantation Recipients.

From the start of the coronavirus disease 2019 (COVID-19) pandemic, international guidelines have recommended pre-operative screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before heart transplantation (HTx). Due to the changing prevalence of COVID-19, the chances of false positive results have increased. Because of increased immunity in the population and evolution of SARS-CoV-2 to current Omicron variants, associated mortality and morbidity have decreased. We set out to investigate the yield and side effects of SARS-CoV-2 screening in our center. We performed a retrospective cohort study in the University Medical Center Utrecht. The study period was from March 2019 to January 2023. All data from patients who underwent HTx were collected, including all pre-operative and post-operative SARS-CoV-2 tests. Furthermore, all clinical SARS-CoV-2 tests for the indication of potential HTx were screened. In the period under study, 51 patients underwent HTx. None of the recipients reported any symptoms of a viral infection. Fifty HTx recipients were screened for SARS-CoV-2. Forty-nine out of fifty patients tested negative. One patient had a false positive result, potentially delaying the HTx procedure. There were no cancelled HTx procedures due to a true positive SARS-CoV-2 test result. Pre-operative SARS-CoV-2 screening in asymptomatic HTx recipients did not lead to any true positive cases. In 2% of the cases, screening resulted in a false positive test result. With the current Omicron variants, in combination with a low-prevalence situation, we propose to abandon pre-operative SARS-CoV-2 screening and initiate a symptom-driven approach for the general viral testing of patients who are called in for a potential HTx.

Enhancing Atrial Fibrillation detection accuracy: A wavelet transform filtered single lead ECG signal analysis with artificial neural networks and novel feature extraction

Atrial Fibrillation (AF) is a common cardiac arrhythmia that can lead to fatal outcomes. Detecting AF early is crucial for improving patient outcomes and reducing complications. However, AF is difficult to detect due to asymptomatic cases, false-positive test results, and patient non-adherence. Therefore, it is essential to develop effective methods for early AF detection that can prolong patient life. This study proposes a novel approach for AF detection using a wavelet transform-based filtered ECG signal and a neural network with a novel feature extractor. Firstly, the wavelet transform is applied to filter the ECG signal; secondly, the novel feature extractor is designed to extract important features from the filtered ECG signal. The extracted features are then used as input to a neural network for AF classification. The proposed method is evaluated on two publicly available ECG datasets, and the results show a prominent accuracy of 96% with a ROC is 0.95 and 86% with a ROC is 0.84 for the two datasets, respectively. In addition, to enhance the model’s performance, we have utilized 5-fold cross-validation which achieved an accuracy of 0.99 for Dataset 1 and 0.90 for Dataset 2, respectively. Compared to existing AF detection methods, our approach provides a promising solution that can improve the early diagnosis and treatment of AF. This study presents a new avenue for AF detection and has the potential to advance the field of cardiac arrhythmia detection.

Referral rate and false-positive rates in a hearing screening program among high-risk newborns.

More studies exploring referral rates and false-positive rates are needed to make hearing screening programs in newborns better and cost-effective. Our aim was to study the referral and false-positivity rates among high-risk newborns in our hearing screening program and to analyze the factors potentially associated with false-positive hearing screening test results. A retrospective cohort study was done among the newborns hospitalized at a university hospital from January 2009 to December 2014 that underwent hearing screening with a two-staged AABR screening protocol. Referral rates and false-positivity rates were calculated and possible risk factors for false-positivity were analyzed. 4512 newborns were screened for hearing loss in the neonatology department. The referral rate for the two-staged AABR-only screening was 3.8% with false-positivity being 2.9%. Our study showed that the higher the birthweight or gestational ageof the newborn, the lower the odds of the hearingscreening resultsbeing false-positive, and the higher the chronological age of the infant at the time of screening, the higher the odds of the resultsbeing false-positive. Our study did not show a clear association between the mode of delivery or gender and false-positivity. Among high-risk infants, prematurity and low-birthweight increased the rate of false-positivity in the hearing screening, and the chronological age at the time of the test seems to be significantly associated with false-positivity.

Biochemical Assessment of Pheochromocytoma and Paraganglioma.

