Proportion Of False Negatives Research Articles

Effect of Fluorescence Lymph Node Mapping on Improving Diagnostic Values of CT D3 Lymph Node Staging for Right-Sided Colon Cancer

Background/Objectives: This study evaluated the impact of fluorescence lymph node mapping (FLNM) using indocyanine green (ICG) on the diagnostic accuracy of preoperative computed tomography (CT) in right-sided colon cancer. Methods: A total of 218 patients who underwent laparoscopic right hemicolectomy with D3 lymph node dissection (LND) were analyzed: 86 patients in the FLNM group and 132 in the conventional surgery group. The FLNM technique allowed for enhanced intraoperative visualization of lymph node (LN) and more precise dissection, improving the identification of metastatic LNs. The diagnostic value of preoperative CT staging was assessed in both the FLNM and control groups by calculating the apparent prevalence, true prevalence, sensitivity, specificity, positive predictive value (PPV), negative predictive value, positive likelihood ratio (PLR), negative likelihood ratio, false positive and false negative proportions, and accuracy. Results: FLNM increased the accuracy of CT staging for detecting D3 LN metastasis in advanced cancer cases, with a higher PPV, PLR, and accuracy. In the FLNM group, the false-positive rate was significantly reduced, and the specificity was higher compared to the control group. Multivariate analysis identified FLNM as an independent factor associated with improved D3 LN metastasis detection. These findings suggest that incorporating FLNM into surgical procedures enhances the diagnostic value of preoperative CT by improving the precision of LND, particularly in patients with advanced colon cancer. Conclusions: The use of FLNM for D3 LND enhances the diagnostic accuracy of cN staging in right-sided colon cancer by improving surgical precision.

Histidine-rich protein (hrp) 2-based RDT false-negatives and Plasmodium falciparum hrp 2 and 3 gene deletions in low, seasonal and intense perennial transmission zones in Cameroon: a cross - sectional study.

False negative rapid diagnostic tests (RDTs) accruing to the non-detection of Plasmodium falciparum histidine-rich protein 2/3 (Pfhrp2/3) is threatening the diagnosis and management of malaria. Although regular monitoring is necessary to gauge the level of efficacy of the tool, studies in Cameroon remain limited. This study assessed Plasmodium spp. prevalence and Pfhrp2/3 gene deletions across ecological and transmission zones in Cameroon. This is a cross-sectional, multi-site, community- and hospital- based study, in 21 health facilities and 14 communities covering all five ecological settings in low seasonal (LS) and intense perennial (IPT) malaria transmission zones between 2019 and 2021. Participants were screened for malaria parasite using Pfhrp2 RDT and light microscopic examination of thick peripheral blood smears. DNA was extracted from dried blood spot using chelex®-100 and P. falciparum confirmed using varATS real-time quantitative Polymerase Chain Reaction (qPCR), P. malariae and P. ovale by real-time qPCR of Plasmepsin gene, and P. vivax using a commercial kit. Isolates with amplified Pfcsp and Pfama-1 genes were assayed for Pfhrp 2/3 gene deletions by conventional PCR. A total of 3,373 participants enrolled, 1,786 Plasmodium spp. infected, with 77.4% P. falciparum. Discordant RDT and qPCR results (False negatives) were reported in 191 (15.7%) P. falciparum mono-infected samples from LS (29%, 42) and IPT (13.9%, 149). The Pfhrp2+/Pfhrp3 + genotype was most frequent, similar between LS (5.5%, 8/145) and IPT (6.0%, 65/1,076). Single Pfhrp2 and Pfhrp3 gene deletions occurred in LS (0.7%, 1/145 each) and IPT (3.6%, 39/1,076 vs. 2.9%, 31/1,076), respectively. Whilst a single sample harboured Pfhrp2-/Pfhrp3- genotype in LS, 2.4% (26/1,076) were double deleted at IPT. Pfhrp2+/Pfhrp3- (0.3%, 3/1,076) and Pfhrp2-/Pfhrp3+ (1.2%, 13/1,076) genotypes were only observed in IPT. Pfhrp2, Pfhrp3 deletions and Pfhrp2-/Pfhrp3- genotype accounted for 78.8% (26), 69.7% (23) and 63.6% (21) RDT false negatives, respectively. Plasmodium falciparum remains the most dominant and widely distributed Plasmodium species across transmission and ecological zones in Cameroon. Although the low prevalence of Pfhrp2/3 gene deletions supports the continued use of HRP2-based RDTs for routine malaria diagnosis, the high proportion of false-negatives due to gene deleted parasites necessitates continued surveillance to inform control and elimination efforts.

