RESUMEN
A prevalence boundary (PB) marks the point in prevalence in which the false omission rate, RFO = FN/(TN + FN), exceeds the tolerance limit for missed diagnoses. The objectives were to mathematically analyze rapid antigen test (RAgT) performance, determine why PBs are breeched, and evaluate the merits of testing three times over five days, now required by the US Food and Drug Administration for asymptomatic persons. Equations were derived to compare test performance patterns, calculate PBs, and perform recursive computations. An independent July 2023 FDA-NIH-university-commercial evaluation of RAgTs provided performance data used in theoretical calculations. Tiered sensitivity/specificity comprise the following: tier (1) 90%, 95%; tier (2) 95%, 97.5%; and tier (3) 100%, ≥99%. Repeating a T2 test improves the PB from 44.6% to 95.2% (RFO 5%). In the FDA-NIH-university-commercial evaluation, RAgTs generated a sensitivity of 34.4%, which improved to 55.3% when repeated, and then improved to 68.5% with the third test. With RFO = 5%, PBs are 7.37/10.46/14.22%, respectively. PB analysis suggests that RAgTs should achieve a clinically proven sensitivity of 91.0-91.4%. When prevalence exceeds PBs, missed diagnoses can perpetuate virus transmission. Repeating low-sensitivity RAgTs delays diagnosis. In homes, high-risk settings, and hotspots, PB breaches may prolong contagion, defeat mitigation, facilitate new variants, and transform outbreaks into endemic disease. Molecular diagnostics can help avoid these potential vicious cycles.
RESUMEN
This research uses mathematically derived visual logistics to interpret COVID-19 molecular and rapid antigen test (RAgT) performance, determine prevalence boundaries where risk exceeds expectations, and evaluate benefits of recursive testing along home, community, and emergency spatial care paths. Mathematica and open access software helped graph relationships, compare performance patterns, and perform recursive computations. Tiered sensitivity/specificity comprise: (T1) 90%/95%; (T2) 95%/97.5%; and (T3) 100%/≥99%, respectively. In emergency medicine, median RAgT performance peaks at 13.2% prevalence, then falls below T1, generating risky prevalence boundaries. RAgTs in pediatric ERs/EDs parallel this pattern with asymptomatic worse than symptomatic performance. In communities, RAgTs display large uncertainty with median prevalence boundary of 14.8% for 1/20 missed diagnoses, and at prevalence > 33.3−36.9% risk 10% false omissions for symptomatic subjects. Recursive testing improves home RAgT performance. Home molecular tests elevate performance above T1 but lack adequate validation. Widespread RAgT availability encourages self-testing. Asymptomatic RAgT and PCR-based saliva testing present the highest chance of missed diagnoses. Home testing twice, once just before mingling, and molecular-based self-testing, help avoid false omissions. Community and ER/ED RAgTs can identify contagiousness in low prevalence. Real-world trials of performance, cost-effectiveness, and public health impact could identify home molecular diagnostics as an optimal diagnostic portal.
RESUMEN
OBJECTIVE: To provide an estimation of the probability of error when chorionic villi (CV) cytogenetic analysis is limited to a single placental layer; either a direct preparation (Dir) or long-term culture (LTC). METHODS: We retrospectively reviewed cytogenetic studies on 81,593 consecutive CV samples in which both Dir and LTC were analyzed. All mosaic cases received amniocentesis. The false omission and false discovery rates were calculated by assessing the results that would have been reported when analysis was limited to either Dir or LTC. RESULTS: For all abnormalities combined, the proportion of normal Dir or LTC only reports that would have been inconsistent with a subsequent amniocentesis was 0.09% and 0.03%, respectively (false omissions). Among abnormal reports based on Dir or LTC alone, 8.01% and 3.17%, respectively, would be inconsistent with a subsequent amniocentesis result (false discoveries). Differences are present for individual abnormalities. CONCLUSIONS: From the perspective of identifying all abnormalities of potential clinical significance, the analysis of both placental layers is optimal. LTC alone is the preferred approach if only one layer of placenta is to be analyzed. Although rare, it is important to acknowledge that one cell layer analysis alone can cause misdiagnosis due to undetected mosaicism.