Pheochromocytoma and paraganglioma (PPGL) require prompt consideration and efficient diagnosis and treatment to minimize associated morbidity and mortality. Once considered, appropriate biochemical testing is key to diagnosis. Advances in understanding catecholamine metabolism have clarified why measurements of the O-methylated catecholamine metabolites rather than the catecholamines themselves are important for effective diagnosis. These metabolites, normetanephrine and metanephrine, produced respectively from norepinephrine and epinephrine, can be measured in plasma or urine, with choice according to available methods or presentation of patients. For patients with signs and symptoms of catecholamine excess, either test will invariably establish the diagnosis, whereas the plasma test provides higher sensitivity than urinary metanephrines for patients screened due to an incidentaloma or genetic predisposition, particularly for small tumors or in patients with an asymptomatic presentation. Additional measurements of plasma methoxytyramine can be important for some tumors, such as paragangliomas, and for surveillance of patients at risk of metastatic disease. Avoidance of false-positive test results is best achieved by plasma measurements with appropriate reference intervals and preanalytical precautions, including sampling blood in the fully supine position. Follow-up of positive results, including optimization of preanalytics for repeat tests or whether to proceed directly to anatomic imaging or confirmatory clonidine tests, depends on the test results, which can also suggest likely size, adrenal vs extra-adrenal location, underlying biology, or even metastatic involvement of a suspected tumor. Modern biochemical testing now makes diagnosis of PPGL relatively simple. Integration of artificial intelligence into the process should make it possible to fine-tune these advances.

Limited Utility of Toxicology Testing at Delivery for Perinatal Cannabis Use.

To describe the characteristics of individuals undergoing toxicology testing at delivery for a sole indication of cannabis use and to evaluate the rate of unexpected positive toxicology testing results among this cohort. This retrospective cohort study included dyads with a maternal history of cannabis use who underwent peripartum toxicology testing between 2016 and 2020 at 5 birthing hospitals in Massachusetts. We collected information on maternal demographic characteristics and toxicology test results and reviewed records of dyads with unexpected positive results to identify additional social risk factors and clinical outcomes. Of 60 608 live births reviewed, 1924 dyads underwent toxicology testing, including 614 (31.9%) for a sole indication of cannabis use. Significantly greater percentages of patients in the cannabis cohort were <25 years old (32.4% vs 6.1% of the birthing population, P <.001), non-Hispanic Black (32.4% vs 8.1%, P < .001), Hispanic or Latino (30.5% vs 15.5%), American Indian/Alaskan (0.7% vs 0.1%), and publicly insured (39.9% vs 15.6%, P <.001). Eight of the 614 dyads (1.3%) had an unexpected positive toxicology test result, including 2 (0.3%) unexpectedly positive for opioids. Seven dyads (1.1%) had false positive test results for unexpected substances. Only 1 test result changed clinical management; a urine test positive for opioids prompted monitoring (but not medication) for neonatal opioid withdrawal syndrome. Toxicology testing of patients for a sole indication of cannabis use, without other risk factors, may be of limited utility in elucidating other substance use and may exacerbate existing disparities in perinatal outcomes.

The Diagnostic Test: Goodness, Characteristics, and Interpretation: Under the Impact of the Corona Pandemic and Different SARS-CoV-2 Tests

Many diagnostic tests are currently being performed around the world to detect SARS-CoV-2 infection. Positive and negative test results are not one hundred percent accurate, but have far-reaching consequences. There are false positives (test positive, uninfected) and false negatives (test negative, infected). A positive/negative result does not necessarily mean that the test subject is actually infected/non-infected. This article has two objectives: 1. to explain the most important characteristics of diagnostic tests with binary outcome 2. to point out problems and phenomena of interpretation of diagnostic tests, on the basis of different scenarios. Presentation of the basic concepts of the quality of a diagnostic test (sensitivity, specificity) and pre-test probability (prevalence of test group). Calculation (including formulas) of further important quantities. In the basic scenario, sensitivity is 100%, specificity 98.8%, and pre-test probability of 1.0% (10 infected persons per 1,000 tested). For 1,000 diagnostic tests, the statistical mean is 22 positive cases, 10 of which are true-positive. The positive predictive probability is 45.7%. The prevalence calculated from this (22/1,000 tests) overestimates the actual prevalence (10/1,000 tests) by a factor of 2.2. All cases with a negative test outcome are true negative. The prevalence has a strong influence on the positive and negative predictive value. This phenomenon occurs even with otherwise very good test values of sensitivity and specificity. At a prevalence of only 5 infected persons per 10,000 (0.05%), the positive predictive probability drops to 4.0%. Lower specificity amplifies this effect, especially with small numbers of infected persons. If the sensitivity or specificity is below 100%, diagnostic tests are always error-prone. If the prevalence of infected persons is low, a large number of false positive results are to be expected - even if the test is of good quality with a high sensitivity and especially a high specificity. This is accompanied by low positive predictive values, i. e. positive tested persons are not infected. A false positive test result in the first test can be clarified by carrying out a second test.