The steatosis-associated fibrosis estimator (SAFE) outperformed the FIB-4 score in screening the population for liver disease

Assessing fibrosis risk noninvasively is essential. The steatosis-associated fibrosis estimator (SAFE) score shows promise but needs validation. This was a three-part study. In part 1, we compared the SAFE score with the Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) in the National Health and Nutrition Examination Survey (NHANES) cohort (2017-2020), using transient elastography (TE) as screening reference. In part 2, we examined patients who underwent liver biopsies at an Asian center between 2018 and 2020 to assess these models in various liver diseases. In part 3, the SAFE score was applied to adults in the NHANES cohort (1999-2016) to assess the correlation with mortality. In part 1, we studied 6,677 patients, comprising 595 screening positive (TE ≥8 kPa). SAFE (cutoff 100) displayed a lower proportion of false positives (10.4 %) than FIB-4 (cutoff 1.3) and NFS (cutoff -1.455) (22.1 % and 43.6 %) while retaining a low proportion of false negatives (5.5 %). In part 2, SAFE outperformed FIB-4 (P = 0.04) and NFS (P = 0.04) in staging significant fibrosis (≥S2) in NAFLD and had similar accuracies in other etiologies. In part 3, the FIB-4, NFS, and SAFE score were associated with all-cause mortality in the general population, with c-statistics of 0.738, 0.736, and 0.759, respectively. The SAFE score reduced futile referrals more effectively than FIB-4 without raising the missed TE ≥ 8 kPa rate. It correlated with all-cause mortality in the general population and excelled in staging significant fibrosis in NAFLD.

Ovarian-Adnexal Reporting & Data System (O-RADS) versus modified benign descriptors and IOTA ADNEX (two-step strategy) in classification of ovarian masses.

e17569 Background: The use of a single and common language in the diagnosis of ovarian tumors is a multidisciplinary effort spanning several decades that has allowed the global adoption of the Ovarian-Adnexal Reporting & Data System (O-RADS) and the International Ovarian Tumor Analysis (IOTA). The objective is to determine the diagnostic accuracy of O-RADS versus modified benign descriptors and IOTA ADNEX in the classification of adnexal masses. Methods: Ambispective diagnostic accuracy study based on ultrasound data collected at a university hospital with a gynecologic oncology unit between 2012 and 2022. Two IOTA-certified level III sonographers classified adnexal masses using modified benign descriptors (MBD). The main outcome was the classification of the masses as benign or malignant for each strategy. Histopathology was used as the diagnostic reference standard. A diagnostic test analysis was performed. Results: 876 patients with 902 adnexal masses were included in the study for both analysis strategies. For the two-step analysis, 573 (64%) met the classification criteria for their evaluation based on MBD (first step) and 329 (36%) were assessed using IOTA ADNEX. 99% (567/573) of the masses classified according to the MBD, were benign by histopathology. The diagnostic performance of IOTA ADNEX (second step) had a sensibility of 93%, specificity of 64%, positive predictive value of 48%, negative predictive value of 96%, AUC (0,880). Regarding the analysis of the O-RADS system to stratify malignancy risk, we observed a prevalence of 58% for O-RADS 2, 22% for O-RADS 3, 11% for O-RADS 4, and 9% for O-RADS 5. Sensibility was 92%, specificity 88%, positive predictive value 48%, negative predictive value del 99%, AUC (0,886). Conclusions: In our experience, the diagnostic accuracy of the two-step strategy or the O-RADS system is similar. However, the ORADS system had a lower proportion of false negatives.

Adjusted norovirus molecular epidemiology pattern among the children with acute gastroenteritis: A study from a tropical country

Objective: People of all ages can get acute viral gastroenteritis, which is a frequent illness. In immunocompromised individuals, the viral etiology of acute gastroenteritis (AGE) can cause long-term diarrhea. The detection of viruses may be done very well using molecular approaches. Molecular approaches are essential for the genetic characterization of cocirculating strains and also serve as diagnostic tools. Quantitative polymerase chain reaction (qPCR), which has been shown to be more specific than enzyme-linked immunosorbent assay (ELISA), is the current gold standard. There is growing fear, nevertheless, that qPCR will produce a sizable proportion of false negatives. Materials and Methods: The authors of this work reevaluate the information on enteric norovirus molecular epidemiology in children in a tropical Indochina nation and look at the role of intestinal noroviruses in AGE. Results: The results of this investigation suggest that the precise incidence rate in the tropical environment under consideration may be very high. Regardless of age, the norovirus can be found in local youngsters. Conclusion: The relationship between norovirus and gastrointestinal sickness in this condition has to be thoroughly researched due to the high frequency of norovirus in the stool samples of the tested children, regardless of AGE. Norovirus is the most common cause of AGE, however, other infections may exist and go undetected or misdiagnosed.