Estimating the lifetime risk of a false positive screening test result.

False positive results in screening tests have potentially severe psychological, medical, and financial consequences for the recipient. However, there have been few efforts to quantify how the risk of a false positive accumulates over time. We seek to fill this gap by estimating the probability that an individual who adheres to the U.S. Preventive Services Task Force (USPSTF) screening guidelines will receive at least one false positive in a lifetime. To do so, we assembled a data set of 116 studies cited by the USPSTF that report the number of true positives, false negatives, true negatives, and false positives for the primary screening procedure for one of five cancers or six sexually transmitted diseases. We use these data to estimate the probability that an individual in one of 14 demographic subpopulations will receive at least one false positive for one of these eleven diseases in a lifetime. We specify a suitable statistical model to account for the hierarchical structure of the data, and we use the parametric bootstrap to quantify the uncertainty surrounding our estimates. The estimated probability of receiving at least one false positive in a lifetime is 85.5% (±0.9%) and 38.9% (±3.6%) for baseline groups of women and men, respectively. It is higher for subpopulations recommended to screen more frequently than the baseline, including more vulnerable groups such as pregnant women and men who have sex with men. Since screening technology is imperfect, false positives remain inevitable. The high lifetime risk of a false positive reveals the importance of educating patients about this phenomenon.

Net benefit of diagnostic tests for multistate diseases: an indicator variables approach

ABSTRACT A limitation of the common measures of diagnostic test performance, such as sensitivity and specificity, is that they do not consider the relative importance of false negative and false positive test results, which are likely to have different clinical consequences. Therefore, the use of classification or prediction measures alone to compare diagnostic tests or biomarkers can be inconclusive for clinicians. Comparing tests on net benefit can be more conclusive because clinical consequences of misdiagnoses are considered. The literature suggested evaluating the binary diagnostic tests based on net benefit, but did not consider diagnostic tests that classify more than two disease states, e.g., stroke subtype (large-artery atherosclerosis, cardioembolism, small-vessel occlusion, stroke of other determined etiology, stroke of undetermined etiology), skin lesion subtype, breast cancer subtypes (benign, mass, calcification, architectural distortion, etc.), METAVIR liver fibrosis state (F0- F4), histopathological classification of cervical intraepithelial neoplasia (CIN), prostate Gleason grade, brain injury (intracranial hemorrhage, mass effect, midline shift, cranial fracture) . Other diseases have more than two stages, such as Alzheimer's disease (dementia due to Alzheimer's disease, mild cognitive disability (MCI) due to Alzheimer's disease, and preclinical presymptomatics due to Alzheimer's disease). In diseases with more than two states, the benefits and risks may vary between states. This paper extends the net-benefit approach of evaluating binary diagnostic tests to multi-state clinical conditions to rule-in or rule-out a clinical condition based on adverse consequences of work-up delay (due to false negative test result) and unnecessary workup (due to false positive test result). We demonstrate our approach with numerical examples and real data.

Relationship between False Positive Screening Results of Down Syndrome and Adverse Pregnancy Outcomes.