Significance of carcinoembryonic antigen detection in the early diagnosis of colorectal cancer: A systematic review and meta-analysis.

Colorectal cancer (CRC) is a prevalent malignant tumor involving adenomas that develop into malignant lesions. Carcinoembryonic antigen (CEA) is a non-specific serum biomarker upregulated in CRC. The concentration of CEA is modulated by tumor stage and grade, tumor site in the colon, ploidy status, and patient smoking status. This study aimed to evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults. To evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults. A systematic search was performed using four databases: MEDLINE, Cochrane Trials, EMBASE, and the Web of Science. The inclusion criteria were as follows: Adult patients aged ≥ 18 years who had completed CRC curative treatment and were followed up postoperatively; reporting the number of CRC recurrences as an outcome; and randomized, clinical, cohort, and case-control study designs. Studies that were not published in English and animal studies were excluded. The following data were extracted by three independent reviewers: Study design, index tests, follow-up, patient characteristics, and primary outcomes. All statistical analyses were performed using the RevMan 5.4.1. A total of 3232 studies were identified, with 73 remaining following the elimination of duplicates. After screening on predetermined criteria, 12 studies were included in the final analysis. At a reference standard of 5 mg/L, CEA detected only approximately half of recurrent CRCs, with a pooled sensitivity of 59% (range, 33%-83%) and sensitivity of 89% (range, 58%-97%). CEA is a significant marker for CRC diagnosis. However, it has insufficient sensitivity and specificity to be used as a single biomarker of early CRC recurrence, with an essential proportion of false negatives.

Desempeño en la Detección de Nódulos Mamarios del Examen Clínico de Seno Realizado por Examinadoras Invidentes Comparado con Ultrasonido

Abstract. Introduction: Clinical examination of the breast is a simple method to detect nodules, which is useful to determine its nature, of low cost, non-invasive and of great value as a diagnostic tool when necessary. Traditionally, clinical examination is carried out by trained health personnel with a sensitivity of 54% and a specificity of 94%; it is unknown its usefulness compared to mammography, since the physical examination in patients without previous screening has not been evaluated. Objective: to determine the performance of the clinical examination of tactile auxiliary examiners for detecting mammary nodules, compared with the ultra-sonography findings in the detection of mammary nodules. Methods: a validation study of diagnostic tests was carried out with a random sample of 325 women from the San Juan de Dios Hospital, aged between 18 and 70 years, during a period of 2 months. Results: The sensitivity was 64.8% (95% CI 57.5-71); specificity, 45.6% (95% CI 37.8-53.6); positive predictive value, 58.5% (95% CI 51.4-65.1); negative predictive value, 52.3% (95% CI 43.8-60.7). Proportion of false positives, 54.4% (95% CI 46.4-62.2); proportion of false negatives, 35.2% (95% CI 28.6-42.5). Conclusion: The study showed that the clinical examination of the breast by trained personnel with visual impairment is a diagnostic test sensitive to the detection of mammary nodules; but it has little specificity. In addition, it is a complement to screening for mammary pathology, even though it does not replace the medical examination nor the screening tests recommended by the clinical practice guidelines.

Development, Evaluation, and Multisite Deployment of a Machine Learning Decision Tree Algorithm To Optimize Urinalysis Parameters for Predicting Urine Culture Positivity.

PittUDT, a recursive partitioning decision tree algorithm for predicting urine culture (UC) positivity based on macroscopic and microscopic urinalysis (UA) parameters, was developed in support of a broader system-wide diagnostic stewardship initiative to increase appropriateness of UC testing. Reflex algorithm training utilized results from 19,511 paired UA and UC cases (26.8% UC positive); the average patient age was 57.4 years, and 70% of samples were from female patients. Receiver operating characteristic (ROC) analysis identified urine white blood cells (WBCs), leukocyte esterase, and bacteria as the best predictors of UC positivity, with areas under the ROC curve of 0.79, 0.78, and 0.77, respectively. Using the held-out test data set (9,773 cases; 26.3% UC positive), the PittUDT algorithm met the prespecified target of a negative predictive value above 90% and resulted in a 30 to 60% total negative proportion (true-negative plus false-negative predictions). These data show that a supervised rule-based machine learning algorithm trained on paired UA and UC data has adequate predictive ability for triaging urine specimens by identifying low-risk urine specimens, which are unlikely to grow pathogenic organisms, with a false-negative proportion under 5%. The decision tree approach also generates human-readable rules that can be easily implemented across multiple hospital sites and settings. Our work demonstrates how a data-driven approach can be used to optimize UA parameters for predicting UC positivity in a reflex protocol, with the intent of improving antimicrobial stewardship and UC utilization, a potential avenue for cost savings.

Brief Youth Self-Report Screener for Tics: Can a Subscale of the Motor Tic, Obsession and Compulsion, and Vocal Tic Evaluation Survey (MOVES) Identify Tic Disorders in Youth?

ABSTRACT Tics are unwanted, repetitive movements and sounds that frequently present during childhood. They are typically brief and purposeless, but can create significant distress for individuals, and often co-occur with other neuropsychiatric conditions. Thus, early identification of tics is warranted. Unfortunately, tics are often misdiagnosed, and because tics may wax and wane, identification can be difficult, especially in the context of routine clinical visits. There are limited tools that can be used to reliably identify tics in clinical practice, especially in non-specialty settings. The purpose of the current study was to evaluate the performance of the Motor tic, Obsession and compulsion, and Vocal tic Evaluation Survey (MOVES), a self-report scale with some support as a screening tool. In addition, the performance of a subset of questions (the MOVES-6) was evaluated for rapid screening. Participants were recruited across two study sites and included children and adolescents diagnosed with Tourette syndrome (n = 151) or another persistent tic disorder (n = 10) and community controls (n = 74). Results suggest that both MOVES and the MOVES-6 have high sensitivity (90% and 88%, respectively) and at least acceptable specificity (77% and 86%, respectively) compared with expert assessment of tic disorders, suggesting that both versions can identify tic disorders without high proportions of false negatives. Both versions were highly sensitive with acceptable specificity regardless of sex, race/ethnicity, and age. The MOVES and MOVES-6 show promise as a screener for tics or tic disorders, but additional research is needed, particularly in a general population setting.

Performance of Simple Fibrosis Score in Non-Alcoholic Fatty Liver Disease with and without Type 2 Diabetes.

This cross-sectional study enrolled 267 patients with metabolic risk factors and established non-alcoholic fatty liver disease in the prospective cohort. The performance of fibrosis-4 (FIB-4) score (≥1.3) to diagnose advanced fibrosis using transient elastography (liver stiffness measurement [LSM] ≥8 kPa) was analyzed. Comparing patients with type 2 diabetes (T2D, n=87) and without (n=180), not FIB-4, but LSM was significantly higher in T2D (P=0.026). The prevalence of advanced fibrosis was 17.2% in T2D and 12.8% in non-T2D. FIB-4 exhibited higher proportion of false negatives in T2D patients (10.9%) than those without (5.2%). The diagnostic performance of FIB-4 was suboptimal in T2D (area under curve [AUC], 0.653; 95% confidence interval [CI], 0.462 to 0.844) compared to that in non-T2D (AUC, 0.826; 95% CI, 0.724 to 0.927). In conclusion, patients with T2D might be beneficial to conduct transient elastography without screening to avoid missing advanced fibrosis.

Artificial intelligence for assistance of radiology residents in chest CT evaluation for COVID-19 pneumonia: a comparative diagnostic accuracy study.

In hospitals, it is crucial to rule out coronavirus disease 2019 (COVID-19) timely and reliably. Artificial intelligence (AI) provides sufficient accuracy to identify chest computed tomography (CT) scans with signs of COVID-19. To compare the diagnostic accuracy of radiologists with different levels of experience with and without assistance of AI in CT evaluation for COVID-19 pneumonia and to develop an optimized diagnostic pathway. The retrospective, single-center, comparative case-control study included 160 consecutive participants who had undergone chest CT scan between March 2020 and May 2021 without or with confirmed diagnosis of COVID-19 pneumonia in a ratio of 1:3. Index tests were chest CT evaluation by five radiological senior residents, five junior residents, and an AI software. Based on the diagnostic accuracy in every group and on comparison of groups, a sequential CT assessment pathway was developed. Areas under receiver operating curves were 0.95 (95% confidence interval [CI]=0.88-0.99), 0.96 (95% CI=0.92-1.0), 0.77 (95% CI=0.68-0.86), and 0.95 (95% CI=0.9-1.0) for junior residents, senior residents, AI, and sequential CT assessment, respectively. Proportions of false negatives were 9%, 3%, 17%, and 2%, respectively. With the developed diagnostic pathway, junior residents evaluated all CT scans with the support of AI. Senior residents were only required as second readers in 26% (41/160) of the CT scans. AI can support junior residents with chest CT evaluation for COVID-19 and reduce the workload of senior residents. A review of selected CT scans by senior residents is mandatory.