Maternal serum sample screening in the first and second trimesters has been commonly used to identify women who are at risk of fetal trisomy 21. In addition, these serum markers are associated with adverse perinatal outcomes. Hence, the present study was conducted to determine the relationship between false positive screening results of Down syndrome and adverse pregnancy outcomes. This prospective, two-group, cohort study was conducted on 608 pregnant women who had undergone fetal contingent screening. They were selected through convenience sampling in the twentieth week of pregnancy and were followed up until delivery. The raw Odd Ratios (OR), Relative Risk (RR), and adjusted OR of adverse pregnancy outcomes were calculated in the false positive and true negative groups. The adjusted OR of developing preeclampsia was 1.98 (95%CI: 1.14-3.42), and its RR was 2.13 (95%CI: 1.34-3.38) times higher in the false positive group. Moreover, the adjusted OR of Small for Gestational Age (SGA) was 2.80 (95%CI: 1.76-4.47), and its RR was 2.28 (95%CI: 1.54-3.36) times higher in the false positive group. The adjusted OR of Low Birth Weight (LBW) was 3.34 (95%CI: 1.97-5.64), and its RR was 2.65 (95%CI: 1.72-4.11) times higher in the false positive group. In addition, no significant difference was observed between false positive and true negative groups in terms of preterm birth. Women with a false positive fetal screening test result are more likely to suffer from preeclampsia, SGA, and LBW and require planned prenatal care.

False-positive typhidot IgM assay in COVID-19 patients: A potential public health problem in tropical countries during COVID-19 endemic phase

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, reports of false-positive serological test results were reported in COVID-19 patients. Typhidot IgM test is reported in a few studies to give false-positive results in various viral illnesses in the past. The aim of this study was to estimate the typhidot IgM positivity rate in reverse transcription-polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients. MATERIALS AND METHODS: The present study was a cross-sectional study conducted at a tertiary care hospital. All symptomatic patients having fever that were admitted between April 1, 2021, and July 15, 2021, with a confirmed RT-PCR-positive result for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were included in the study. Serological testing was done by typhoid IgM/IgG rapid diagnostic test for all SARS-CoV-2 RT-PCR-positive patients. The primary outcome studied was to estimate the typhidot IgM positivity rate among RT-PCR-confirmed COVID-19 patients. The secondary outcome studied was to determine the correlation between SARS-CoV-2 RT PCR cycle threshold (CT) value and typhidot-positive result. RESULTS: Three hundred and five (17.99%) out of 1695 samples of confirmed COVID-19 patients were positive for typhoid serology by typhidot IgM test. However, upon performing Point-Biserial correlation analysis (P = 0.832, r = 0.021), no correlation was seen between RT-PCR CT value and typhidot result. CONCLUSIONS: Typhidot test is a nonspecific diagnostic test for typhoid fever which can be false positive in COVID-19 patients. Hence, physicians should take this into consideration to avoid misdiagnosis and delay in accurate treatment of acute febrile illness cases, especially in the present scenario of COVID-19 endemicity.

HPV typing as the method of choice in the prevention and early detection of cervical cancer

Background: Human papillomavirus (HPV) is recognized as the primary cause of cervical cancer (CC), and significant coexisting factors have also been identified. CC is considered a curable disease because it has a long preinvasive period. It is possible to organize effective screening, and the treatment of preinvasive lesions is successful. Aim: To show the importance of HPV typing in the early detection of premalignant cervical disease. Method: Literature review, synthesis, and extraction of key professional and contemporary literature. Results: Depending on the methods used in identification, the presence of different types of HPV was identified in about 90% of intraepithelial neoplasia and CC samples. HPV genotyping plays an important role in the detection of dysplasia and helps to reduce the number of false-positive Pap test results. Randomized controlled trials have shown that CC screening with HPV testing offers greater protection against cervical precancer and cancer compared with cytology-based screening. To date, it has been proven that HPV 16 and 18 genotypes have the highest oncogenic potential. These two genotypes are responsible for about 70% of all squamous cell carcinomas, 30-40% of vulvar cancers, and about 85% of cervical adenocarcinomas. According to a recent report, 48 (35%) of 139 countries recommended HPV-based cervical screening, with most currently switching from cytology to HPV testing. Conclusion: HPV typing can be of great benefit in the early detection of malignant transformation of infected cells and the prevention of CC.