Pediatric whole-body magnetic resonance imaging: comparison of STIR and T2 Dixon sequences in the detection and grading of high signal bone marrow changes

ObjectivesTo compare short time inversion recovery (STIR) and T2 Dixon in the detection and grading of high signal intensity areas in bone marrow on whole-body MRI in healthy children.MethodsProspective study, including whole-body 1.5-T MRIs from 77 healthy children. Two experienced radiologists in consensus identified and graded areas of high bone marrow signal on STIR and T2-weighted (T2W) turbo spin echo (TSE) Dixon images (presence, extension) in two different sessions at an interval of at least 3 weeks. In a third session, a third observer joined the two readers for an additional consensus reading with all sequences available (substitute gold standard).ResultsFour hundred ninety of 545 (89.9%) high signal areas were visible on both sequences, while 27 (5.0%) were visible on STIR only and 28 (5.1%) on T2W Dixon only. Twenty-four of 27 (89%) lesions seen on STIR only, and 25/28 (89%) seen on T2W Dixon only, were graded as mildly increased signal intensity. The proportion of true positive high signal lesions was higher for the T2W Dixon images as compared to STIR (74.2% vs. 68.2%) (p = 0.029), while the proportion of false negatives was lower (25.9% vs. 31.7% (p = 0.035) for T2W Dixon and STIR, respectively). There was a moderate agreement between the T2W Dixon and STIR-based extension scores on a 0–4 scale, with a kappa of 0.45 (95% CI = 0.34–0.56).ConclusionsMost high signal bone marrow changes identified on a 1.5-T whole-body MRI were seen on both STIR and water-only T2W Dixon, underscoring the importance of using identical protocols when following bone-marrow signal changes over time.Key Points• Whole-body MRI is increasingly being used to diagnose and monitor diseases in children, such as chronic non-bacterial osteomyelitis, malignant/metastatic disease, and histiocytosis.• Standardized and validated imaging protocols, as well as reference standards by age for the growing skeleton are lacking.• Prospective single-center study showed that 90% of high signal bone marrow areas identified on a 1.5-T whole-body MRI in healthy children is seen on both STIR and water-only T2W Dixon, while 5% is seen on STIR only and 5% on T2W Dixon only.

Clinical value and cost analysis of the sFlt-1/PlGF ratio in addition to the spot urine protein/creatinine ratio in women with suspected pre-eclampsia: PREPARE cohort study

BackgroundThis study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia.MethodsThis was a prospective cohort study performed in a tertiary referral centre. Based on the combination of PCr (< 30) and sFlt-1/PlGF (≤38) results, four groups were described: a double negative result, group A−/−; a negative PCr and positive sFlt-1/PlGF, group B−/+; a positive PCr and negative sFlt-1/PlGF, group C+/−; and a double positive result, group D+/+. The primary outcome was the proportion of false negatives of the combined tests in comparison with PCr alone in the first week after baseline. Secondary, a cost analysis comparing the costs and savings of adding the sFlt-1/PlGF ratio was performed for different follow-up scenarios.ResultsA total of 199 women were included. Pre-eclampsia in the first week was observed in 2 women (2%) in group A−/−, 12 (26%) in group B−/+, 4 (27%) in group C+/−, and 12 (92%) in group D+/+. The proportion of false negatives of 8.2% [95% CI 4.9–13.3] with the PCr alone was significantly reduced to 1.6% [0.4–5.7] by adding a negative sFlt-1/PlGF ratio. Furthermore, the addition of the sFlt-1/PlGF ratio to the spot urine PCr, with telemonitoring of women at risk, could result in a reduction of 41% admissions and 36% outpatient visits, leading to a cost reduction of €46,- per patient.ConclusionsImplementation of the sFlt-1/PlGF ratio in addition to the spot urine PCr, may lead to improved selection of women at low risk and a reduction of hospital care for women with suspected pre-eclampsia.Trial registrationNetherlands Trial Register (NL8308).

Algorithm for predicting sepsis in newborns with respiratory pathology and perinatal lesions of the central nervous system on mechanical ventilation

BACKGROUND: Predicting sepsis in ventilated neonates remains a challenge in neonatology.&#x0D; AIM: To increase the efficiency of predicting sepsis diagnosis in newborns by developing a decision rule for its development based on decision trees.&#x0D; MATERIALS AND METHODS: This clinical study retrospectively reviewed 200 full-term newborns with respiratory pathology that are admitted to the intensive care unit and are on mechanical ventilation without clinical signs of bacterial infection.&#x0D; Upon admission to the department on days 1, 35, and 20, an enzyme-linked immunosorbent assay determined the plasma concentration of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor-, granulocyte colony-stimulating factor, soluble Fas ligand, fibroblast growth factors, and nitric oxide (NO), and immunophenotyping method determined CD3+CD19, CD3CD19+, CD3+CD4+, CD3+CD8+, CD69+, CD71+, CD95+, HLADR+, CD34+, CD14+, CD3CD56+; lymphocytes expressing AnnexinV-FITC+PI, and AnnexinV-FITC+PI+. The possibility of diagnosing sepsis upon intensive care unit admission was assessed by statistical cluster analysis of the total studied immunological criteria. The method of decision trees in the statistical environment R formed a diagnostic rule for predicting sepsis.&#x0D; RESULTS: Visualization of the cluster analysis results of admitted patients did not exclude the presence of two clusters among them (with and without sepsis, which explain the 60.81% of the point variability).&#x0D; Sepsis prediction rule are as follows: disease progression occurs if on day 1 CD95 is 16.8% and NO is 9.6 mkmol/l or CD95 is 16.8%, CD34 is 0.2%, CD69 is 4.12% or CD95 is 16.8%, CD34 is 0.2%, CD69 is 4.12%, and lymphocytes expressing AnnexinV-FITC+PI is 12.3%. The diagnostic accuracy was 96.00%; sensitivity was 97.00%; specificity was 94.90%; the false-positive proportion of diagnoses was 5.10%; the false-negative proportion of diagnoses was 2.94%; the positive result accuracy was 95.19%; and the negative result was 96.88%. The disease was complicated by bacterial sepsis development on 45 days of observation in 45 newborns.&#x0D; CONCLUSIONS: Significant importance in sepsis development belongs to the prevalence of altered immunocompetent cells over proliferation and endogenous synthesis of nitric oxide. The cumulative determination of CD95+, CD69+, AnnexinV-FITC+PI, CD34+, and plasma nitric oxide concentration helped diagnose sepsis development at the preclinical stage. The obtained results indirectly confirm the relevance of studies on sepsis prevention and treatment by drug correction of apoptosis and inhaled NO.

Field evaluation of COVID-19 rapid antigen test: Are rapid antigen tests less reliable among the elderly?

BACKGROUNDThe global outbreak of coronavirus disease 2019 (COVID-19) leads to the development of accessible and cost-effective rapid antigen-detection tests (RATs), as quick and accurate diagnosis is crucial to curb the pandemic. AIMTo evaluate the Humasis COVID-19 Ag Test (Humasis Co., Ltd., Gyeonggi-do, Republic of Korea) in the diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).METHODSThis retrospective study was carried out at the Croatian Institute of Public Health and included patients with clinical symptoms of COVID-19 lasting no longer than 5 d prior to testing, whose nasopharyngeal swabs were primarily tested with RAT. Negative RAT samples underwent confirmatory real-time reverse transcription-polymerase chain reaction (RT-PCR). Diagnostic efficacy was determined compared to RT-PCR. The patients were divided into three age groups (< 18, 19-65, > 65 years). Statistical analysis was performed with the significance level set at P < 0.05.RESULTSIn total, 2490 symptomatic patients were tested; 953 samples were positive on RAT, and 1537 were negative. All negative RAT samples were subjected to RT-PCR; 266 samples were positive and marked as false-negative results on RAT. The calculated negative predictive value as a measure of RAT efficacy was 82.69%. The χ2 test and Kruskal-Wallis test showed a significant difference in the proportion of false negatives (P < 0.001) and RT-PCR cycle (Ct) values for false-negative RATs (P = 0.012) among the age groups. The young age group was significantly less likely to be false negative, whereas the false negatives from the elderly group experienced significantly lower Ct values than the other two age groups.CONCLUSIONEvaluated RAT demonstrated satisfactory performance with more reliable results in younger patients. Humasis COVID-19 Ag RAT is potentially a valuable tool in areas where access to molecular methods is limited; however, RT-PCR remains a gold standard for SARS-CoV-2 detection.

Confirmation value of Western blotting in detecting anti-treponema pallidum specific antibodies with suspicious results

BackgroundDue to the inconsistent results of anti-treponema pallidum (TP) specific antibodies by enzyme-linked immunosorbent assay (ELISA) and Treponema pallidum granule agglutination assay (TPPA) in clinical work, there will be a certain proportion of false-positives and false-negatives depending on TPPA as confirmation results. This study aimed to evaluate the necessity of Western blotting (WB) in samples with inconsistent results in detecting anti-TP antibodies by ELISA and TPPA.MethodsSpecific anti-TP test results in our clinical laboratory were retrospectively analyzed. The specimens with a positive or a negative result, but with colored ELISA plates, were retested by TPPA. WB was used to confirm the suspicious results between ELISA and TPPA. The Chi-square test was used to analyze whether the difference was statistically significant.ResultsA total of 106,757 anti-TP specimens were screened by ELISA from August 2018 to December 2019; 3972 were retested by TPPA, and 3809 were positive by TPPA. ELISA and TPPA showed different results in 163 specimens. Among them, 29 specimens were negative and 134 were positive by ELISA; 76 were negative, 23 were positive, and 64 were “reserve” by TPPA; 93 were negative, 31 were positive, and 39 were suspicious by the WB confirmation test. Compared with WB, the difference in the results of ELISA and TPPA was statistically significant.ConclusionsTPPA is an effective retest method for anti-TP antibody detection. If the results of anti-TP antibodies by ELISA and TPPA are inconsistent, it is necessary to use WB for confirmation.Trial registration This retrospective analysis is in accordance with the ethical guidelines of China and approved by the second hospital of Jiaxing (jxey-2018048).

Validity of Methods to Identify Individuals With Lower Extremity Amputation Using Department of Veterans Affairs Electronic Medical Records

To determine the positive predictive value (PPV) of algorithms to identify patients with major (at the ankle or more proximal) lower extremity amputation (LEA) using Department of Veterans Affairs electronic medical records (EMR) and to evaluate whether PPV varies by sex, age, and race. We conducted a validation study comparing EMR determined LEA status to self-reported LEA (criterion standard). Veterans who receive care at the Department of Veterans Affairs. We invited a national sample of patients (N=699) with at least 1 procedure or diagnosis code for major LEA to participate. We oversampled women, Black men, and men ≤40 years of age. Not applicable. We calculated PPV estimates and false negative percentages for 7 algorithms using EMR LEA procedure and diagnosis codes relative to self-reported major LEA. A total of 466 veterans self-reported their LEA status (68%). PPVs for the 7 algorithms ranged from 89% to 100%. The algorithm that required a single diagnosis or procedure code had the lowest PPV (89%). The algorithm that required at least 1 procedure code had the highest PPV (100%) but also had the highest proportion of false negatives (66%). Algorithms that required at least 1 procedure code or 2 or more diagnosis codes 1 month to 1 year apart had high PPVs (98%-99%) but varied in terms of false negative percentages. PPV estimates were higher among men than women but did not differ meaningfully by age or race, after accounting for sex. PPVs were higher if 1 procedure or at least 2 diagnosis codes were required; the difference between algorithms was marked by sex. Investigators should consider trade-offs between PPV and false negatives to identify patients with LEA using EMRs.

Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population

Fibrosis-4 (FIB-4) and the nonalcoholic fatty liver disease fibrosis score (NFS) are the 2 most popular noninvasive blood-based serum tests proposed for widespread fibrosis screening. We therefore aimed to describe the accuracy of FIB-4 and NFS to detect elevated liver stiffness as an indicator of hepatic fibrosis in low-prevalence populations. This study included a total of 5129 patients with concomitant measurement of FIB-4, NFS, and liver stiffness measurement (LSM) by Fibroscan (Echosens, France) from 5 independent population-based cohorts from Spain, Hong Kong, Denmark, England, and France; 3979 participants from the general population and 1150 from at-risk cohorts due to alcohol, diabetes, or obesity. We correlated LSM with FIB-4 and NFS, and calculated pre- and post-test predictive values of FIB-4 and NFS to detect elevated LSM at 8 kPa and 12 kPa cutoffs. The mean age was 53 ± 12 years, the mean body mass index was 27 ± 5 kg/m2, and 2439 (57%) were women. One in 10 patients (552; 11%) had liver stiffness ≥8 kPa, but 239 of those (43%) had a normal FIB-4, and 171 (31%) had normal NFS. The proportion of false-negatives was higher in at-risk patients than the general population. FIB-4 was false-negative in 11% of diabetic subjects, compared with 2.5% false-negatives with NFS. Waist circumference outperformed FIB-4 and NFS for detecting LSM ≥8 kPa in the general population. Almost one-third (28%-29%) of elevated FIB-4/NFS were false-positive in both the general population and at-risk cohorts. FIB-4 and NFS are suboptimal for screening purposes due to a high risk of overdiagnosis and a non-negligible percentage of false-negatives, especially in patients with risk factors for chronic liver disease. Waist circumference emerged as a potential first step to identify patients at risk for liver fibrosis in the general population.

Accuracy of self-assessment of gestational duration among people seeking abortion

Mifepristone, used together with misoprostol, is approved by the United States Food and Drug Administration for medication abortion through 10 weeks' gestation. Although in-person ultrasound is frequently used to establish medication abortion eligibility, previous research demonstrates that people seeking abortion early in pregnancy can accurately self-assess gestational duration using the date of their last menstrual period. In this study, we establish the screening performance of a broader set of questions for self-assessment of gestational duration among a sample of people seeking abortion at a wide range of gestations. We surveyed patients seeking abortion at 7 facilities before ultrasound and compared self-assessments of gestational duration using 11 pregnancy dating questions with measurements on ultrasound. For individual pregnancy dating questions and combined questions, we established screening performance focusing on metrics of diagnostic accuracy, defined as the area under the receiver operating characteristic curve, sensitivity (or the proportion of ineligible participants who correctly screened as ineligible for medication abortion), and proportion of false negatives (ie, the proportion of all participants who erroneously screened as eligible for medication abortion). We tested for differences in sensitivity across individual and combined questions using McNemar's test, and for differences in accuracy using the area under the receiver operating curve and Sidak adjusted P values. One-quarter (25%) of 1089 participants had a gestational duration of >70 days on ultrasound. Using the date of last menstrual period alone demonstrated 83.5% sensitivity (95% confidence interval, 78.4-87.9) in identifying participants with gestational durations of >70 days on ultrasound, with an area under the receiver operating characteristic curve of 0.82 (95% confidence interval, 0.79-0.85) and a proportion of false negatives of 4.0%. A composite measure of responses to questions on number of weeks pregnant, date of last menstrual period, and date they got pregnant demonstrated 89.1% sensitivity (95% confidence interval, 84.7-92.6) and an area under the receiver operating curve of 0.86 (95% confidence interval, 0.83-0.88), with 2.7% of false negatives. A simpler question set focused on being >10 weeks or >2 months pregnant or having missed 2 or more periods had comparable sensitivity (90.7%; 95% confidence interval, 86.6-93.9) and proportion of false negatives (2.3%), but with a slightly lower area under the receiver operating curve (0.82; 95% confidence interval, 0.79-0.84). In a sample representative of people seeking abortion nationally, broadening the screening questions for assessing gestational duration beyond the date of the last menstrual period resulted in improved accuracy and sensitivity of self-assessment at the 70-day threshold for medication abortion. Ultrasound assessment for medication abortion maynot be necessary, especially when requiring ultrasound could increase COVID-19 risk or healthcare costs, restrict access, or limit patient choice.

Generalizability and accuracy of IBM MarketScan health risk assessment instrument data for augmentation of commercial claims data.

We evaluated the generalizability and accuracy of the IBM® MarketScan® Health Risk Assessment (HRA) data to assess its suitability as supplement to linked claims data. We identified adult private insurance enrollees in the IBM® MarketScan® Commercial Claims & Encounters (CC&E) and HRA databases between 2012 and 2017. In the claims data, for each enrollee, we sampled the first calendar year with continuous enrollment indicating full capture of claims data and extracted linked HRA survey data if available. We compared HRA participants and non-participants considering demographics, prevalences of chronic conditions, and healthcare utilization. Including the subsample with HRA data only, we estimated the negative predictive value (NPV) of obesity and smoking reported in the HRA against diagnosis code in the claims data. Between 2012 and 2017, 2 693 444 and 31 450 000 of HRA and non-HRA participants were included in the study, respectively. Chronic diseases were similarly distributed between the two populations, with hypertension and hyperlipidemia representing the highest prevalence difference (1.4%). The two samples showed similar healthcare utilization. The proportion of false-negatives for obesity and smoking information when relying on the HRA data compared to patients with positive diagnosis based on claims data was low (<1%). Prevalence estimates of both variables were similar to national estimates. Our findings suggest that the overall HRA population may represent the overall claims population and HRA provides certain data elements with satisfactory accuracy.